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

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.

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.

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.

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.