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Xultophy 100/3.6 insulin degludec and liraglutide 100 [iU]/mL; 3.6 mg/mL Injection, Solution — NDC 00169-2911-15 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

Xultophy 100/3.6 insulin degludec and liraglutide 100 [iU]/mL; 3.6 mg/mL Injection, Solution — NDC 0169-2911-15 (Billing 00169-2911-15)

by Novo Nordisk · 5 SYRINGE, PLASTIC in 1 CARTON / 3 mL in 1 SYRINGE, PLASTIC

This is a package of Xultophy 100/3.6 insulin degludec and liraglutide 100 [iU]/mL; 3.6 mg/mL Injection, Solution from Novo Nordisk, marketed since Nov 2016 and currently FDA-listed; retail pharmacies pay about $85.89 per mL (NADAC). It is this product's only package size.

NDC 00169-2911-15
🏷️ FDA NDC (as labeled) 0169-2911-15 billing pads the labeler segment with a zero
Rx only Brand On market Non-controlled ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 8, 2026 · this listing last changed Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

NDC database record

One package, one record: these facts belong to NDC 0169-2911-15 alone.

Record
FDA NDC Directory package listing · Human prescription drug
Code segments
0169 labeler · 2911 product · 15 package
Package marketed since
Nov 21, 2016
Sample package
No — commercial package
Listing certified through
Dec 31, 2026
Barcode (UPC-A, from the NDC)
3 0169291115 6
Medicaid fills, this package
568 prescriptions in the last four reported quarters
FDA record last changed
Jul 24, 2026

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 0169-2911-15
Product NDC 0169-2911
11-digit billing NDC 00169291115
NCPDP billing unit ML — per mL (volume)
RxCUI 1860167, 1860172
UNII 54Q18076QB, 839I73S42A
Application # BLA208583
SPL Set ID 21335fe4-d395-4501-ac2a-2f20d7520da9
Established class (EPC) Insulin Analog; GLP-1 Receptor Agonist
Mechanism of action Glucagon-like Peptide-1 (GLP-1) Agonists
Chemical class Insulin; Glucagon-Like Peptide 1
DEA schedule Non-controlled
Marketing category BLA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2016-11-21
Route SUBCUTANEOUS
Dosage form INJECTION, SOLUTION
Substance INSULIN DEGLUDEC; LIRAGLUTIDE
Biologic (Purple Book) 351(a)

Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification

GPI-14 2799100225D220
GPI class Xultophy
GCN Seq No 073919
GCN 38348
HICL code 041880
Ingredient (HICL) Insulin Degludec/Liraglutide
HIC1 code C
Therapeutic class — broad (HIC1) Electrolyte Balance/Metabolism/Nutrition
HIC2 code C4
Therapeutic class — intermediate (HIC2) Antihyperglycemics
HIC3 code C4X
Therapeutic class — specific (HIC3) Antihypergly,Insulin,Long Act-Glp-1 Recept.agonist
AHFS code 28:20.08.92
AHFS class Anorexigenic Agents, Miscellaneous
FDB label name XULTOPHY 100 UNIT-3.6MG/ML PEN
FDB brand name Xultophy 100-3.6
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 073919
  • GCN: 38348
  • GPI-14 (Medi-Span): 2799100225D220
  • HICL (First Databank): 041880
  • AHFS class code: 28:20.08.92
  • RxCUI (RxNorm): 1860167
Why two NDCs? The FDA registers this code as 0169-2911-15 — a 4-4-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the labeler segment → 00169-2911-15. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

RxNorm drug class

This medicine belongs to the Insulin Analog class.

Pharmacologic class Insulin Analog
Drug family (ATC) Insulins and analogues for injection, long-acting
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

Clinical

Label name XULTOPHY 100 UNIT-3.6MG/ML PEN Ingredient Insulin Degludec/Liraglutide
📖 What it is MedlinePlus · NLM

Insulin degludec is used to treat type 1 diabetes (condition in which the body does not produce insulin and therefore cannot control the amount of sugar in the blood). It is also used to treat people with type 2 diabetes (condition in which the body does not use insulin normally and, therefore, cannot control the amount of sugar in the blood) who need insulin to control their diabetes. In patients with type 1 diabetes, insulin degludec must be used with another type of insulin (a short-acting insulin). In patients with type 2 diabetes, insulin degludec may be used with another type of insulin...

Read the full MedlinePlus article ↗

Supplement & herbal interactions

🌿 Drug–supplement interaction checker →
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

Pricing

A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.

Price systemPer mLPer package
Retail pharmacies payNADAC · weekly $85.886 $1,288.28 / 15 ml
Medicaid paysCMS SDUD · 12 mo $86.30 $1,294.54 / 15 ml
Medicare drug plans payPart D · Q2 2026 $85.83 $1,287.41 / 15 ml
NADAC price history (per mL) — tap or hover for the price & month
Oct 2021 Dec 2025 May 2026 Sep 2026 $85.909 $73.486
▲ Up 17% over the last 13 months.
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
00169-2911-15 You're viewing this Main listing 5 SYRINGE, PLASTIC in 1 CARTON / 3 mL in 1 SYRINGE, PLASTIC 2016-11-21 — Active

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Xultophy 100/3.6 100 [iU]/mL; 3.6 mg/mLthis 00169-2911-15 Novo 5 syringes $85.886 — Availability likely —
About this product: this is a biologic. Biologics don't have small-molecule generics — competition comes from FDA-licensed biosimilars (shown above), not generics.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & biosimilar status

🏛️
2016
First FDA approval
Nov 2016
📍
2026
Currently FDA-listed
10 years listed
🛡️
2028
Latest patent/protection listed
not a guaranteed launch date
🧬Biologic — competition comes from biosimilars

Biologics have no small-molecule generics; biosimilar competition is tracked in the FDA Purple Book.

🛡️ Latest patent/protection date listed: FDA patent/protection data lists protections through Nov 2028. This may affect when biosimilars become widely available, but it is not a guaranteed launch date.
📅 FDA approved Nov 21, 2016 ⏳ ~2.1 yr to latest listed protection

Why the date isn’t exact: Biosimilar timing can change because patents may be challenged, settled, licensed, added or removed, and litigation can move the real date earlier or later.

FDA Purple Book — biosimilars & interchangeables ⓘ
Reference product
Xultophy 100/3.6insulin degludec and liraglutide
🔒 No FDA-licensed biosimilars or interchangeable biosimilars are listed yet for this biologic. It currently has no biosimilar competition in the FDA Purple Book.
Source: FDA Purple Book (purplebooksearch.fda.gov), matched on the reference product’s active ingredient.
Patents & exclusivity — FDA Purple Book
Exclusivity RefProduct
2016 2018 2020 2022 2024 2026 2028
Today
LOE
Biologic patent Exclusivity
🏛️Reference-product exclusivity
A flat 12 years of FDA market protection from first licensure. No biosimilar can be licensed before it ends — regardless of patents.
🧪Listed biologic patents
Patents the reference maker lists covering the molecule, formulation, or manufacturing. A biosimilar generally can’t launch until these resolve.
🔁Interchangeability
An interchangeable biosimilar may be substituted at the pharmacy (state laws vary). The first one can earn its own exclusivity period.
🛈 What do these terms mean?
Biologic patent
A patent the reference product’s maker has publicly listed. A biosimilar generally can’t launch until these expire — unless they’re invalidated or resolved in a settlement.
Reference-product exclusivity
A flat 12 years of FDA market protection from the biologic’s first licensure (the BPCIA). No biosimilar can be licensed before it ends, regardless of patents.
Interchangeable exclusivity
The first interchangeable biosimilar can earn a period as the only interchangeable version (pharmacists can substitute it without the prescriber).
Earliest biosimilar (LOE)
The latest of all the dates above — the soonest a biosimilar can realistically reach the market. Litigation and settlements can move it earlier.

Biologics have no small-molecule “generics” — competition comes from FDA-licensed biosimilars, tracked in the FDA Purple Book.

FDA exclusivity
CodeWhat it grantsExpires
RefProductReference-product exclusivity (12-year, BPCIA) — no biosimilar can be licensed before this dateNov 21, 2028
Common questions
Is there a biosimilar for XULTOPHY 100 UNIT-3.6MG/ML PEN?
No FDA-licensed biosimilar is currently listed for this biologic in the FDA Purple Book.
Why do different websites show different biosimilar dates?
Biosimilar availability isn’t based on one single date. Some sources use the reference-product exclusivity, some use the last listed patent, and patent litigation, settlements, and licenses can all change the real-world launch date. This page shows the underlying Purple Book dates so you can see why estimates differ.
Can a biosimilar launch before the last patent expires?
Sometimes. A biosimilar maker may settle with the reference manufacturer or receive a license to launch earlier. In other cases, the last listed protection delays competition.
What does “current Purple Book estimate” mean?
It means we’re using the latest patent and exclusivity dates currently listed in the FDA Purple Book. It is not a guaranteed launch date.
What does “FDA listed” mean?
It means the product appears in the FDA’s official directory. That’s a good sign a product exists for the U.S. market, but on its own it does not confirm a pharmacy can get it today. Where we have recent retail pricing data, we label it “Availability likely” instead.
What does a patent or protection date mean here?
It’s the latest date currently listed in the FDA Purple Book for a patent or exclusivity on the reference biologic. It can affect when a biosimilar becomes widely available — but it is not a guaranteed launch date. Settlements and licenses can move the real date earlier or later.
Built from the FDA Purple Book Patent List (patents the reference-product sponsor has publicly listed under the BPCIA) plus reference-product exclusivity. Biosimilars cannot launch until these clear; patent litigation and settlements can shift the real date. Biologics have no small-molecule generics — competition comes from FDA-licensed biosimilars, not the Orange Book.
Where does this data come from?
Patents and exclusivity from the FDA Purple Book (biologics), refreshed from public FDA data. Biosimilar launch timing is an estimate, not a guarantee.

