Sunday, 21 July, 2024
HomeEditor's PickPharmacotherapy more effective than lifestyle change for weight loss – Systematic review

Pharmacotherapy more effective than lifestyle change for weight loss – Systematic review

Of all the available medications for treatment of overweight and obesity, phentermine–topiramate and GLP-1 receptor agonists proved the best drugs, found a systematic review and network meta-analysis of randomised controlled trials in The Lancet. Of the GLP-1 agonists, semaglutide might be the most effective.

A team of researchers from Sichuan University in China examined data from 143 clinical trials, with a total of 49,801 participants, that assessed the proportion of patients who achieved at least a 5% weight reduction on different medications compared with lifestyle interventions.

Every medication studied, except levocarnitine, was more effective than lifestyle interventions at helping patients achieve at least a 5% weight reduction, researchers report in The Lancet. Compared with lifestyle interventions, phentermine-topiramate was the most effective for meeting this weight loss benchmark (odds ratio 8.02), followed by glucagon-like peptide 1 (GLP-1) receptor agonists (OR 6.33).

“Clinicians and adults who might need weight-lowering drugs could discuss the benefits and harms and make a shared decision based on their values and preferences,” said lead study author Dr Sheyu Li, an associate professor of endocrinology and metabolism at Sichuan University in Chengdu, China.

“Phentermine-topiramate and GLP-1 receptor agonists showed the best weight-lowering effects, but it does not mean that most people should use it without considering their individualised context,” Li added.

When the researchers examined three GLP-1 receptor agonists separately, they found the largest likelihood of a weight reduction of 5% or more relative to lifestyle interventions with semaglutide (OR 9.82), followed by liraglutide (OR 4.91), and exenatide (OR 2.86).

Compared with lifestyle interventions, participants were also significantly more likely to experience at least a 10% weight loss with semaglutide (OR 13.32), followed by phentermine-topiramate (OR 9.74), and naltrexone- bupropion (OR 5.19).

Mean weight change from baseline was greatest with semaglutide (-11.41%), followed by phentermine-topiramate (-7.97%), liraglutide (-4.68%), and naltrexone-bupropion (-4.11%).

Odds of discontinuation due to adverse events were largest with naltrexone-bupropion (OR 2.69), liraglutide (OR 2.45), and phentermine-topiramate (OR 2.40). The certainty of the evidence varied across studies and for the different medications included in the analysis. The highest level of certainty was for mean weight change from baseline and the odds of achieving a 5% or 10% weight reduction with phentermine-topiramate, GLP-1 receptor agonists as a class, and semaglutide.

One limitation of the study was the lack of individual patient data pooling, the authors note, and another, the wide variation in study population characteristics and duration of follow-up for weight loss endpoints.

Although the aim was to assess the effectiveness of medication relative to lifestyle interventions, lifestyle interventions still have a key role in weight management, Li said.

“One should never recommend a weight-lowering drug before advising a sound and practical lifestyle modification strategy. Meanwhile, for people with extremely severe obesity, bariatric surgery may be a lifesaving choice that (has) more priority than medication.”

Study details

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

Qingyang Shi, Yang Wang, Qiukui Hao, Prof Per Olav Vandvik, Prof Gordon Guyatt, Jing Li, Zhe Chen, Shishi Xu, Yanjiao Shen, Prof Long Ge, Prof Feng Sun, Ling Li, Jiajie Yu, Kailei Nong, Xinyu Zou, Siyi Zhu, Cong Wang, Shengzhao Zhang, Zhi Qiao, Zhongyu Jian, Ya Li, Xinyi Zhang, Kerun Chen, Furong Qu, Yuan Wu, Yazhou He, Prof Haoming Tian, Sheyu Li.

Published in The Lancet on 8 December 2021.

Summary

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.

The Lancet article – Pharmacotherapy for adults with overweight and obesity: a systematic review and network meta-analysis of randomised controlled trials (Open access)

 

See more from MedicalBrief archives:

 

Significant weight-loss with weekly injections of novel amylin agent — Phase 2 trial

 

STEP 2 trial: Semaglutide hope for patients with type 2 diabetes

 

Maintenance semaglutide injections led to continued weight loss — STEP 4

 

Fierce debate over a new theory to tackle the global obesity pandemic

 

 

 

MedicalBrief — our free weekly e-newsletter

We'd appreciate as much information as possible, however only an email address is required.