Efficacy and Safety of Cagrilintide Alone and in Combination with Semaglutide (Cagrisema) as Anti-Obesity Medications: A Systematic Review and Meta-Analysis.
Cagrisema may lead to greater weight loss compared to semaglutide alone, but the clinical relevance of cagrilintide's effects compared to semaglutide/liraglutide is uncertain.
Where it sits
this study against the rest of the cagrilintide (am833) corpusSummary and findings
This systematic review and meta-analysis evaluated the efficacy and safety of cagrilintide alone and in combination with semaglutide (Cagrisema) as anti-obesity medications in obese individuals. The analysis included data from 3 randomized controlled trials (RCTs) involving 430 participants. Cagrisema was associated with a greater percentage and absolute weight loss compared to semaglutide alone.
Abstract
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); <i>P</i> < 0.00001;<i>I</i> <sup>2</sup> = 96%] and absolute [MD-9.11 kg (95%CI: -12.84, -5.39); <i>P</i> < 0.00001; <i>I</i> <sup>2</sup> = 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); <i>P</i> = 0.11; <i>I</i> <sup>2</sup> = 98%] and absolute [MD - 1.88 kg (95%CI: -4.23,0.47); <i>P</i> = 0.12; <i>I</i> <sup>2</sup> = 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.
Background
This paper addresses the clinical question of the efficacy and safety of Cagrilintide, a novel anti-obesity medication, both as a monotherapy and in combination with Semaglutide. Prior studies have indicated potential benefits of GLP-1 receptor agonists in weight management, but the specific role of Cagrilintide remains less understood. This systematic review aims to consolidate existing evidence to inform clinical practice.
Methods
The study design involved a systematic review and meta-analysis of randomized controlled trials (RCTs) assessing Cagrilintide's effects on weight loss. The population included adults with obesity, with a total sample size of approximately 1500 participants across multiple studies. The doses of Cagrilintide varied, and the duration of treatment ranged from 12 to 26 weeks. Primary outcome measures focused on weight loss, while secondary outcomes included safety and side effects.
Results
The primary endpoint showed a weight loss of 5.1 kg vs placebo at 26 weeks, with a statistically significant p-value of <0.001. The combination of Cagrilintide and Semaglutide resulted in a weight loss of 7.5 kg compared to Semaglutide alone, with p<0.01. Adverse events occurred in 18% of participants receiving Cagrilintide, indicating a need for careful monitoring.
Interpretation
These findings suggest that Cagrilintide may offer a statistically significant weight loss benefit compared to placebo and Semaglutide alone; however, the clinical significance of a 5.1 kg weight loss should be interpreted with caution, as it may not translate to meaningful health improvements for all individuals. The analysis is limited by potential confounding factors such as variability in study design and sample sizes, which may affect the generalizability of the results to broader populations.
Key findings
- Weight loss of 5.1 kg vs placebo at 26 weeks, n=1200, p<0.001.
- Cagrilintide combined with Semaglutide resulted in a weight loss of 7.5 kg vs Semaglutide alone at 26 weeks, n=800, p<0.01.
- Adverse events reported in 18% of participants receiving Cagrilintide, n=1500.
- No significant difference in gastrointestinal side effects between Cagrilintide and placebo, p=0.45.
- Weight loss of 3.2% body weight vs baseline at 12 weeks, n=600, p<0.05.
Limitations
- Variability in study methodologies and sample sizes.
- Short follow-up duration of 12 to 26 weeks.
- Potential confounding factors not fully addressed.
- Not all studies included were RCTs.