Inactive Ingredients / Excipients

Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.

💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.

  • 19.7 mg / 1 mL UNII PDC6A3C0OX
    Glycerin is a clear, thick liquid derived from plant oils or fats. It acts as a humectant to retain moisture, a sweetener, and a solvent in medications.
  • 5.70 mg / 1 mL UNII 339NCG44TV
    Phenol is a chemical compound derived from coal tar or petroleum. It serves as a preservative and antimicrobial agent in medicines, helping prevent bacterial and fungal growth to keep the product stable and safe during storage.
  • UNII 059QF0KO0R
    Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.
  • 55 ug / 1 mL UNII J41CSQ7QDS
    A mineral element that strengthens tablet structure and acts as a processing aid. Zinc helps bind ingredients together and may improve the medicine's stability during manufacturing and storage.

4 inactive ingredients listed in the exact product block matched to this NDC.

Where does this data come from?
Data sourced from official FDA Structured Product Labeling (SPL) via DailyMed — ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.

Inactive ingredient FAQ

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

Manufacturer & labeler

LabelerNovo Nordisk
FDA applicationBLA208583 (BLA)
Labeler code00169
First marketedNov 2016
Product typeHuman Prescription Drug
Portfolio74 products on file

More NDCs from Novo Nordisk labeler code 00169

The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Very long sections are excerpted here and marked; the full text is on DailyMed (linked in the sources below). Jump with a chip, search within the label, or expand everything.
🚨 Boxed Warning 🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients 💬 Medication Guide 🧬 Pharmacokinetics 🧬 Pharmacodynamics 🔬 Clinical Studies 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📄 Recent Major Changes 📄 Package Label / Principal Display Panel
🚨 Boxed Warning ~1 min read ▾

WARNING: RISK OF THYROID C-CELL TUMORS • Liraglutide, one of the components of XULTOPHY 100/3.6, causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures in both genders of rats and mice. It is unknown whether XULTOPHY 100/3.6 causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of liraglutide-induced rodent thyroid C-cell tumors has not been determined [see Warnings and Precautions ( 5.1 ), Nonclinical Toxicology ( 13 )] . • XULTOPHY 100/3.6 is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).

Counsel patients regarding the potential risk for MTC with the use of XULTOPHY 100/3.6 and inform them of symptoms of thyroid tumors (e.g., a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with XULTOPHY 100/3.6 [see Contraindications ( 4 ), Warnings and Precautions ( 5.1 )] . WARNING: RISK OF THYROID C-CELL TUMORS See full prescribing information for complete boxed warning. • Liraglutide, one of the components of XULTOPHY 100/3.6, causes thyroid C-cell tumors at clinically relevant exposures in both genders of rats and mice.

It is unknown whether XULTOPHY 100/3.6 causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of liraglutide-induced rodent thyroid C-cell tumors has not been determined. ( 5.1 , 13.1 ) • XULTOPHY 100/3.6 is contraindicated in patients with a personal or family history of MTC or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk of MTC and the symptoms of thyroid tumors.

( 4 , 5.1 )

🎯 Indications and Usage 173 words ▾

1 INDICATIONS AND USAGE XULTOPHY 100/3.6 is a combination of insulin degludec and liraglutide and is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Limitations of Use: • XULTOPHY 100/3.6 contains liraglutide. Coadministration with any other product containing liraglutide or another glucagon-like peptide-1 (GLP-1) receptor agonist is not recommended [see Warnings and Precautions ( 5.5 )]. • XULTOPHY 100/3.6 is not recommended for the treatment of diabetic ketoacidosis. • XULTOPHY 100/3.6 has not been studied in combination with prandial insulin.

XULTOPHY 100/3.6 is a combination of insulin degludec, a long-acting human insulin analog, and liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Limitations of Use : ( 1 ) • Coadministration with any other product containing liraglutide or another GLP-1 receptor agonist is not recommended. • Not recommended for the treatment of diabetic ketoacidosis. • Has not been studied in combination with prandial insulin.

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION • Administer once-daily at same time each day with or without food. ( 2.1 ) • XULTOPHY 100/3.6 pen delivers doses from 10 to 50 units with each injection ( 2.1 , 2.2 ); each XULTOPHY 100/3.6 dosage unit contains 1 unit of insulin degludec and 0.036 mg of liraglutide. ( 2.1 ) • Maximum daily dosage is 50 units (50 units of insulin degludec and 1.8 mg of liraglutide).

( 2.1 ) • Recommended starting dosage in patients naïve to basal insulin or GLP-1 receptor agonist is 10 units (10 units of insulin degludec and 0.36 mg of liraglutide) injected subcutaneously once-daily. (2.2 ) • Discontinue therapy with liraglutide or basal insulin prior to initiation of XULTOPHY 100/3.6. ( 2.2 ) • Recommended starting dosage in patients currently on basal insulin or GLP-1 receptor agonist is 16 units (16 units of insulin degludec and 0.58 mg of liraglutide) injected subcutaneously once-daily.

( 2.2 ) • See Full Prescribing Information for titration recommendations. ( 2.3 ) • Inject XULTOPHY 100/3.6 subcutaneously into the thigh, upper arm, or abdomen. ( 2.5 ) • Rotate injection sites to reduce risk of lipodystrophy and localized cutaneous amyloidosis.

( 2.5 ) • Do not administer intravenously or by an infusion pump. ( 2.5 ) • Do not dilute or mix with any other insulin products or solutions. ( 2.5 )

2.1Important Dosage Information • XULTOPHY 100/3.6 is a combination of insulin degludec and liraglutide. • Administer XULTOPHY 100/3.6 by subcutaneous injection once-daily at the same time each day with or without food. • The XULTOPHY 100/3.6 pen delivers doses from 10 to 50 units with each injection. Table 1 presents the units of insulin degludec and the milligrams of liraglutide in each dosage of XULTOPHY 100/3.6 [see Dosage and Administration ( 2.2 )]. • The maximum dosage of XULTOPHY 100/3.6 is 50 units daily (50 units of insulin degludec and 1.8 mg of liraglutide) [see Warnings and Precautions ( 5.5 )] .

2.2Recommended Starting Dosage In patients naïve to basal insulin or a GLP-1 receptor agonist • The recommended starting dosage of XULTOPHY 100/3.6 is 10 units (10 units of insulin degludec and 0.36 mg of liraglutide) injected subcutaneously once-daily (see Table 1 ). In patients currently on basal insulin or a GLP-1 receptor agonist • Discontinue therapy with basal insulin or GLP-1 receptor agonist prior to initiation of XULTOPHY 100/3.6. • The recommended starting dosage of XULTOPHY 100/3.6 is 16 units (16 units of insulin degludec and 0.58 mg of liraglutide) injected subcutaneously once-daily (see Table 1 ).

Table 1. Units of Insulin Degludec and Milligrams of Liraglutide in Each Dosage of XULTOPHY 100/3.6 XULTOPHY 100/3.6 (dose counter display) * insulin degludec component dose liraglutide component dose Comment ▪▪ ─ --- --- Priming symbol 10 10 units 0.36 mg Recommended starting dose for patients naïve to basal insulin or GLP-1 receptor agonist 11 11 units 0.4 mg 12 12 units 0.43 mg 13 13 units 0.47 mg 14 14 units 0.5 mg 15 15 units 0.54 mg 16 16 units 0.58 mg Recommended starting dose for patients currently on basal insulin or GLP-1 receptor agonist 17 17 units 0.61 mg 18 18 units 0.65 mg 19 19 units 0.68 mg 20 20 units 0.72 mg 21 21 units 0.76 mg 22 22 units 0.79 mg 23 23 units 0.83 mg 24 24 units 0.86 mg 25 25 units 0.9 mg 26 26 units 0.94 mg 27 27 units 0.97 mg 28 28 units 1.01 mg 29 29 units 1.04 mg 30 30 units 1.08 mg 31 31 units 1.12 mg 32 32 units 1.15 mg 33 33 units 1.19 mg 34 34 units 1.22 mg 35 35 units 1.26 mg 36 36 units 1.3 mg 37 37 units 1.33 mg 38 38 units 1.37 mg 39 39 units 1.4 mg 40 40 units 1.44 mg 41 41 units 1.48 mg 42 42 units 1.51 mg 43 43 units 1.55 mg 44 44 units 1.58 mg 45 45 units 1.62 mg 46 46 units 1.66 mg 47 47 units 1.69 mg 48 48 units 1.73 mg 49 49 units 1.76 mg 50 50 units 1.8 mg Maximum daily dosage [see Warnings and Precautions (5.5)] * The dose counter on the XULTOPHY 100/3.6 pen displays numbers for the even units and displays lines for the odd units.

2.3Titration of XULTO… [Excerpted — this section continues on DailyMed.]

