Comparing Mounjaro And Trulicity Side Effects

In our latest question and answer, the pharmacist compares the gastrointesterinal side effects of Mounjaro and Trulicity.

Question

Hello, could you please provide insight into the comparative side effects of Trulicity and Mounjaro? My husband currently uses Trulicity, and the dosage was recently increased due to a rise in his A1C levels. However, he's experiencing significant stomach discomfort and frequent nighttime diarrhea as a result. I came across discussions on a forum and another website where individuals mentioned experiencing fewer side effects with Mounjaro. Are there any potential drawbacks or concerns associated with switching to Mounjaro from Trulicity? Additionally, do both medications offer similar benefits for managing type 2 diabetes? Any guidance you can offer would be greatly appreciated. Thank you, Laura.

Asked by Laura On Aug 30, 2023

Answered by
Medical Content Reviewed By HelloPharmacist Staff

Published Aug 31, 2023
Last updated Feb 23, 2024

Key points

  • Trulicity and Mounjaro are both GLP-1 receptor agonists with similar mechanisms of action for lowering blood sugar levels and inducing weight loss.
  • While they share similar gastrointestinal side effects, Mounjaro seems to cause slightly more severe GI side effects, leading to a higher discontinuation rate in clinical trials compared to Trulicity.

Quick Answer

Hello and thank you for reaching out! Both Trulicity and Mounjaro belong to the same class of medications known as GLP-1 receptor agonists (also known as GLP-1 RAs). They share similar side effects, but according to the prescribing information for each, which reports side effects experienced in clinical trials, there are some slight differences. Individuals taking Mounjaro appear to experience slightly more severe gastrointestinal side effects than those taking Trulicity.

Additionally, studies show that, on average, Mounjaro reduces blood glucose, A1c and body weight to a greater extent than Trulicity does, but whether or not this directs relates to better health outcomes is uncertain.

Detailed Answer

Despite being categorized within the same drug class, Trulicity and Mounjaro have slightly different mechanisms of action.

Trulicity works as a GLP-1 (glucagon-like peptide-1) agonist. This hormone helps to lower blood sugar levels in two ways:

  • By triggering the pancreas to produce insulin, a hormone that helps cells absorb sugar from the bloodstream; and by slowing gastric emptying which delays the entry of sugar into the bloodstream.
  • The medication also decreases the amount of glucose produced by the liver and makes a person feel more satiated and fuller, potentially leading to weight loss.

Mounjaro, similar to Trulicity, is also a GLP-1 agonist but it has an additional mechanism of action: acting as an agonist for GIP.

GIP, glucose-dependent insulinotropic polypeptide, is a hormone in your body that has two main roles in controlling blood sugar levels.

First, it helps prevent the release of a hormone called glucagon. Glucagon's role is to increase blood sugar when it's too low, so by inhibiting it, GIP helps keep blood sugar from getting too high. Second, GIP stimulates the release of insulin, a hormone that lowers blood sugar.

Regarding adverse reactions, both Trulicity and Mounjaro have similar side effects occurring at roughly the same rate. Gastrointestinal side effects are the most common with GLP-1 drugs, and they are also the primary reason people discontinue the medication. These side effects include:

  • Nausea
  • Diarrhea
  • Flatulence
  • Abdominal distension
  • Constipation
  • Dyspepsia
  • Vomiting

It would be challenging to predict which drug would be better tolerated by any individual, as the side effect profiles are so similar.

Furthermore, the side effects from these drugs are mostly dose-dependent, meaning the higher the dose, the greater the chance of side effects occurring. Therefore, comparing the two at different dosages can be challenging.

Comparing Gastrointestinal (GI) Side Effects

When comparing the prescribing information for Trulicity and Mounjaro, on average, while the frequency of gastrointestinal side effects for each is essentially the same, individuals discontinued Mounjaro due to GI side effects at a higher rate than Trulicity in clinical trials.

Below are excerpts from the prescribing information for each drug:

Trulicity

Gastrointestinal Adverse Reactions
In the pool of placebo-controlled trials, gastrointestinal (GI) adverse reactions occurred more frequently among patients who received Trulicity compared to patients who received placebo (placebo 21%, 0.75 mg 32%, 1.5 mg 41%). A higher percentage of patients who received Trulicity 0.75 mg (1.3%) and Trulicity 1.5 mg (3.5%) discontinued treatment due to GI adverse reactions than patients who received placebo (0.2%). Investigators graded the severity of GI adverse reactions that occurred in those treated with 0.75 mg and 1.5 mg of Trulicity as "mild" in 58% and 48% of cases, respectively, "moderate" in 35% and 42% of cases, respectively, or "severe" in 7% and 11% of cases, respectively.

