Novel Amylin-Based Therapies for Weight Management in Adults With Overweight or Obesity Without Diabetes: A Network Meta-Analysis.
High dose CagriSema led to a significant weight loss of -17.18% compared to placebo, but findings are based on low-certainty data and require further validation.
Where it sits
this study against the rest of the cagrilintide (am833) corpusSummary and findings
This study evaluated the effects of long-acting amylin-based therapies (ABTs) on weight management in adults with overweight or obesity without diabetes. The primary outcome measured was the percent change in body weight from baseline, with a total of 4642 participants across six trials. The results indicated that high dose CagriSema led to a mean difference of -17.18% in body weight compared to placebo.
Abstract
Background Long-acting amylin-based therapies (ABTs) are emerging anti-obesity agents; we sought to compare their effects on weight and anthropometric outcomes in adults with overweight/obesity without diabetes, evaluate gastrointestinal (GI) safety, and rank agents and doses within a network meta-analysis (NMA) framework. Methods We conducted a frequentist random-effects NMA of randomized controlled trials comparing novel ABTs with placebo or active comparators in R. Primary outcome was the percent change in body weight from baseline. Secondary outcomes included absolute weight changes, anthropometric measures, and overall and specific GI adverse events (AEs). Treatments (including dose strata) were compared with placebo within a single network and ranked using P scores. Results Six trials (N = 4642; 12-68 weeks) were included. Compared with placebo, high dose (HiD) subcutaneous amycretin produced the largest reduction in percent body weight (mean difference -23.95%; P score 1.00), followed by HiD eloralintide (-18.01%; P score 0.89) and HiD CagriSema (-17.18%; P score 0.85), all exceeding semaglutide 2.4 mg (-11.45%) and liraglutide 3.0 mg (-6.4%). Almost similar patterns were observed for absolute weight, body mass index, waist circumference and categorical weight-loss thresholds. GI AEs, nausea, vomiting and constipation were more common with HiD ABTs, especially oral amycretin and CagriSema, while diarrhoea mainly increased with semaglutide 2.4 mg. Only HiD CagriSema increased AE-related discontinuation. Conclusions Novel ABTs, such as HiD amycretin, CagriSema and eloralintide, may induce substantial short- to medium-term weight loss but may also increase GI AEs; given sparse, low-certainty data, these findings are preliminary and require confirmation in larger trials. Trial registration The meta-analysis was registered in PROSPERO (CRD420261340457). The review protocol summary can be accessed at the PROSPERO website (https://www.crd.york.ac.uk/PROSPERO/view/CRD420261340457).
Background
The paper addresses the clinical question of how effective novel amylin-based therapies, such as Cagrilintide, are for weight management in adults with overweight or obesity who do not have diabetes. Previous research has indicated that amylin analogs may play a role in appetite regulation and weight loss, but comprehensive comparisons of their efficacy have been limited. This study is significant as it seeks to synthesize existing data to provide a clearer understanding of these therapies' relative effectiveness.
Methods
This study utilized a network meta-analysis design to compare multiple amylin-based therapies for weight management. The specific population, sample size, dosing information, and duration of treatment were not reported in the abstract. The primary and secondary outcome measures were not specified, which limits the understanding of the analysis's focus.
Results
Not reported in abstract.
Interpretation
Without specific results reported in the abstract, it is challenging to compare the findings of this study to prior literature or to assess the clinical significance of any observed effects. The lack of detailed methodology and results raises concerns about the robustness of the conclusions and the potential for confounding factors to influence the outcomes.
Key findings
- Not reported in abstract.
Limitations
- Not reported in abstract.
- No specific numeric findings provided.
- Lack of detail on study design and methodology.
- No information on sample size or duration of treatment.