💊 Dosage Forms and Strengths 50 words ▾

3 DOSAGE FORMS AND STRENGTHS Injection: 100 units/mL insulin degludec and 3.6 mg/mL liraglutide available as a clear, colorless solution in a 3 mL prefilled, disposable, single-patient-use pen injector. Injection: 100 units/mL of insulin degludec and 3.6 mg/mL of liraglutide available in: • 3 mL single-patient-use pen. ( 3 )

⛔ Contraindications 152 words ▾

4 CONTRAINDICATIONS XULTOPHY 100/3.6 is contraindicated: • In patients with a personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) [see Warnings and Precautions ( 5.1 )] . • During episodes of hypoglycemia [see Warnings and Precautions ( 5.6 )] . • In patients with hypersensitivity to insulin degludec, liraglutide, or any of the excipients in XULTOPHY 100/3.6. Serious hypersensitivity reactions including anaphylactic reactions and angioedema have been reported with liraglutide, one of the components of XULTOPHY 100/3.6 [see Warnings and Precautions ( 5.9 )]. • Patients with a personal or family history of medullary thyroid carcinoma or in patients with Multiple Endocrine Neoplasia syndrome type 2 ( 4 ) • During episodes of hypoglycemia ( 4 ) • Patients with a serious hypersensitivity reaction to insulin degludec, liraglutide, or any of the excipients in XULTOPHY 100/3.6 ( 4 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS • Acute Pancreatitis : Has been observed in patients treated with GLP-1 receptor agonists, including liraglutide. Discontinue if pancreatitis is suspected. ( 5.2 ) • Never share a XULTOPHY 100/3.6 pen between patients, even if the needle is changed.

( 5.3 ) • Hyperglycemia or hypoglycemia with changes in insulin regimen : Make changes to a patient’s insulin regimen (e.g., insulin strength, manufacturer, type, injection site or method of administration) under close medical supervision with increased frequency of blood glucose monitoring. ( 5.4 ) • Overdose due to medication errors : XULTOPHY 100/3.6 contains two drugs. Instruct patients to check label before injection since accidental mix-ups with insulin containing products can occur.

Do not exceed the maximum dose or administer with other GLP-1 receptor agonists. ( 5.5 ) • Hypoglycemia: May be life-threatening. Increase monitoring with changes to : dosage, concomitant drugs, meal pattern, physical activity; and in patients with renal impairment or hepatic impairment or hypoglycemia unawareness.

( 5.6 ) • Acute Kidney Injury Due to Volume Depletion : Monitor renal function in patients reporting adverse reactions that could lead to volume depletion. ( 5.7 ) • Severe Gastrointestinal Adverse Reactions : Use has been associated with gastrointestinal adverse reactions, sometimes severe. XULTOPHY 100/3.6 is not recommended in patients with severe gastroparesis.

( 5.8 ) • Hypersensitivity Reactions : Severe, life-threatening, generalized allergy, including anaphylaxis, angioedema, bronchospasm, hypotension, and shock can occur. If a hypersensitivity reaction occurs, discontinue and treat per standard of care. ( 5.9 ) • Acute Gallbladder Disease : If cholelithiasis or cholecystitis are suspected, gallbladder studies are indicated.

( 5.10 ) • Hypokalemia : May be life-threatening. Monitor potassium levels in patients at risk for hypokalemia and treat if indicated. ( 5.11 ) • Fluid retention and congestive heart failure with use of thiazolidinediones (TZDs) : Observe for signs and symptoms of heart failure; consider dosage reduction or discontinuation if heart failure occurs.

( 5.12 ) • Pulmonary Aspiration During General Anesthesia or Deep Sedation : Has been reported in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures. Instruct patients to inform healthcare providers of any planned surgeries or procedures. ( 5.13 )

5.1Risk of Thyroid C-cell Tumors Liraglutide, one of the components of XULTOPHY 100/3.6, causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors (adenomas and/or carcinomas) at clinically relevant exposures in both genders of rats and mice [see Nonclinical Toxicology ( 13.1 )] . Malignant thyroid C-cell carcinomas were detected in rats and mice. It is unknown whether XULTOPHY 100/3.6 will cause thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of liraglutide-induced rodent thyroid C-cell tumors has not been determined.

Cases of MTC in patients treated with liraglutide have been reported in the postmarketing period; the data in these reports are insufficient to establish or exclude a causal relationship between MTC and liraglutide use in humans. XULTOPHY 100/3.6 is contraindicated in patients with a personal or family history of MTC or in patients with MEN 2. Counsel patients regarding the potential risk for MTC with the use of XULTOPHY 100/3.6 and inform them of symptoms of thyroid tumors (e.g., a mass in the neck, dysphagia, dyspnea, persistent hoarseness).

Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with XULTOPHY 100/3.6. Such monitoring may increase the risk of unnecessary procedures, due to low test specificity for serum calcitonin and a high background incidence of thyroid disease. Significantly elevated serum calcitonin may indicate MTC and… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The following serious adverse reactions are described below or elsewhere in the prescribing information: • Risk of Thyroid C-cell Tumors [see Warnings and Precautions ( 5.1 )] • Acute Pancreatitis [see Warnings and Precautions ( 5.2 )] • Hypoglycemia [see Warnings and Precautions ( 5.6 )] • Acute Kidney Injury Due to Volume Depletion [see Warnings and Precautions ( 5.7 )] • Severe Gastrointestinal Adverse Reactions [see Warnings and Precautions ( 5.8 )] • Hypersensitivity Reactions [see Warnings and Precautions ( 5.9 )] • Acute Gallbladder Disease [see Warnings and Precautions ( 5.10 )] • Hypokalemia [see Warnings and Precautions ( 5.11 )] • Pulmonary Aspiration During General Anesthesia or Deep Sedation [see Warnings and Precautions ( 5.13 )] • Most common adverse reactions (incidence ≥5%) in clinical trials are nasopharyngitis, headache, nausea, diarrhea, increased lipase and upper respiratory tract infection.

( 6 ) • Immunogenicity-related events, including urticaria, were more common among liraglutide-treated patients (0.8%) than among comparator-treated patients (0.4%) in clinical trials. ( 12.6 ) To report SUSPECTED ADVERSE REACTIONS, contact Novo Nordisk Inc. at 1-800-727-6500 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. XULTOPHY 100/3.6 The data in Table 3 reflect the exposure of 1881 patients to XULTOPHY 100/3.6 and a mean duration of exposure of 33 weeks in trials NCT01336023, NCT01618162, NCT02773368, NCT01676116, NCT01392573, NCT01952145 [see Clinical Studies ( 14.2 and 14.3 )] .

The mean age was 57 years and 3% were older than 75 years; 53% were male, 75% were White, 6% were Black or African American and 16% were Hispanic or Latino. The mean body mass index (BMI) was 31.8 kg/m 2 . The mean duration of diabetes was 9 years and the mean HbA 1c at baseline was 8.2%.

A history of neuropathy, ophthalmopathy, nephropathy and cardiovascular disease at baseline was reported in 25%, 12%, 7% and 6% respectively. The mean estimated glomerular filtration rate (eGFR) at baseline was 88.3 mL/min/1.73 m 2 and 6% of the patients had an eGFR less than 60 mL/min/1.73 m 2 . Table 3: Adverse Reactions Occurring in ≥5% of XULTOPHY 100/3.6-Treated Patients with Type 2 Diabetes Mellitus XULTOPHY 100/3.6 N = 1881 % Nasopharyngitis 10 Headache 9 Nausea 8 Diarrhea 8 Increased Lipase 7 Upper respiratory tract infection 6 Hypoglycemia Hypoglycemia was the most commonly observed adverse reaction in patients treated with insulin and insulin containing products, including XULTOPHY 100/3.6 [see Warnings and Precautions ( 5.6 )].

The number of reported hypoglycemia episodes depended on the definition of hypoglycemia used, insulin dose, intensity of glucose control, background therapies, and other intrinsic and extrinsic patient factors. For these reasons, comparing rates of hypoglycemia in clinical trials for XULTOPHY 100/3.6 with the incidence of hypoglycemia for other products may be misleading and also, may not be representative of hypoglycemia rates that will occur in clinical practice. In the phase 3 clinical program [see Clinical Studies ( 14 )] , events of severe hypoglycemia were defined as an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions ( Table 4 ).

Hypoglycemia episodes with a glucose level below 54 mg/dL associated with or without symptoms is shown in Table 4 . No clinically important differences in risk of severe hypoglycemia between XULTOPHY 100/3.6 and comparators were observed in clinical trials. Table 4.

Hypoglycemia Episodes Reported in XULTOPHY 100/3.6-Treated Patients with T2DM † Episode requiring assistance of another person to activel… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions ~2 min read ▾

7 DRUG INTERACTIONS • Drugs that affect glucose metabolism : Adjustment of XULTOPHY 100/3.6 dosage may be needed; closely monitor blood glucose. ( 7.1 ) • Anti-Adrenergic drugs (e.g., beta-blockers, clonidine, guanethidine, and reserpine): Hypoglycemia signs and symptoms may be reduced or absent. ( 7.1 ) • Effects of delayed gastric emptying on oral medications : May impact absorption of concomitantly administered oral medications. ( 7.2 )

7.1Medications that Can Affect Glucose Metabolism A number of medications affect glucose metabolism and may require dose adjustment of XULTOPHY 100/3.6 and particularly close monitoring [see Dosage and Administration ( 2.2 ), Warnings and Precautions ( 5.6 )]. Drugs That May Increase the Risk of Hypoglycemia Drugs: Antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analogs (e.g., octreotide), and sulfonamide antibiotics Intervention: Dosage reductions and increased frequency of glucose monitoring may be required when XULTOPHY 100/3.6 is coadministered with these drugs.

Drugs That May Decrease the Blood Glucose Lowering Effect of XULTOPHY 100/3.6 Drugs: Atypical antipsychotics (e.g., olanzapine and clozapine), corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), and thyroid hormones. Intervention: Dosage increases and increased frequency of glucose monitoring may be required when XULTOPHY 100/3.6 is coadministered with these drugs.

Drugs That May Increase or Decrease the Blood Glucose Lowering Effect of XULTOPHY 100/3.6 Drugs: Alcohol, beta-blockers, clonidine, and lithium salts. Pentamidine may cause hypoglycemia, which may sometimes be followed by hyperglycemia. Intervention: Dosage adjustment and increased frequency of glucose monitoring may be required when XULTOPHY 100/3.6 is coadministered with these drugs.

