Comparative Effectiveness of CagriSegma, Semaglutide, Cagrilintide and Tirzepatide in the Management of Overweight and Obesity: A Network Meta-Analysis of Randomized Clinical Trials

In a network meta-analysis of 25 randomized trials, tirzepatide 15 mg and CagriSema produced the largest body-weight reductions, at about 17.8–18.0%, followed by semaglutide 7.2 mg at 14.66%; all treatments increased gastrointestinal adverse events, but serious adverse events were similar to placebo.

Observational study — Network meta-analysis of randomized controlled trials. Population: Adults with overweight or obesity. Sample size: 25 trials. Interventions: CagriSema; Semaglutide 7.2 mg; Tirzepatide 15 mg; Cagrilintide.

Twenty-five trials involving 12 interventions were included. Tirzepatide 15 mg resulted in the greatest percent weight reduction (MD -17.97%), followed by CagriSema (MD -17.84%) and semaglutide 7.2 mg (MD -14.66%). At the ≥20% weight-loss threshold, CagriSema showed marked superiority (RR 27.82), followed by tirzepatide 15 mg (RR 23.70). Gastrointestinal adverse events increased with all treatments (RR 1.33–1.91), and treatment discontinuation was highest with semaglutide 7.2 mg (RR 3.09). Serious adverse events remained comparable to placebo across all regimens.

Researchers studying Cagrilintide, Semaglutide, or Tirzepatide would use this paper for comparative evidence on weight-loss efficacy and safety across these agents. It supports dual-pathway and combination incretin therapies as options for substantial weight loss, but it does not provide direct head-to-head trial data or long-term comorbidity outcomes, and it offers no individualised treatment recommendations.

Key findings

• Tirzepatide 15 mg showed the greatest percent weight reduction (mean difference -17.97%), followed by CagriSema (-17.84%) and semaglutide 7.2 mg (-14.66%).
• At the ≥20% weight-loss threshold, CagriSema had a relative risk of 27.82 and tirzepatide 15 mg of 23.70, indicating marked superiority over placebo.
• Gastrointestinal adverse events increased with all treatments (relative risk 1.33 to 1.91).
• Treatment discontinuation was highest with semaglutide 7.2 mg (relative risk 3.09).
• Serious adverse events remained comparable to placebo across all regimens.

Limitations

• No direct head-to-head trials comparing all agents were included, so comparisons are indirect.
• As a network meta-analysis, results may be affected by heterogeneity across trials in dosing, populations, and outcome definitions.
• The abstract does not report long-term outcomes or patient-level comorbidity data.
• Relative safety and effectiveness between active treatments is less certain than comparisons against placebo.

The record

• Journal: Endocrinology, diabetes & metabolism 9(4): e70248
• Published: 2026-06-01
• PMID: 42207966 — DOI: 10.1002/edm2.70248
• MeSH terms: Humans, Obesity, Weight Loss, Gastric Inhibitory Polypeptide, Anti-Obesity Agents, Treatment Outcome, Overweight, Glucagon-Like Peptide 1, Glucagon-Like Peptides, Randomized Controlled Trials as Topic, Tirzepatide, Semaglutide
• Author countries: Jordan, USA

Peptide profiles: Cagrilintide, Semaglutide, Tirzepatide.

All indexed evidence: Cagrilintide trials & papers, Semaglutide trials & papers, Tirzepatide trials & papers.

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