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What are the side effects of cagrisema?

CagriSema, a fixed‑dose combination of cagrilintide 2.4 mg and semaglutide 2.4 mg for weight loss and type 2 diabetes, has a similar side effect profile to other GLP‑1 receptor agonists. The most common adverse events are gastrointestinal-related, such as nausea, vomiting, constipation, stomach pain, and diarrhea. These side effects are generally mild to moderate and tend to diminish over time.

If it follows FDA-approved GLP‑1 medications like Ozempic/Wegovy (semaglutide) and Mounjaro/Zepbound (tirzepatide), CagriSema will have other side effects such as headache, fatigue, increased heart rate, kidney problems, mental health issues, vision changes, gallbladder problems like gallstones, and an increased risk of thyroid tumors. We can expect to see the results of several new studies looking at CagriSema’s effectiveness and tolerability in the next year to see if this holds true.

What does CagriSema do?

CagriSema is a once-weekly subcutaneous injection that contains two active ingredients: semaglutide and cagrilintide. These medications act on different hormones to help with weight management and blood glucose control.

Semaglutide is a glucagon-like peptide‑1 (GLP‑1) receptor agonist. GLP‑1 is a hormone released in the gut when you eat. It slows digestion, promotes fullness, improves blood sugar control by increasing insulin release, and blocks glucagon release.

Cagrilintide is a long-acting amylin analogue. Amylin is a hormone produced by the pancreas after eating. It increases fullness, slows gastric emptying, and helps regulate blood sugar levels.

The combination of these two medicines has led to significant weight loss and improved glycemic control in adults with obesity or overweight during clinical trials.

Is CagriSema better than Mounjaro?

Several once-weekly injections for weight loss are available, each working slightly differently. CagriSema is the latest contender, but how does it compare?

The SURMOUNT‑5 study (December 2024) compared tirzepatide (Mounjaro/Zepbound) versus semaglutide (Wegovy/Ozempic). After 72 weeks, tirzepatide users lost 20.2% of baseline weight versus 13.7% with semaglutide (a 47% greater relative reduction).

An analysis of 76 trials found CagriSema outperformed tirzepatide for weight loss. The REDEFINE‑1 Phase 3 trial showed 22.7% weight loss over 68 weeks in adults with obesity/overweight (no T2DM), exceeding the 20.2% seen with tirzepatide in SURMOUNT‑5.

Sources

  • Novo Nordisk shares plunge after CagriSema obesity drug trial disappoints. Reuters. Accessed May 29, 2025.
  • Frias, Juan P et al. Efficacy and safety of co‑administered once‑weekly cagrilintide 2.4 mg with once‑weekly semaglutide 2.4 mg in type 2 diabetes: a multicentre, randomised, double‑blind, active‑controlled, phase 2 trial. The Lancet, Volume 402, Issue 10403, 720–730. Accessed May 29, 2025.
  • Novo Nordisk A/S: CagriSema demonstrates superior weight loss in adults with obesity or overweight and type 2 diabetes in the REDEFINE 2 trial. Novo Nordisk. Accessed May 29, 2025.
  • Yao H et al. Comparative effectiveness of GLP‑1 receptor agonists on glycaemic control, body weight, and lipid profile for type 2 diabetes: systematic review and network meta-analysis. BMJ. 2024 Jan 29;384:e076410. Accessed May 29, 2025.