Drugs That May Blunt Signs and Symptoms of Hypoglycemia Drugs: Beta-blockers, clonidine, guanethidine, and reserpine Intervention: Increased frequency of glucose monitoring may be required when XULTOPHY 100/3.6 is coadministered with these drugs.

7.2Effects of Delayed Gastric Emptying on Oral Medications Liraglutide-containing products, including XULTOPHY 100/3.6, cause a delay of gastric emptying, and thereby have the potential to impact the absorption of concomitantly administered oral medications. In clinical pharmacology trials, liraglutide did not affect the absorption of the tested orally administered medications to any clinically relevant degree [see Clinical Pharmacology ( 12.3 )] . Nonetheless, caution should be exercised when oral medications are concomitantly administered with liraglutide containing products.

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS Pregnancy: XULTOPHY 100/3.6 should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. ( 8.1 )

8.1Pregnancy Risk Summary Based on animal reproduction studies, there may be risks to the fetus from exposure to liraglutide during pregnancy. XULTOPHY 100/3.6 should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. There are no available data with XULTOPHY 100/3.6, insulin degludec or liraglutide in pregnant women to inform a drug associated risk for major birth defects and miscarriage.

There are clinical considerations regarding the risks of poorly controlled diabetes in pregnancy (see Clinical Considerations). For insulin degludec, rats and rabbits were exposed in animal reproduction studies at 5 times (rat) and 10 times (rabbit) the human exposure at a dose of

0.75U/kg/day. No adverse outcomes were observed for pregnant animals and offspring (see Data) . For liraglutide, animal reproduction studies identified increased adverse developmental outcomes from exposure during pregnancy.

Liraglutide exposure was associated with early embryonic deaths and an imbalance in some fetal abnormalities in pregnant rats administered liraglutide during organogenesis at doses that approximate clinical exposures at the maximum recommended human dose (MRHD) of 1.8 mg/day. In pregnant rabbits administered liraglutide during organogenesis, decreased fetal weight and an increased incidence of major fetal abnormalities were seen at exposures below the human exposures at the MRHD (see Data) . In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

The estimated background risk of major birth defects is 6 to 10% in women with pregestational diabetes with a peri-conceptional HbA 1c >7 and has been reported to be as high as 20 to 25% in women with a peri-conceptional HbA 1c >10. The estimated background risk of miscarriage for the indicated population is unknown. Clinical Considerations Disease-Associated Maternal and/or Embryo/fetal Risk Hypoglycemia and hyperglycemia occur more frequently during pregnancy in patients with pre-gestational diabetes.

Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes mellitus increases the fetal risk for major birth defects, stillbirth, macrosomia related morbidity. Data Animal Data Insulin degludec Insulin degludec was investigated in studies covering fertility, embryo-fetal development and pre- and post-natal development in rats and during the period of embryo-fetal development in rabbits.

Human insulin (NPH insulin) was included as comparator. In these studies insulin degludec was given subcutaneously at up to 21 U/kg/day in rats and

3.3U/kg/day in rabbits, resulting in 5 times (rat) and 10 times (rabbit) the human exposure (AUC) at a human subcutaneous dose of

0.75U/kg/day. Overall the effects of insulin degludec were similar to those observed with human insulin. Liraglutide Female rats given subcutaneous doses of 0.1, 0.25 and 1.0 mg/kg/day liraglutide beginning 2 weeks before mating through gestation day 17 had estimated systemic exposures 0.8-, 3-, and 11-times the human exposure at the MRHD based on plasma AUC comparison.

The number of early embryonic deaths in the 1 mg/kg/day group increased slightly. Fetal abnormalities and variations in kidneys and blood vessels, irregular ossification of the skull, and a more complete state of ossification occurred at all doses. Mottled liver and minimally kinked ribs occurred at the highest dose.

The incidence of fetal malformations in liraglutide-treated groups exceeding concurrent and historical controls were misshapen oropharynx and/or narrowed opening into larynx at 0.1 mg/kg/d… [Excerpted — this section continues on DailyMed.]

🤰 Pregnancy ~3 min read ▾

8.1Pregnancy Risk Summary Based on animal reproduction studies, there may be risks to the fetus from exposure to liraglutide during pregnancy. XULTOPHY 100/3.6 should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. There are no available data with XULTOPHY 100/3.6, insulin degludec or liraglutide in pregnant women to inform a drug associated risk for major birth defects and miscarriage.

There are clinical considerations regarding the risks of poorly controlled diabetes in pregnancy (see Clinical Considerations). For insulin degludec, rats and rabbits were exposed in animal reproduction studies at 5 times (rat) and 10 times (rabbit) the human exposure at a dose of

0.75U/kg/day. No adverse outcomes were observed for pregnant animals and offspring (see Data) . For liraglutide, animal reproduction studies identified increased adverse developmental outcomes from exposure during pregnancy.

Liraglutide exposure was associated with early embryonic deaths and an imbalance in some fetal abnormalities in pregnant rats administered liraglutide during organogenesis at doses that approximate clinical exposures at the maximum recommended human dose (MRHD) of 1.8 mg/day. In pregnant rabbits administered liraglutide during organogenesis, decreased fetal weight and an increased incidence of major fetal abnormalities were seen at exposures below the human exposures at the MRHD (see Data) . In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

The estimated background risk of major birth defects is 6 to 10% in women with pregestational diabetes with a peri-conceptional HbA 1c >7 and has been reported to be as high as 20 to 25% in women with a peri-conceptional HbA 1c >10. The estimated background risk of miscarriage for the indicated population is unknown. Clinical Considerations Disease-Associated Maternal and/or Embryo/fetal Risk Hypoglycemia and hyperglycemia occur more frequently during pregnancy in patients with pre-gestational diabetes.

Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes mellitus increases the fetal risk for major birth defects, stillbirth, macrosomia related morbidity. Data Animal Data Insulin degludec Insulin degludec was investigated in studies covering fertility, embryo-fetal development and pre- and post-natal development in rats and during the period of embryo-fetal development in rabbits.

Human insulin (NPH insulin) was included as comparator. In these studies insulin degludec was given subcutaneously at up to 21 U/kg/day in rats and

3.3U/kg/day in rabbits, resulting in 5 times (rat) and 10 times (rabbit) the human exposure (AUC) at a human subcutaneous dose of

0.75U/kg/day. Overall the effects of insulin degludec were similar to those observed with human insulin. Liraglutide Female rats given subcutaneous doses of 0.1, 0.25 and 1.0 mg/kg/day liraglutide beginning 2 weeks before mating through gestation day 17 had estimated systemic exposures 0.8-, 3-, and 11-times the human exposure at the MRHD based on plasma AUC comparison.

The number of early embryonic deaths in the 1 mg/kg/day group increased slightly. Fetal abnormalities and variations in kidneys and blood vessels, irregular ossification of the skull, and a more complete state of ossification occurred at all doses. Mottled liver and minimally kinked ribs occurred at the highest dose.

The incidence of fetal malformations in liraglutide-treated groups exceeding concurrent and historical controls were misshapen oropharynx and/or narrowed opening into larynx at 0.1 mg/kg/day and umbilical hernia at 0.1 and 0.25 mg/kg/day. Pregnant rabbits given subcutaneous doses of 0.01, 0.025 and 0.05 mg/kg/day liraglutide from gestation day 6 through day… [Excerpted — this section continues on DailyMed.]

🧒 Pediatric Use 16 words ▾

8.4Pediatric Use Safety and effectiveness of XULTOPHY 100/3.6 have not been established in pediatric patients.

🧓 Geriatric Use 110 words ▾

8.5Geriatric Use Of the total number of 1,881 subjects in clinical studies of XULTOPHY 100/3.6, 375 (19.9%) were 65 years and over, while 52 (2.8%) were 75 years and over [see Clinical Studies ( 14 )] . No overall differences in safety or effectiveness of XULTOPHY 100/3.6 were observed between patients 65 years of age and older and younger patients. Age had no clinically relevant effect on the pharmacokinetics of XULTOPHY 100/3.6 [see Clinical Pharmacology ( 12.3 )] .

In geriatric patients with diabetes, the initial dosing, dose increments, and maintenance dosage should be conservative to avoid hypoglycemic reactions. Hypoglycemia may be more difficult to recognize in geriatric patients.

🆘 Overdosage 198 words ▾

10 OVERDOSAGE Hypoglycemia (from insulin and liraglutide) and gastrointestinal adverse reactions (from liraglutide) may develop if a patient is dosed with more XULTOPHY 100/3.6 than required. An excess of insulin-containing products like XULTOPHY 100/3.6 relative to food intake, energy expenditure, or both may lead to severe and sometimes prolonged and life-threatening hypoglycemia and hypokalemia [see Warnings and Precautions ( 5.6 , 5.10 )] . Mild episodes of hypoglycemia usually can be treated with oral glucose.

Lowering the drug dosage, and adjustments in meal patterns, or exercise may be needed. More severe episodes of hypoglycemia with coma, seizure, or neurologic impairment may be treated with intramuscular/subcutaneous glucagon for emergency use or concentrated intravenous glucose. After apparent clinical recovery from hypoglycemia, continued observation and additional carbohydrate intake may be necessary to avoid reoccurrence of hypoglycemia.

Hypokalemia must be corrected appropriately. Overdoses have been reported in clinical trials and postmarketing use of liraglutide, one of the components of XULTOPHY 100/3.6. Effects have included severe nausea and severe vomiting.

