Pharmacotherapy for adults with overweight and obesity: a systematic review and network meta-analysis of randomised controlled trials

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Background

Pharmacotherapy provides an option for adults with overweight and obesity to reduce
their bodyweight if lifestyle modifications fail. We summarised the latest evidence
for the benefits and harms of weight-lowering drugs.

Methods

This systematic review and network meta-analysis included searches of PubMed, Embase,
and Cochrane Library (CENTRAL) from inception to March 23, 2021, for randomised controlled
trials of weight-lowering drugs in adults with overweight and obesity. We performed
frequentist random-effect network meta-analyses to summarise the evidence and applied
the Grading of Recommendations Assessment, Development, and Evaluation frameworks
to rate the certainty of evidence, calculate the absolute effects, categorise interventions,
and present the findings. The study was registered with PROSPERO, CRD 42021245678.

Findings

14 605 citations were identified by our search, of which 143 eligible trials enrolled
49 810 participants. Except for levocarnitine, all drugs lowered bodyweight compared
with lifestyle modification alone; all subsequent numbers refer to comparisons with
lifestyle modification. High to moderate certainty evidence established phentermine–topiramate
as the most effective in lowering weight (odds ratio [OR] of ≥5% weight reduction
8·02, 95% CI 5·24 to 12·27; mean difference [MD] of percentage bodyweight change −7·97,
95% CI −9·28 to −6·66) followed by GLP-1 receptor agonists (OR 6·33, 95% CI 5·00 to
8·00; MD −5·76, 95% CI −6·30 to −5·21). Naltrexone–bupropion (OR 2·69, 95% CI 2·11
to 3·43), phentermine–topiramate (2·40, 1·69 to 3·42), GLP-1 receptor agonists (2·17,
1·71 to 2·77), and orlistat (1·72, 1·44 to 2·05) were associated with increased adverse
events leading to drug discontinuation. In a post-hoc analysis, semaglutide, a GLP-1
receptor agonist, showed substantially larger benefits than other drugs with a similar
risk of adverse events as other drugs for both likelihood of weight loss of 5% or
more (OR 9·82, 95% CI 7·09 to 13·61) and percentage bodyweight change (MD −11·41,
95% CI −12·54 to −10·27).

Interpretation

In adults with overweight and obesity, phentermine–topiramate and GLP-1 receptor agonists
proved the best drugs in reducing weight; of the GLP-1 agonists, semaglutide might
be the most effective.

Funding

1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University.

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