Trulicity Prescribing Information

Mounjaro

Gastrointestinal Adverse Reactions In the pool of placebo-controlled trials, gastrointestinal adverse reactions occurred more frequently among patients receiving Mounjaro than placebo (placebo 20.4%, Mounjaro 5 mg 37.1%, Mounjaro 10 mg 39.6%, Mounjaro 15 mg 43.6%). More patients receiving Mounjaro 5 mg (3.0%), Mounjaro 10 mg (5.4%), and Mounjaro 15 mg (6.6%) discontinued treatment due to gastrointestinal adverse reactions than patients receiving placebo (0.4%). The majority of reports of nausea, vomiting, and/or diarrhea occurred during dose escalation and decreased over time.
Mounjaro Prescribing Information

I highlighted two crucial parts in the excerpts above, so let's focus on those:

  • Trulicity and Mounjaro both cause gastrointestinal side effects at a similar rate. At the highest dose of each, 41% of individuals experience some sort of GI side effect on Trulicity. With Mounjaro, 43% experience some type of GI side effect.

  • The data suggests gastrointestinal side effects are generally more severe with Mounjaro. During clinical trials, 6.6% of individuals taking the highest dose of the drug (15mg) stopped taking it because of the gastrointestinal side effects. Compare this to only 3.5% of individuals taking the highest dose of Trulicity (although it's important to note here that the prescribing information only lists discontinuation rates at a dose of 1.5mg and doses up to 4.5mg can be used).

Other Side Effects

Gastrointestinal side effects are typically the most concerning for individuals when it comes to the known adverse reactions for both Mounjaro and Trulicity.

Other side effects are generally less frequent and have less severe impacts than GI issues, and don’t vary much between the various GLP-1 drugs available.

  • Hypoglycemia (low blood sugar), while significant, is somewhat uncommon with GLP-1 RA drugs unless they are being used in combination with other drugs used for diabetes.
  • GLP-1 receptor agonists can sometimes cause minor injection-site reactions. These reactions include skin-related responses such as itching, rash, and swelling, particularly seen in patients with sensitive skin.
  • A handful of very rare but serious side effects notably include potential thyroid tumors, including cancer, and inflammation of the pancreas (pancreatitis). 

Studies indicate the risk of these side effects doesn't vary significantly among the different GLP-1 RA drugs.

Additional Points

I wanted to quickly address some of the other points in your question.

There generally is no concern when switching from one GLP drug to another, but it may be recommended (at your discretion and that of your provider) to start you at a low dose of your new drug and slowly titrate up. This helps to reduce the severity of side effects.

The jury is still out regarding which GLP has the most positive benefits for treating diabetes, including aspects like lowering blood glucose, reducing body weight, and decreasing the risk of negative cardiovascular events.

In clinical studies, Mounjaro has objectively shown to reduce blood sugar, A1c, and body weight to a greater extent than Trulicity. However, whether or not this improves health outcomes hasn't been definitively determined. These effects are also dose-dependent.

Final Words

Overall, it appears that the side effect profiles for both Mounjaro and Trulicity are remarkably similar.

Therefore, it would be challenging to declare that one is generally more well-tolerated than the other. Ultimately, the suitability of either medication is likely to depend on the individual's unique preferences, bodily responses and other individual factors. I highly suggest speaking to your doctor about what the best choice is for your particular medical situation.

References

  • Trulicity Prescribing Information, Lilly
  • Mounjaro Prescribing Information, AccessFDA
  • A clinical review of GLP-1 receptor agonists: efficacy and safety in diabetes and beyond, PubMed

About the Pharmacist

Dr. Brian Staiger, PharmD

Dr. Brian has been practicing pharmacy for over 13 years and has wide-ranging experiences in many different areas of the profession. From retail, clinical, program development, and administrative responsibilities, he's your knowledgeable and go-to source for all your pharmacy and medication-related questions! Dr. Brian Staiger also has herbalist training and educational certificates in the field of medical ethnobotany. Feel free to send him an email at [email protected]! You can also connect with Dr. Brian Staiger on LinkedIn.

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