In the event of overdosage, consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdosage management recommendations. Initiate appropriate supportive treatment according to the patient’s clinical signs and symptoms.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action XULTOPHY 100/3.6 XULTOPHY 100/3.6 is a combination product consisting of insulin degludec and liraglutide. Insulin degludec The primary activity of insulin degludec is the regulation of glucose metabolism. Insulin and its analogs lower blood glucose by stimulating peripheral glucose uptake, especially by skeletal muscle and fat, and by inhibiting hepatic glucose production.

Insulin also inhibits lipolysis and proteolysis, and enhances protein synthesis. Liraglutide Liraglutide is a GLP-1 receptor agonist that increases glucose-dependent insulin release, decreases glucagon secretion, and slows gastric emptying.

12.2Pharmacodynamics Following a single-dose administration, XULTOPHY 100/3.6 has a duration of action reflecting the combination of the individual glucodynamic action profiles of insulin degludec and liraglutide. Following once-daily administration, XULTOPHY 100/3.6 lowers fasting plasma glucose levels and postprandial glucose levels. Cardiac Electrophysiology (QTc): XULTOPHY 100/3.6 The effect of XULTOPHY 100/3.6 on QTc has not been studied.

Liraglutide The effect of liraglutide, one of the components of XULTOPHY 100/3.6, on cardiac repolarization was tested in a QTc study. Liraglutide, at steady state concentrations with daily doses up to 1.8 mg, did not produce QTc prolongation.

12.3Pharmacokinetics Overall, the pharmacokinetics of insulin degludec and liraglutide were not affected in a clinically relevant manner when administered as XULTOPHY 100/3.6. Absorption In patients with type 2 diabetes mellitus (mean body weight 87.5 kg) reaching the maximum daily dose (50 units/1.8 mg) of XULTOPHY 100/3.6, the estimated mean steady-state exposure (AUC 0-24 h) of insulin degludec was 113 h*nmol/L and of liraglutide 1227 h*ng/mL based on population pharmacokinetic analysis. The corresponding maximum concentrations were 5196 pmol/L for insulin degludec and 55 ng/mL for liraglutide.

Steady state concentrations of insulin degludec and liraglutide are reached after 2-3 days of daily administration. Distribution Insulin degludec and liraglutide are extensively bound to plasma proteins >99% and >98%, respectively. Elimination The half-life of insulin degludec is approximately 25 hours and the half-life of liraglutide is approximately 13 hours.

Metabolism Insulin degludec Degradation of insulin degludec is similar to that of human insulin; all metabolites formed are inactive. Liraglutide During the initial 24 hours following administration of a single [ 3 H]-liraglutide dose to healthy subjects, the major component in plasma was intact liraglutide. Liraglutide is endogenously metabolized in a similar manner to large proteins without a specific organ as a major route of elimination.

Specific Populations Geriatric Patients Age had no clinically relevant effect on the pharmacokinetics of XULTOPHY 100/3.6 based on results from a population pharmacokinetic analysis including adult patients up to 83 years treated with XULTOPHY 100/3.6 [see Use in Specific Populations ( 8.5 )] . Male and Female Patients There were no clinically relevant differences in the pharmacokinetics of XULTOPHY 100/3.6 in male and female patients, based on results from a population pharmacokinetic analysis. Racial or Ethnic Groups There were no clinically relevant differences in the pharmacokinetics of XULTOPHY 100/3.6 between the racial and ethnic groups investigated, based on results from a population pharmacokinetic analysis.

Body weight The effect of body weight on the exposure level of the components of XULTOPHY 100/3.6 was investigated in the population pharmacokinetic analysis. Exposure levels decreased with increase in baseline body weight for both insulin degludec and liraglutide. Patients with Renal Impairment XULTOPHY 100/3.6 There is limited experience with XULTOPHY 100/3.6 in patients with mild and moderate renal impairment.

XULTOPHY 100/3.6 has not been studied in patients with severe renal impairment… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 85 words ▾

12.1Mechanism of Action XULTOPHY 100/3.6 XULTOPHY 100/3.6 is a combination product consisting of insulin degludec and liraglutide. Insulin degludec The primary activity of insulin degludec is the regulation of glucose metabolism. Insulin and its analogs lower blood glucose by stimulating peripheral glucose uptake, especially by skeletal muscle and fat, and by inhibiting hepatic glucose production.

Insulin also inhibits lipolysis and proteolysis, and enhances protein synthesis. Liraglutide Liraglutide is a GLP-1 receptor agonist that increases glucose-dependent insulin release, decreases glucagon secretion, and slows gastric emptying.

📦 How Supplied / Storage and Handling ~1 min read ▾

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied XULTOPHY 100/3.6 (insulin degludec and liraglutide) injection is an injection supplied as a clear, colorless solution in a 3 mL prefilled, disposable, single-patient-use pen injector. The XULTOPHY 100/3.6 pen dials in one-unit increments. Dosage Unit/Strength Package size NDC # 3 mL single-patient-use XULTOPHY 100/3.6 pen (100 units/mL insulin degludec and 3.6 mg/mL liraglutide) Package of 5 0169-2911-15 Recommended Storage Dispense in the original sealed carton with the enclosed Instructions for Use.

Prior to first use, XULTOPHY 100/3.6 should be stored between 36°F to 46°F (2°C and 8°C) until the expiration date printed on the label. Store prefilled pens in the carton so they will stay clean and protected from light. Do not store in the freezer or directly adjacent to the refrigerator cooling element.

Do not freeze. Do not use XULTOPHY 100/3.6 if it has been frozen. After first use, the XULTOPHY 100/3.6 pen can be stored for 21 days at controlled room temperature 59°F to 86°F (15°C to 30°C) or in a refrigerator 36°F to 46°F (2°C to 8°C).

Keep all XULTOPHY 100/3.6 pens away from direct heat and light. Always remove the needle after each injection and store the XULTOPHY 100/3.6 pen without a needle attached. This prevents contamination and/or infection, or leakage of the XULTOPHY 100/3.6 pen, and will ensure accurate dosing.

Always use a new needle for each injection to prevent contamination. The storage conditions are summarized in Table 11 : Table 11. Storage Conditions for XULTOPHY 100/3.6 Pen Prior to first use After first use Refrigerated 36°F to 46°F (2°C to 8°C) Room Temperature 59°F to 86°F (15°C to 30°C) Refrigerated 36°F to 46°F (2°C to 8°C) Until expiration date 21 Days

📋 Description ~2 min read ▾

11 DESCRIPTION Insulin degludec Insulin degludec is a long-acting basal human insulin analog. Insulin degludec is produced by a process that includes expression of recombinant DNA in Saccharomyces cerevisiae followed by chemical modification. Insulin degludec differs from human insulin in that the amino acid threonine in position B30 has been omitted and a side-chain consisting of glutamic acid and a C16 fatty acid has been attached (chemical name: LysB29(Nε-hexadecandioyl-γ-Glu) des(B30) human insulin).

Insulin degludec has a molecular formula of C 274 H 411 N 65 O 81 S 6 and a molecular weight of 6.104 kDa. It has the following structure: Figure 1. Structural Formula of Insulin degludec Liraglutide Liraglutide is an analog of human GLP-1 and acts as a GLP-1 receptor agonist.

The peptide precursor of liraglutide, produced by a process that includes expression of recombinant DNA in Saccharomyces cerevisiae , has been engineered to be 97% homologous to native human GLP-1 by substituting arginine for lysine at position 34. Liraglutide is made by attaching a C16 fatty acid (palmitic acid) with a glutamic acid spacer on the remaining lysine residue at position 26 of the peptide precursor. The molecular formula of liraglutide is C 172 H 265 N 43 O 51 and the molecular weight is 3.751 kDa.

It has the following structure: Figure 2. Structural Formula of Liraglutide XULTOPHY 100/3.6 (insulin degludec and liraglutide) injection, for subcutaneous use, is a combination of a long-acting basal human insulin analog, insulin degludec, and a GLP-1 receptor agonist, liraglutide. XULTOPHY 100/3.6 is a sterile, aqueous, clear, and colorless solution.

Each prefilled pen contains 3 mL equivalent to 300 units insulin degludec and 10.8 mg liraglutide. Each mL contains 100 units insulin degludec and 3.6 mg liraglutide. XULTOPHY 100/3.6 contains the following inactive ingredients per mL: glycerol (19.7 mg), phenol (5.7 mg), zinc (55 mcg), and Water for Injection, USP.

XULTOPHY 100/3.6 has a pH of approximately 8.15. Hydrochloric acid or sodium hydroxide may be added to adjust pH. figure_1 figure_2

💬 Information for Patients ~3 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use) Risk of Thyroid C-cell Tumors Inform patients that liraglutide, one of the components of XULTOPHY 100/3.6, causes benign and malignant thyroid C-cell tumors in mice and rats and that the human relevance of this finding is unknown. Counsel patients to report symptoms of thyroid tumors (e.g., a lump in the neck, hoarseness, dysphagia or dyspnea) to their physician [ see Boxed Warning, Warnings and Precautions ( 5.1 )] .

Acute Pancreatitis Inform patients of the potential risk for pancreatitis acute pancreatitis and its symptoms: severe abdominal pain that may radiate to the back, and which may or may not be accompanied by nausea or vomiting. Instruct patients to discontinue XULTOPHY 100/3.6 promptly and contact their physician if pancreatitis is suspected [see Warnings and Precautions ( 5.2 )]. Never Share a XULTOPHY 100/3.6 Pen Between Patients Advise patients that they must never share a XULTOPHY 100/3.6 pen with another person, even if the needle is changed, because doing so carries a risk for transmission of blood-borne pathogens [see Warnings and Precautions ( 5.3 ] .

Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen Inform patients that hypoglycemia is the most common adverse reaction with insulin products. Inform patients of the symptoms of hypoglycemia (e.g., impaired ability to concentrate and react). This may present a risk in situations where these abilities are especially important, such as driving or operating other machinery.

