Amylin-based obesity therapy: a meta-analysis of Cagrilintide and CagriSema versus placebo.
Cagrilintide and CagriSema show promise for weight loss and cardiometabolic improvements in obesity, but further research is needed to confirm long-term benefits and safety.
Where it sits
this study against the rest of the cagrilintide (am833) corpusSummary and findings
This meta-analysis evaluated the efficacy and safety of Cagrilintide and its combination with semaglutide, CagriSema, in adults with overweight or obesity. Cagrilintide monotherapy significantly reduced body weight by 6.08% and 5.89 kg, while CagriSema reduced body weight by 5.98% and 4.68 kg and waist circumference by 10.91 cm. Both treatments were associated with modest increases in adverse events.
Abstract
<h4>Background</h4>Obesity remains a major global health challenge, driving demand for effective pharmacotherapies. Cagrilintide, a once-weekly amylin receptor agonist, and its fixed-dose combination with semaglutide (CagriSema) represent novel therapeutic approaches. This systematic review and meta-analysis evaluated their efficacy and safety in adults with overweight or obesity.<h4>Methods</h4>Four databases were searched from inception to March 2026. Eligible randomized controlled trials (RCTs) assessed Cagrilintide monotherapy or CagriSema versus placebo. Outcomes included percentage and absolute body weight change, waist circumference, blood pressure, HbA1c, and adverse events. Data were pooled using random-effects models in RevMan, with results expressed as mean differences (MD) or risk ratios (RR) with 95% confidence intervals.<h4>Results</h4>Four RCTs encompassing 5425 participants were included. Cagrilintide monotherapy produced significant reductions in body weight (MD: -6.08%; MD: -5.89 kg) and blood pressure, without meaningful HbA1c improvement. CagriSema significantly reduced body weight (MD: -5.98%; MD: -4.68 kg), waist circumference (MD: -10.91 cm), systolic blood pressure, and HbA1c. Both treatments showed modest but statistically significant increases in adverse events. Substantial heterogeneity was observed across most outcomes.<h4>Conclusion</h4>Cagrilintide-based therapies produce clinically meaningful weight loss and cardiometabolic improvements. CagriSema demonstrates additional glycemic benefits over monotherapy. Larger, longer-duration trials are needed to confirm long-term efficacy and safety.
Background
Obesity is a significant global health issue, necessitating effective pharmacotherapies. Cagrilintide, an amylin receptor agonist, and its combination with semaglutide (CagriSema) are emerging treatments. This study evaluates their potential in reducing body weight and improving cardiometabolic parameters, addressing a critical need for effective obesity management.
Methods
The meta-analysis included randomized controlled trials comparing Cagrilintide or CagriSema to placebo. Four databases were searched up to March 2026, identifying four RCTs with 5425 participants. Outcomes measured included body weight change, waist circumference, blood pressure, HbA1c, and adverse events. Data were analyzed using random-effects models, with results expressed as mean differences or risk ratios with 95% confidence intervals.
Results
Cagrilintide monotherapy resulted in significant body weight reductions of 6.08% and 5.89 kg. CagriSema also significantly reduced body weight by 5.98% and 4.68 kg, and waist circumference by 10.91 cm. While CagriSema improved HbA1c, Cagrilintide did not show meaningful glycemic changes. Both treatments were associated with modest increases in adverse events. Substantial heterogeneity was noted across most outcomes.
Interpretation
The findings suggest that Cagrilintide and CagriSema offer clinically meaningful weight loss and cardiometabolic benefits, with CagriSema providing additional glycemic improvements. However, the substantial heterogeneity and short duration of the included trials limit the generalizability of these results. Larger and longer-duration studies are needed to confirm these findings and assess long-term safety.
Key findings
- Cagrilintide monotherapy: -6.08% body weight, -5.89 kg
- CagriSema: -5.98% body weight, -4.68 kg
- CagriSema: -10.91 cm waist circumference
- Modest increases in adverse events for both treatments
- Substantial heterogeneity across outcomes
Limitations
- Substantial heterogeneity across outcomes
- Short duration of included trials
- Potential for publication bias
- Modest increases in adverse events