GLP-1 Side Effects: What the Research Says

GLP-1 Side Effects: What the Research Says

Understanding the side effect profile of GLP-1 medications is an important part of making an informed decision with your doctor. This article draws directly from the published clinical trial data for semaglutide and tirzepatide — without rounding or extrapolating figures. Individual results vary.

Sources Used in This Article

  1. Wilding JPH et al. "Once-Weekly Semaglutide in Adults with Overweight or Obesity." NEJM. 2021;384:989–1002. (STEP 1 trial)
    https://www.nejm.org/doi/10.1056/NEJMoa2032183
  2. Jastreboff AM et al. "Tirzepatide Once Weekly for the Treatment of Obesity." NEJM. 2022;387:205–216. (SURMOUNT-1 trial)
    https://www.nejm.org/doi/10.1056/NEJMoa2206038

Most Common Side Effects: Semaglutide (STEP 1)

As reported in Wilding et al. (2021), gastrointestinal adverse events were the most frequently reported side effects in the semaglutide group. Individual results vary.

  • Nausea: 44.2% of semaglutide participants vs. 16.0% placebo
  • Diarrhoea: 29.7% vs. 15.9% placebo
  • Vomiting: 24.5% vs. 6.3% placebo
  • Constipation: 24.2% vs. 11.1% placebo

All figures above are from Wilding et al., NEJM, 2021. Individual results vary.

Discontinuation Due to Adverse Events: Semaglutide (STEP 1)

As reported in Wilding et al. (2021):

  • 7.0% of semaglutide participants discontinued due to gastrointestinal adverse events, compared to 3.1% in the placebo group. Individual results vary.

Most Common Side Effects: Tirzepatide (SURMOUNT-1)

As reported in Jastreboff et al. (2022), the most frequent adverse events in the tirzepatide groups were also gastrointestinal. Individual results vary.

  • Nausea: reported in 28–33% of tirzepatide participants (across doses) vs. 9% placebo
  • Diarrhoea: reported in 17–22% across doses vs. 11% placebo
  • Vomiting: reported in 10–15% across doses vs. 2% placebo
  • Constipation: reported in 11–17% across doses vs. 6% placebo

All figures above are from Jastreboff et al., NEJM, 2022. Individual results vary.

Discontinuation Due to Adverse Events: Tirzepatide (SURMOUNT-1)

As reported in Jastreboff et al. (2022):

  • Discontinuation due to adverse events occurred in 4.3% (5 mg), 7.1% (10 mg), and 6.2% (15 mg) of tirzepatide participants, compared to 2.6% in the placebo group. Individual results vary.

How GI Side Effects Are Typically Managed

In both trials, gastrointestinal side effects were most common during the dose-escalation phase — when the medication is titrated up gradually — and tended to decrease over time. Gradual dose escalation is a standard approach to reduce the intensity of these effects. Your physician will advise on the appropriate escalation schedule for your situation.

What This Means for Your Programme

Your physician at Bunny will discuss the expected side effect profile before prescribing any medication, and will advise on how to manage any symptoms that arise. You will have access to your care team throughout your programme. These medications are not appropriate for everyone, and your doctor will assess whether the benefit profile is right for your individual situation.

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All medical decisions are made solely by licensed healthcare professionals. Medications are prescribed only when medically necessary. GLP-1 medications are not suitable for everyone. Results may vary.

Results vary. Clinical trial results apply only to the FDA-approved branded medication specifically identified and do not apply to compounded medications. All medications must be prescribed by a licensed provider based on medical necessity.