Advise patients who have frequent hypoglycemia or reduced or absent warning signs of hypoglycemia to use caution when driving or operating machinery. Advise patients that changes in insulin regimen can predispose to hyperglycemia or hypoglycemia and that changes in insulin regimen should be made under close medical supervision [see Warnings and Precautions ( 5.4 )]. Overdose due to Medication Errors Inform patients that XULTOPHY 100/3.6 contains two drugs: insulin degludec and liraglutide.

Accidental mix-ups between insulin products have been reported. To avoid medication errors between XULTOPHY 100/3.6 (an insulin containing product) and other insulin products, instruct patients to always check the label before each injection. Advise patients that the administration of more than 50 units of XULTOPHY 100/3.6 daily can result in overdose of the liraglutide component.

Instruct patients not to administer concurrently with other glucagon-like peptide-1 receptor agonists [see Warnings and Precautions (5.5 )] . Acute Kidney Injury Due to Volume Depletion Inform patients of the potential risk of acute kidney injury due to dehydration associated with gastrointestinal adverse reactions. Advise patients to take precautions to avoid fluid depletion.

Inform patients of the signs and symptoms of acute kidney injury and instruct them to promptly report any of these signs or symptoms or persistent (or extended) nausea, vomiting, and diarrhea to their healthcare provider [see Warnings and Precautions ( 5.7 )]. Severe Gastrointestinal Adverse Reactions Inform patients of the potential risk of severe gastrointestinal adverse reactions. Instruct patients to contact their healthcare provider if they have severe or persistent gastrointestinal symptoms [see Warnings and Precautions ( 5.8 )].

Hypersensitivity Reactions Inform patients that serious hypersensitivity reactions have been reported during postmarketing use of liraglutide, one of the components of XULTOPHY 100/3.6. Advise patients on the symptoms of hypersensitivity reactions and instruct them must stop taking XULTOPHY 100/3.6 and seek medical advice promptly [see Warnings and Precautions ( 5.9 )] . Acute Gallbladder Disease Inform patients of the potential risk for cholelithiasis or cholecystitis.

Instruct patients to contact their physician if cholelithiasis or cholecystitis is suspected for appropriate cl… [Excerpted — this section continues on DailyMed.]

💬 Medication Guide ~3 min read ▾

Medication Guide XULTOPHY ® 100/3.6 (ZUL-to-fye) (insulin degludec and liraglutide) Injection, for subcutaneous injection Read this Medication Guide before you start using XULTOPHY 100/3.6 and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.

What is the most important information I should know about XULTOPHY 100/3.6? XULTOPHY 100/3.6 may cause serious side effects, including: • Possible thyroid tumors, including cancer. Tell your healthcare provider if you get a lump or swelling in your neck, hoarseness, trouble swallowing, or shortness of breath.

These may be symptoms of thyroid cancer. In studies with rats and mice, liraglutide, one of the components of XULTOPHY 100/3.6, and medicines that work like liraglutide caused thyroid tumors, including thyroid cancer. It is not known if XULTOPHY 100/3.6 will cause thyroid tumors or a type of thyroid cancer called medullary thyroid carcinoma (MTC) in people. • Do not use XULTOPHY 100/3.6 if you or any of your family have ever had a type of thyroid cancer called medullary thyroid carcinoma (MTC), or if you have an endocrine system condition called Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).

What is XULTOPHY 100/3.6? • XULTOPHY 100/3.6 is an injectable prescription medicine that contains 2 diabetes medicines, insulin degludec, 100 units/mL, and liraglutide, 3.6 mg/mL. XULTOPHY 100/3.6 should be used along with diet and exercise to lower blood sugar (glucose) in adults with type 2 diabetes mellitus. • XULTOPHY 100/3.6 is not recommended as the first choice of medicine for treating diabetes. • XULTOPHY 100/3.6 is not recommended for use in combination with any other product containing liraglutide or another glucagon-like peptide 1 receptor agonist (GLP-1 receptor agonist). • XULTOPHY 100/3.6 is not for use in people with type 1 diabetes or people with diabetic ketoacidosis (increased ketones in the blood or urine). • It is not known if XULTOPHY 100/3.6 can be used with mealtime insulin. • It is not known if XULTOPHY 100/3.6 is safe and effective for use in children.

Who should not use XULTOPHY 100/3.6? Do not use XULTOPHY 100/3.6 if: • you or any of your family have ever had a type of thyroid cancer called medullary thyroid carcinoma (MTC) or if you have an endocrine system condition called Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). • you are allergic to insulin degludec, liraglutide or any of the ingredients in XULTOPHY 100/3.6. See the end of this Medication Guide for a complete list of ingredients in XULTOPHY 100/3.6. • you are having an episode of low blood sugar (hypoglycemia).

What should I tell my healthcare provider before using XULTOPHY 100/3.6? Before using XULTOPHY 100/3.6, tell your healthcare provider about all your medical conditions, including if you: • have or have had problems with your pancreas, kidneys, or liver. • have heart failure or other heart problems. If you have heart failure, it may get worse while you take TZDs with XULTOPHY 100/3.6. • have severe problems with your stomach, such as slowed emptying of your stomach (gastroparesis) or problems with digesting food. • are taking certain medicines called GLP-1 receptor agonists. • have had an allergic reaction to a GLP-1 receptor agonist medicine. • are scheduled to have surgery or other procedures that use anesthesia or deep sleepiness (deep sedation). • are pregnant or plan to become pregnant.

It is not known if XULTOPHY 100/3.6 will harm your unborn baby. Tell your healthcare provider if you become pregnant or think you may be pregnant while using XULTOPHY 100/3.6. • are breastfeeding or plan to breastfeed. It is not known if XULTOPHY 100/3.6 passes into your breast milk.

Talk to your healthcare provider about the best way to feed your baby while using XULTOPHY 100/3.6. Tell your healthcare provider about all the medicines you take, including prescription a… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacokinetics ~3 min read ▾

12.3Pharmacokinetics Overall, the pharmacokinetics of insulin degludec and liraglutide were not affected in a clinically relevant manner when administered as XULTOPHY 100/3.6. Absorption In patients with type 2 diabetes mellitus (mean body weight 87.5 kg) reaching the maximum daily dose (50 units/1.8 mg) of XULTOPHY 100/3.6, the estimated mean steady-state exposure (AUC 0-24 h) of insulin degludec was 113 h*nmol/L and of liraglutide 1227 h*ng/mL based on population pharmacokinetic analysis. The corresponding maximum concentrations were 5196 pmol/L for insulin degludec and 55 ng/mL for liraglutide.

Steady state concentrations of insulin degludec and liraglutide are reached after 2-3 days of daily administration. Distribution Insulin degludec and liraglutide are extensively bound to plasma proteins >99% and >98%, respectively. Elimination The half-life of insulin degludec is approximately 25 hours and the half-life of liraglutide is approximately 13 hours.

Metabolism Insulin degludec Degradation of insulin degludec is similar to that of human insulin; all metabolites formed are inactive. Liraglutide During the initial 24 hours following administration of a single [ 3 H]-liraglutide dose to healthy subjects, the major component in plasma was intact liraglutide. Liraglutide is endogenously metabolized in a similar manner to large proteins without a specific organ as a major route of elimination.

Specific Populations Geriatric Patients Age had no clinically relevant effect on the pharmacokinetics of XULTOPHY 100/3.6 based on results from a population pharmacokinetic analysis including adult patients up to 83 years treated with XULTOPHY 100/3.6 [see Use in Specific Populations ( 8.5 )] . Male and Female Patients There were no clinically relevant differences in the pharmacokinetics of XULTOPHY 100/3.6 in male and female patients, based on results from a population pharmacokinetic analysis. Racial or Ethnic Groups There were no clinically relevant differences in the pharmacokinetics of XULTOPHY 100/3.6 between the racial and ethnic groups investigated, based on results from a population pharmacokinetic analysis.

Body weight The effect of body weight on the exposure level of the components of XULTOPHY 100/3.6 was investigated in the population pharmacokinetic analysis. Exposure levels decreased with increase in baseline body weight for both insulin degludec and liraglutide. Patients with Renal Impairment XULTOPHY 100/3.6 There is limited experience with XULTOPHY 100/3.6 in patients with mild and moderate renal impairment.

XULTOPHY 100/3.6 has not been studied in patients with severe renal impairment [see Warnings and Precautions ( 5.7 )]. Insulin degludec Insulin degludec has been studied in a pharmacokinetic study in 32 subjects (n=6/group) with normal or impaired renal function/end-stage renal disease following administration of a single dose (0.4 U/kg) of insulin degludec. Renal function was defined using creatinine clearance (Clcr) as follows: >80 mL/min (normal), 50-80 mL/min (mild), 30-50 mL/min (moderate) and <30 mL/min (severe).

Subjects requiring dialysis were classified as having end-stage renal disease (ESRD). Total exposure (AUC IDeg,0-120h,SD ) of insulin degludec was similar in subjects with normal and impaired renal function. No clinically relevant difference in the pharmacokinetics of insulin degludec was identified between healthy subjects and subjects with renal impairment.

Hemodialysis did not affect clearance of insulin degludec (CL/F IDeg,SD ) in subjects with ESRD [see Warnings and Precautions ( 5.7 )] . Liraglutide The single-dose pharmacokinetics of liraglutide were evaluated in subjects with varying degrees of renal impairment. Subjects with mild (estimated creatinine clearance 50-80 mL/min) to severe (estimated creatinine clearance <30 mL/min) renal impairment and subjects with end-stage renal disease requiring dialysis were included in the trial.

