Efficacy and Safety of Cagrilintide Alone and in Combination with Semaglutide (Cagrisema) as Anti-Obesity Medications: A Systematic Review and Meta-Analysis.
This systematic review and meta-analysis examined the weight-loss efficacy and safety of cagrilintide (an amylin analogue) alone and in combination with semaglutide 2.4 mg (referred to as "Cagrisema") compared to placebo or active comparators (semaglutide or liraglutide) in adults with obesity. Researchers searched electronic databases and identified 3 eligible randomized controlled trials encompassing 430 participants. The pooled analysis found that Cagrisema was associated with significantly greater percentage and absolute body weight reduction compared to semaglutide 2.4 mg alone over 20–32 weeks, though with notably high statistical heterogeneity (I² up to 98%). Cagrilintide monotherapy showed statistically similar weight loss to semaglutide or liraglutide over 26–32 weeks. Regarding safety, treatment-emergent and serious adverse events were broadly comparable across groups; however, gastrointestinal adverse events and vomiting were significantly more frequent with Cagrisema versus semaglutide, while vomiting was significantly lower with cagrilintide monotherapy versus semaglutide or liraglutide. Key limitations include the very small number of included trials (n=3), limited total sample size, short-to-medium follow-up durations, and very high heterogeneity, which tempers confidence in the pooled estimates.
Why this grade: Although the analysis pools data from RCTs in humans, confidence is substantially limited by only 3 included trials, a total sample of 430 participants, very high heterogeneity (I² up to 98%), and relatively short follow-up durations.
No meta-analysis has analysed role of cagrilintide as weight-loss medication in obese individuals. Electronic databases were searched for RCTs involving obese individuals receiving cagrilintide or cagrilintide-2.4 mg with semaglutide-2.4 mg combination (Cagrisema) compared to placebo/active comparator. Primary outcomes were changes in body weight; secondary outcomes were alterations in glycemia, lipids, and adverse events. From 678 articles, data from 3 RCTs involving 430 individuals were analysed. At 20-32 weeks, patients receiving Cagrisema weekly had significantly greater percentage [mean difference (MD)-9.07% (95%CI: -11.91, -6.23); P I 2 = 96%] and absolute [MD-9.11 kg (95%CI: -12.84, -5.39); P I 2 = 98%] weight-loss, compared to semaglutide 2.4 mg weekly. At 26-32 weeks, cagrilintide 2.4 mg had a similar percentage [MD - 1.83% (95%CI: -4.08, -0.42); P = 0.11; I 2 = 98%] and absolute [MD - 1.88 kg (95%CI: -4.23,0.47); P = 0.12; I 2 = 98%] weight-loss, compared to semaglutide/liraglutide. Treatment-emergent and serious adverse events were comparable between groups. Gastrointestinal adverse events and vomiting were significantly higher with Cagrisema compared to semaglutide. Vomiting was significantly lower with cagrilintide compared to semaglutide/liraglutide. Cagrisema outperforms semaglutide regarding weight loss. Cagrilintide shows comparable weight loss to semaglutide/liraglutide with significantly lower vomiting.
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