Network meta-analysis of 58 trials ranks CagriSema third for weight loss behind retatrutide

This is a network meta-analysis of randomised controlled trials in humans; the authors report that 58 trials of 24,214 participants were analysed. The stated objective was to compare the efficacy and safety of glucagon-like peptide 1 based drug treatments for weight loss in adults with overweight or obesity without diabetes.

The authors searched Embase, PubMed (Medline), and Web of Science from 1 January 2000 to 6 March 2026. Eligible trials enrolled adults with overweight or obesity and compared GLP-1 receptor agonists or related co-agonists with placebo or active comparators, with a minimum intervention duration of 12 weeks. Trials enrolling participants with diabetes, or where diabetes status could not be clearly determined, were excluded. The registration number given is PROSPERO CRD420261279841.

Compared with placebo, the authors report that weight loss was greatest with retatrutide (-22.10%, 95% confidence interval -25.60% to -18.60%), followed by tirzepatide (-19.28%, -20.39% to -18.16%), and CagriSema, described in the abstract as a combination of cagrilintide and semaglutide (-17.32%, -19.32% to -15.32%). Conventional GLP-1 receptor agonists showed more modest effects, and similar patterns were seen for waist circumference and lipid outcomes.

On tolerability, the abstract states that low certainty evidence suggested higher rates for discontinuing treatment with danuglipron and retatrutide, whereas mazdutide showed better tolerability. The abstract reports no separate tolerability figure for CagriSema or for cagrilintide alone.

The abstract does not report the dose, frequency, or route of any treatment in the included trials, including cagrilintide or CagriSema. No regimen is stated, so none is listed here.

The authors themselves note that treatment rankings suggested a probabilistic hierarchy favouring next generation incretin based treatments, although confidence intervals overlapped for several comparisons. Their conclusion also flags differences in tolerability, limited head-to-head evidence, and residual uncertainty as factors to consider when interpreting comparative treatment effects.

Structurally, this is a synthesis of other trials rather than new primary data, so the findings inherit the design and reporting of the pooled studies. The tolerability signal is described as low certainty evidence. Trials enrolling participants with diabetes were excluded, so the findings as reported do not speak to that population. The abstract does not state funding sources, author affiliations, or individual trial doses, durations beyond the 12 week minimum, or adverse event counts.

Cagrilintide, coformulated with semaglutide as CagriSema, is not an FDA-approved drug for any use, according to this site's regulatory review rather than the study above.