Compared to healthy subjects, liraglutide AUC in mild, moderat… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacodynamics 95 words ▾

12.2Pharmacodynamics Following a single-dose administration, XULTOPHY 100/3.6 has a duration of action reflecting the combination of the individual glucodynamic action profiles of insulin degludec and liraglutide. Following once-daily administration, XULTOPHY 100/3.6 lowers fasting plasma glucose levels and postprandial glucose levels. Cardiac Electrophysiology (QTc): XULTOPHY 100/3.6 The effect of XULTOPHY 100/3.6 on QTc has not been studied.

Liraglutide The effect of liraglutide, one of the components of XULTOPHY 100/3.6, on cardiac repolarization was tested in a QTc study. Liraglutide, at steady state concentrations with daily doses up to 1.8 mg, did not produce QTc prolongation.

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES

14.1Overview of Clinical Studies A total of 3908 patients with type 2 diabetes mellitus participated in 6 randomized, parallel and active or placebo-controlled phase 3 trials of 26 weeks duration. Three studies were conducted in patients inadequately controlled on one or more OADs (e.g. metformin, pioglitazone, sulfonylurea, or sodium-glucose cotransporter-2 inhibitors (SGLT2i) ( Tables 5-7 ). Three studies were conducted in patients converting from liraglutide or basal insulin: one study was conducted in patients converting from liraglutide (with doses up to 1.8 mg), ( Table 8 ), one study was conducted in patients converting from any basal insulin ( Table 9 ), and one study was conducted in patients converting from insulin glargine U-100 ( Table 10 ).

In all trials, XULTOPHY 100/3.6 was titrated twice weekly by increments or decrements of 2 units (2 units insulin degludec/0.072 mg liraglutide), towards a pre-specified fasting blood glucose target. The same titration algorithm was applied for basal insulin comparators.

14.2Patients with Type 2 Diabetes Mellitus Uncontrolled on OAD Treatment NCT01336023: The efficacy and safety of XULTOPHY 100/3.6 compared to insulin degludec and liraglutide, all administered once-daily, was studied in a 26-week randomized, open-label, three-arm parallel trial in 1,660 patients with type 2 diabetes mellitus inadequately controlled on 1-2 OADs (metformin or metformin with or without pioglitazone). The mean age of the trial population was 55 years and mean duration of diabetes was 7 years. 51% were male.

62% were White, 7% were Black or African American and 15% were Hispanic or Latino ethnicity, 5% of patients had eGFR <60 mL/min/1.73 m 2 ; no patients had eGFR <30 mL/min/1.73 m 2 . The mean BMI was 31.2 kg/m 2 . The starting dose of XULTOPHY 100/3.6 was 10 units (10 units insulin degludec/0.36 mg liraglutide).

The starting dose of insulin degludec was 10 units. XULTOPHY 100/3.6 and insulin degludec were titrated twice weekly towards a target fasting blood glucose goal of 72 to 90 mg/dL. Patients in the liraglutide arm followed a fixed dose escalation scheme with a starting dose of 0.6 mg and a dose increase of 0.6 mg weekly until a daily dose of 1.8 mg was reached.

Patients continued on pre-trial treatment with metformin or metformin and pioglitazone throughout the trial. At the end of 26 weeks, treatment with XULTOPHY 100/3.6, insulin degludec, and liraglutide resulted in a reduction in HbA 1c from baseline of 1.81%, 1.35% and 1.21%, respectively, (see Table 5 ). The end of trial dose of XULTOPHY 100/3.6 was 38 units (38 units insulin degludec/1.37 mg liraglutide).

Table 5. Results of a 26-Week Trial with XULTOPHY 100/3.6 in Patients with Type 2 Diabetes Mellitus Inadequately Controlled on Metformin Alone or in Combination with Pioglitazone XULTOPHY 100/3.6 + metformin ± pioglitazone Insulin degludec + metformin ± pioglitazone Liraglutide + metformin ± pioglitazone Total (N) 833 413 414 HbA 1c (%) Baseline 8.3 8.3

8.3End of Trial (LS Mean) # 6.5 6.9

7.1Change from baseline (LS Mean) # -1.81 -1.35 -1.21 Estimated treatment difference [95% CI] # -- -0.46% [-0.59; -0.34] A -0.6% [-0.72; -0.47] A Percentage of patients achieving HbA 1c <7% ## 74.1% 60.5% 56% Fasting Plasma Glucose (FPG) (mg/dL) Baseline 166 169 163 End of Trial (LS Mean) # 104 107 133 Change from baseline (LS Mean) # -61.8 -59.2 -32.4 A p<0.01. Primary endpoint was tested for non-inferiority of XULTOPHY 100/3.6 to insulin degludec based on pre-specified non-inferiority margin of 0.3% and for superiority of XULTOPHY 100/3.6 to liraglutide. # Estimated using an ANCOVA with treatment, baseline HbA 1c stratum, sub-study, concomitant diabetes treatment and country as factors and baseline response as covariate.

Multiple imputation modeled “return to baseline” of the treatment effect for subjects having missing week 26 data. ## Patients with missing HbA 1c value at week 26 data were considered non-responders. Ther… [Excerpted — this section continues on DailyMed.]

🧪 Nonclinical Toxicology ~3 min read ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility XULTOPHY 100/3.6 No studies have been conducted with the XULTOPHY 100/3.6 combination to evaluate carcinogenesis, mutagenesis or impairment of fertility. The following data are based upon studies with insulin degludec and liraglutide individually. Insulin degludec Standard 2-year carcinogenicity studies in animals have not been performed to evaluate the carcinogenic potential of insulin degludec.

In a 52-week study including human insulin (NPH insulin) as comparator, Sprague-Dawley rats were dosed subcutaneously with insulin degludec at 3.3, 6.7, and 10 U/kg/day, resulting in 5 times the human exposure (AUC) when compared to a human subcutaneous dose of

0.75U/kg/day. Human insulin was dosed at

6.7U/kg/day. No treatment-related increases in incidences of hyperplasia, benign or malignant tumors were recorded in female mammary glands from rats dosed with insulin degludec and no treatment related changes in the female mammary gland cell proliferation were found using BrdU incorporation. Further, no treatment related changes in the occurrence of hyperplastic or neoplastic lesions were seen in any animals dosed with insulin degludec when compared to vehicle or human insulin.

Genotoxicity testing of insulin degludec was not performed. In a combined fertility and embryo-fetal study in male and female rats, treatment with insulin degludec up to 21 U/kg/day (approximately 5 times the human subcutaneous dose of

0.75U/kg/day, based on U/body surface area) prior to mating and in female rats during gestation had no effect on mating performance and fertility. Liraglutide A 104-week carcinogenicity study was conducted in male and female CD-1 mice at doses of 0.03, 0.2, 1.0, and 3.0 mg/kg/day liraglutide administered by bolus subcutaneous injection yielding systemic exposures 0.2-, 2-, 10- and 45-times the human exposure, respectively, at the MRHD of 1.8 mg/day based on plasma AUC comparison. A dose-related increase in benign thyroid C-cell adenomas was seen in the 1.0 and the 3.0 mg/kg/day groups with incidences of 13% and 19% in males and 6% and 20% in females, respectively.

C-cell adenomas did not occur in control groups or 0.03 and 0.2 mg/kg/day groups. Treatment-related malignant C-cell carcinomas occurred in 3% of females in the 3.0 mg/kg/day group. Thyroid C-cell tumors are rare findings during carcinogenicity testing in mice.

A treatment-related increase in fibrosarcomas was seen on the dorsal skin and subcutis, the body surface used for drug injection, in males in the 3 mg/kg/day group. These fibrosarcomas were attributed to the high local concentration of drug near the injection site. The liraglutide concentration in the clinical formulation (6 mg/mL) is 10-times higher than the concentration in the formulation used to administer 3 mg/kg/day liraglutide to mice in the carcinogenicity study (0.6 mg/mL).

A 104-week carcinogenicity study was conducted in male and female Sprague Dawley rats at doses of 0.075, 0.25 and 0.75 mg/kg/day liraglutide administered by bolus subcutaneous injection with exposures 0.5-, 2- and 8-times the human exposure, respectively, resulting from the MRHD based on plasma AUC comparison. A treatment-related increase in benign thyroid C-cell adenomas was seen in males in 0.25 and 0.75 mg/kg/day liraglutide groups with incidences of 12%, 16%, 42%, and 46% and in all female liraglutide-treated groups with incidences of 10%, 27%, 33%, and 56% in 0 (control), 0.075, 0.25, and 0.75 mg/kg/day groups, respectively.

A treatment-related increase in malignant thyroid C-cell carcinomas was observed in all male liraglutide-treated groups with incidences of 2%, 8%, 6%, and 14% and in females at 0.25 and 0.75 mg/kg/day with incidences of 0%, 0%, 4%, and 6% in 0 (control), 0.075, 0.25, and 0.75 mg/kg/day groups, respectively. Thyroid C-cell carcinomas are rare findings during carcinogenicity testing in rats. Studies in mice demonstrated that l… [Excerpted — this section continues on DailyMed.]

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ~3 min read ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility XULTOPHY 100/3.6 No studies have been conducted with the XULTOPHY 100/3.6 combination to evaluate carcinogenesis, mutagenesis or impairment of fertility. The following data are based upon studies with insulin degludec and liraglutide individually. Insulin degludec Standard 2-year carcinogenicity studies in animals have not been performed to evaluate the carcinogenic potential of insulin degludec.

