Drug Interaction Report

Pioglitazone and Insulin Degludec (Rdna Origin) Injection: Interaction Details

A pharmacist-reviewed analysis of the Pioglitazone and Insulin Degludec (Rdna Origin) Injection interaction: the documented clinical effects, severity rating, onset, mechanism, and management considerations, with cited references throughout.

AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature

Insulin Degludec (Rdna Origin) Injection

Ryzodeg® (as a combination product containing Insulin Degludec and Insulin Aspart) Tresiba Tresiba® Xultophy® (as a combination product containing Insulin Degludec and Liraglutide)
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Pioglitazone

Actos Actos® Oseni® (as a combination product containing Alogliptin, Pioglitazone)
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Dr. Brian Staiger, PharmD, BCPS
Updated Aug 8, 2026
Editorial policy · Data sources
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Interaction severity
Major
Potentially serious — often needs a change or close monitoring.
How we grade severity & evidence

Severity levels

  • Contraindicated: These should generally not be used together.
  • Major: Potentially serious — often needs a change or close monitoring.
  • Moderate: Can be significant — usually manageable with monitoring.
  • Minor: Usually limited clinical impact.

Evidence grades

  • Established: Well documented — supported by controlled studies or strong clinical data.
  • Probable: Good supporting evidence, though not definitively proven.
  • Suspected: Some evidence suggests this interaction, but it is not well established.
  • Possible: Limited or conflicting evidence; the interaction may occur.
  • Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.

Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.

Of 60 documented Pioglitazone interactions, 29 are rated major — including this one.
Worried about symptoms right now? Contact your pharmacist or prescriber, or call Poison Control at 1-800-222-1222 (US). Call 911 for an emergency.
Onset
unspecified
Evidence
theoretical
Severity
Major

What happens

Increased risk of fluid retention and heart failure; increased risk of hypoglycemia

Interaction Deep Dive

Use caution with coadministration of insulin and peroxisome proliferator-activated receptor (PPAR)-gamma agonists, as dose-related fluid retention can develop that may precede or worsen heart failure. Monitor for signs and symptoms of heart failure if coadministration is indicated. Consider dosage reduction or discontinuation of the PPAR-gamma agonist if heart failure develops1. Concomitant use of insulin and a PPAR-gamma agonist may also cause hypoglycemia. If hypoglycemia occurs, decrease the insulin dosage by 10% to 25% and adjust based on individual glycemic response 23.

Why it happens (mechanism)

Unknown

Common questions

Can I take Pioglitazone and Insulin Degludec (Rdna Origin) Injection together?

Increased risk of fluid retention and heart failure; increased risk of hypoglycemia Always confirm with your pharmacist or prescriber before making any change.

How serious is the Pioglitazone and Insulin Degludec (Rdna Origin) Injection interaction?

It is rated major. Potentially serious — often needs a change or close monitoring.

How quickly could this interaction happen?

The documented onset is "unspecified". The timing of this interaction is not well characterized.

How strong is the evidence for this interaction?

The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.

Questions for your pharmacist

  • Does my dose of Pioglitazone or Insulin Degludec (Rdna Origin) Injection need adjusting while I take them together?
  • What symptoms should prompt me to call you or my prescriber right away?
  • Does the timing of my doses matter for this combination?
  • Is there a safer alternative to one of these medications for me?

References (3)

  1. Product Information: APIDRA(R) subcutaneous injection solution, intravenous injection solution, insulin glulisine rDNA origin subcutaneous injection solution, intravenous injection solution. Sanofi-Aventis U.S. LLC (per FDA), Bridgewater, NJ, 2014. DailyMed
  2. Product Information: ACTOPLUS MET oral tablets, pioglitazone metformin HCl oral tablets. Takeda Pharmaceuticals America Inc. (per manufacturer), Deerfield, IL, 2016. DailyMed
  3. Product Information: ACTOPLUS MET XR oral extended-release tablets, pioglitazone metformin HCl oral extended-release tablets. Takeda Pharmaceuticals America, Inc. (per Manufacturer), Deerfield, IL, 2016.
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Beyond drug–drug

These medications also interact with supplements

Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:

Pioglitazone + Activated Charcoal Beer Grapefruit Siberian Cocklebur St. John's Wort Wine Acacia Rigidula Acai + 348 more

major · moderate · minor — check everything you take with our drug–supplement interaction checker.

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This information is for education, not a substitute for professional medical advice. Do not start, stop, or change any medication without talking to your pharmacist or prescriber.