Cardiometabolic risk effects of weight-loss medications: An updated network meta-analysis.

AIMS: As a result of the withdrawal of lorcaserin and the approval of tirzepatide and semaglutide, we conducted a new network meta-analysis to assess the overall and comparative effects of six US Food and Drug Administration (FDA)-approved weight-loss medications on the cardiometabolic risk profile of obese adults, and to find out which of these medications is best in improving cardiometabolic risk factors. MATERIALS AND METHODS: We searched our databases for randomised clinical trials of the effects of weight-loss drugs approved by the FDA as of April 2024 in obese adults taking them for 1 year or more, compared with placebo or between the agents. We performed pairwise and network meta-analyses, and the results were reported as weighted and standardised mean differences. RESULTS: A total of 31 trials with 24 792 participants were included in this network meta-analysis. The quality of evidence was rated as moderate in most cases using the GRADE. Compared with placebo, the weight-loss drugs resulted in moderate reductions in fasting glucose of 11.12 mg/dL (95% CI, -13.70, -8.53), glycosylated haemoglobin of 0.60% (95% CI, -0.75, -0.45) and waist circumference of 5.28 cm (95% CI, -6.57, -4.00), with minimal or modest benefits of clinical relevance in blood pressure and cholesterol profile. In addition, we found tirzepatide to be relatively good overall in comparisons between drugs. CONCLUSIONS: This study found that six FDA-approved weight-loss drugs had a moderately beneficial effect on the cardiometabolic risk profile. In general, tirzepatide was more effective than other pharmacological agents in improving cardiometabolic risk factors.