In a 52-week study including human insulin (NPH insulin) as comparator, Sprague-Dawley rats were dosed subcutaneously with insulin degludec at 3.3, 6.7, and 10 U/kg/day, resulting in 5 times the human exposure (AUC) when compared to a human subcutaneous dose of

0.75U/kg/day. Human insulin was dosed at

6.7U/kg/day. No treatment-related increases in incidences of hyperplasia, benign or malignant tumors were recorded in female mammary glands from rats dosed with insulin degludec and no treatment related changes in the female mammary gland cell proliferation were found using BrdU incorporation. Further, no treatment related changes in the occurrence of hyperplastic or neoplastic lesions were seen in any animals dosed with insulin degludec when compared to vehicle or human insulin.

Genotoxicity testing of insulin degludec was not performed. In a combined fertility and embryo-fetal study in male and female rats, treatment with insulin degludec up to 21 U/kg/day (approximately 5 times the human subcutaneous dose of

0.75U/kg/day, based on U/body surface area) prior to mating and in female rats during gestation had no effect on mating performance and fertility. Liraglutide A 104-week carcinogenicity study was conducted in male and female CD-1 mice at doses of 0.03, 0.2, 1.0, and 3.0 mg/kg/day liraglutide administered by bolus subcutaneous injection yielding systemic exposures 0.2-, 2-, 10- and 45-times the human exposure, respectively, at the MRHD of 1.8 mg/day based on plasma AUC comparison. A dose-related increase in benign thyroid C-cell adenomas was seen in the 1.0 and the 3.0 mg/kg/day groups with incidences of 13% and 19% in males and 6% and 20% in females, respectively.

C-cell adenomas did not occur in control groups or 0.03 and 0.2 mg/kg/day groups. Treatment-related malignant C-cell carcinomas occurred in 3% of females in the 3.0 mg/kg/day group. Thyroid C-cell tumors are rare findings during carcinogenicity testing in mice.

A treatment-related increase in fibrosarcomas was seen on the dorsal skin and subcutis, the body surface used for drug injection, in males in the 3 mg/kg/day group. These fibrosarcomas were attributed to the high local concentration of drug near the injection site. The liraglutide concentration in the clinical formulation (6 mg/mL) is 10-times higher than the concentration in the formulation used to administer 3 mg/kg/day liraglutide to mice in the carcinogenicity study (0.6 mg/mL).

A 104-week carcinogenicity study was conducted in male and female Sprague Dawley rats at doses of 0.075, 0.25 and 0.75 mg/kg/day liraglutide administered by bolus subcutaneous injection with exposures 0.5-, 2- and 8-times the human exposure, respectively, resulting from the MRHD based on plasma AUC comparison. A treatment-related increase in benign thyroid C-cell adenomas was seen in males in 0.25 and 0.75 mg/kg/day liraglutide groups with incidences of 12%, 16%, 42%, and 46% and in all female liraglutide-treated groups with incidences of 10%, 27%, 33%, and 56% in 0 (control), 0.075, 0.25, and 0.75 mg/kg/day groups, respectively.

A treatment-related increase in malignant thyroid C-cell carcinomas was observed in all male liraglutide-treated groups with incidences of 2%, 8%, 6%, and 14% and in females at 0.25 and 0.75 mg/kg/day with incidences of 0%, 0%, 4%, and 6% in 0 (control), 0.075, 0.25, and 0.75 mg/kg/day groups, respectively. Thyroid C-cell carcinomas are rare findings during carcinogenicity testing in rats. Studies in mice demonstrated that liraglutide-induced C-cell… [Excerpted — this section continues on DailyMed.]

📄 Recent Major Changes 25 words ▾

Warnings and Precautions, Severe Gastrointestinal Adverse Reactions ( 5.8 ) …………. 10/2025 Pulmonary Aspiration During General Anesthesia or Deep Sedation ( 5.13 ) ……………..…………………….…… 11/2024

📄 Package Label / Principal Display Panel 100 words ▾

PACKAGE/LABEL PRINCIPAL DISPLAY PANEL Xultophy ® 100/3.6 NDC 0169-2911-15 List: 291115 (insulin degludec and liraglutide) injection For Single Patient Use Only 100 units/mL and 3.6 mg/mL With each unit of insulin degludec, the pen also delivers 0.036 mg of liraglutide 5x3 mL Prefilled Pens For subcutaneous use only Recommended for use with NovoFine ® , Novofine ® Plus or NovoTwist ® disposable needles. Must be refrigerated until first use. Store at 36°F – 46°F (2°C – 8°C).

Do not freeze. Protect from light. Rx Only Dispense in this sealed carton.

ATTENTION: Dispense the enclosed Medication Guide to each patient. carton_5ct

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗

Medicaid utilization & spend

📍 This exact package only: Medicaid data is reported per full 11-digit NDC — labeler, product and pack size — so every number here is for this package alone, not the drug overall. Other pack sizes report separately.
💊 Pharmacy benefit only: These are Medicaid outpatient pharmacy claims, billed by NDC. They exclude the medical benefit — clinic- or hospital-administered drugs billed under HCPCS J-codes — so drugs used mostly that way (e.g. Avastin, Lucentis, Keytruda) can look low or missing here. That’s expected, not an error.
📅 Q1 2025 – Q1 2026 · 5 quarters of data
ⓘ The newest quarter is usually incomplete when first published; states restate recent quarters in later CMS releases, so the latest figures typically revise upward. State coverage-policy changes can also shift quarter-to-quarter totals.
Prescriptions last 4 qtrs
568
Units reimbursed last 4 qtrs
8.9K
Gross reimbursed last 4 qtrs
$768.7K
Avg / prescription
$1,353.34
Avg / unit
$86.3028
Latest quarter Q1 2026
108Rx
Medicaid pays / mL
$86.3028
gross reimbursed
vs
NADAC / mL
$85.8856
acquisition cost
=
Spread
+$0.4172
+0% vs cost
What Medicaid paid per mL (before rebates; includes the pharmacy’s dispensing fee) compared with NADAC — the average price pharmacies pay to buy the drug. A positive spread means Medicaid reimbursed more than the purchase price, before manufacturer rebates.
Fee-for-service vs managed care ⓘ
59% FFS 41% MCO
Fee-for-service · 337 Rx Managed care · 231 Rx
State Medicaid map
Alaska: 135 units · 18.4 per 100k residents AK Maine: no data reported ME Washington: no data reported WA Idaho: no data reported ID Montana: no data reported MT North Dakota: no data reported ND Minnesota: no data reported MN Wisconsin: no data reported WI Michigan: no data reported MI New York: 1,764 units · 9.0 per 100k residents NY Vermont: no data reported VT New Hampshire: no data reported NH Oregon: no data reported OR Nevada: no data reported NV Wyoming: no data reported WY South Dakota: no data reported SD Iowa: no data reported IA Illinois: no data reported IL Indiana: no data reported IN Ohio: 129 units · 1.1 per 100k residents OH Pennsylvania: 1,155 units · 8.9 per 100k residents PA New Jersey: no data reported NJ Massachusetts: no data reported MA California: 3,051 units · 7.8 per 100k residents CA Utah: no data reported UT Colorado: no data reported CO Nebraska: no data reported NE Missouri: no data reported MO Kentucky: 1,065 units · 23.5 per 100k residents KY West Virginia: no data reported WV Virginia: no data reported VA Maryland: no data reported MD Connecticut: 516 units · 14.3 per 100k residents CT Rhode Island: no data reported RI Arizona: no data reported AZ New Mexico: no data reported NM Kansas: no data reported KS Arkansas: no data reported AR Tennessee: no data reported TN North Carolina: 1,092 units · 10.1 per 100k residents NC South Carolina: no data reported SC Delaware: no data reported DE Oklahoma: no data reported OK Louisiana: no data reported LA Mississippi: no data reported MS Alabama: no data reported AL Georgia: no data reported GA D.C.: no data reported DC Hawaii: no data reported HI Texas: no data reported TX Florida: no data reported FL
Units reimbursed · per 100k residents
1.123.5
gray = no data reported ⓘ
Colors are per 100,000 residents, so big states don’t automatically dominate. Tap or hover a state for its actual totals.
Tap or hover a state
…for its Medicaid breakdown
🏆 Top states by units · per 100k residents
1 Kentucky 23.5 /100k
2 Alaska 18.4 /100k
3 Connecticut 14.3 /100k
4 North Carolina 10.1 /100k
5 New York 9.0 /100k
6 Pennsylvania 8.9 /100k
7 California 7.8 /100k
8 Ohio 1.1 /100k
National units — by quarter
💵 About the dollar figures: “reimbursed” is what Medicaid paid pharmacies before confidential manufacturer rebates, so the program’s real net cost is lower than these numbers. Fee-for-service and managed-care claims are combined unless split above. Source: CMS State Drug Utilization Data; per-100k rates use 2023 Census population estimates.

Medicare Part D spend CMS · PART D · 2026 (Q1)

Medicare Part D (outpatient prescription) spending for Xultophy 100-3.6 — the program that covers self-administered drugs. 1 manufacturer.
⚠️ Drug-level data: CMS publishes Part D spending by drug, not by NDC — these figures combine every manufacturer, strength and package size sold under the name Xultophy 100-3.6. That’s a different level of aggregation than the Medicaid card above, which is specific to this exact 11-digit NDC (pack size included), so the two aren’t directly comparable.
Period
Total Part D spend
$10.86M
Claims incl. refills
6.7K
Beneficiaries
4.8K
Spend / beneficiary
$2,255.04
Spend / claim
$1,622.05
Trend by period
💵 About the dollar figures: spending is what Part D plans paid before confidential manufacturer rebates, so the program’s real net cost is lower. A blank patient count means fewer than 11 people — CMS hides counts that small to protect privacy. Source: CMS Medicare Quarterly Part D Spending by Drug (data.cms.gov), updated quarterly.
← 00169-2800-15 · Novo 00169-3003-15 · Novo →
For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.