Comparative Weight Loss With CagriSema, Semaglutide, Cagrilintide, and Tirzepatide

Key Takeaways

• Tirzepatide 15 mg and CagriSema showed the strongest overall weight-loss signals in this indirect comparison of randomized trials.
• At the at least 20% weight-loss threshold, CagriSema ranked first and tirzepatide 15 mg ranked second.
• Gastrointestinal adverse events increased across treatments, discontinuation was highest with semaglutide 7.2 mg, and serious adverse events were comparable to placebo.

In adults with overweight or obesity, tirzepatide 15 mg showed the largest pooled percent weight reduction at MD -17.97% in a network meta-analysis of randomized clinical trials published in Endocrinology, Diabetes & Metabolism.

This analysis searched PubMed, Scopus, and Cochrane Central for randomized controlled trials. Eligible studies compared tirzepatide, semaglutide, cagrilintide, and CagriSema with placebo in adults with overweight or obesity. Twenty-five trials involving 12 interventions met inclusion criteria, and the investigators used a random-effects network meta-analysis. Reported outcomes included percent body weight, absolute weight, waist circumference, BMI, thresholds from at least 5% through at least 20% weight loss, HDL-C, and safety outcomes. No direct head-to-head studies had compared all advanced anti-obesity medications.

For percent body-weight change, CagriSema and semaglutide 7.2 mg followed tirzepatide 15 mg, with MD values of -17.84% and -14.66%, respectively. That ranking placed tirzepatide 15 mg and CagriSema ahead of the other reported regimens in the pooled network. At the at least 20% weight-loss threshold, CagriSema ranked first at RR 27.82, followed by tirzepatide 15 mg at RR 23.70. At least 5% weight loss improves metabolic parameters, while at least 10% is linked to meaningful comorbidity reduction. These threshold findings added context beyond average percent change alone.

Safety findings showed a consistent gastrointestinal adverse-event burden across treatments, with relative risks ranging from 1.33 to 1.91. Treatment discontinuation was highest with semaglutide 7.2 mg, at RR 3.09, while serious adverse events were comparable to placebo across regimens.

The authors concluded that tirzepatide 15 mg and CagriSema achieved the greatest weight reduction. They described treatment selection as individualized according to comorbidity burden, tolerability, and weight-loss goals. They also stated that future head-to-head trials are needed to clarify comparative performance.