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 132 eligible trials enrolled 48 209 participants. 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 -7·98, 95% CI -9·27 to -6·69) followed by GLP-1 receptor agonists (OR 6·33, 95% CI 5·00 to 8·00; MD -5·79, 95% CI -6·34 to -5·25). Naltrexone-bupropion (OR 2·69, 95% CI 2·10 to 3·44), phentermine-topiramate (2·40, 1·68 to 3·44), GLP-1 receptor agonists (2·22, 1·74 to 2·84), and orlistat (1·71, 1·42 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 -11·40, 95% CI -12·51 to -10·29). 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.

IMPORTANCE: Pediatric chronic conditions have become a major public health challenge, and behavioral change plays an important role in overcoming this problem. Many health behavior interventions are described as theory-based, but evidence that such programs properly use theoretical constructs is scant. OBJECTIVE: To identify effective theory-based behavioral interventions that motivate patients and families to adopt better self-management behaviors for chronic disease, to review theoretical constructs from each theory and identify the common elements for action, and to rate the level of evidence for each theory-based chronic disease intervention. EVIDENCE REVIEW: Medline and PsycINFO electronic databases were searched for relevant randomized clinical trial articles published between January 1, 2000, and June 30, 2016, with English language and article type restrictions. These articles reported original data on children and young adults aged 21 years or younger, measured interventions for a pediatric chronic health problem, and assessed the association between interventions and health behavior, knowledge, and outcomes. The Jadad scale was used to evaluate the methods of each article. Articles that explicitly identified the theoretical basis for the intervention and scored 3 points or higher on the Jadad scale were included in the final analysis. FINDINGS: The database search yielded a total of 36187 articles, from which duplicates and those that did not meet the inclusion criteria were eliminated, leaving 129 studies for the full review. Of the 129 studies, 29 (22.5%) had higher Jadad scale scores of 3 or 4 points and underwent the final detailed data abstraction and qualitative synthesis. Five chronic conditions were represented, including asthma (55% [16 of 29]), type 1 diabetes (21% [6 of 29]), obesity (14% [4 of 29]), attention-deficit/hyperactivity disorder (7% [2 of 29]), and autistic spectrum disorder (3% [1 of 29]). Most studies (55% [16 of 29]) used Social Cognitive Theory as the theoretical basis for intervention. The following intervention outcomes were reported: 23 (80%) saw a positive association with health-related behaviors (eg, adherence), 8 (28%) with knowledge, 7 (24%) with attitudes, and 26 (90%) with clinical outcomes. Ten studies (34%) showed results in both health behaviors and health outcomes. Twenty-two studies (76%) demonstrated short-term effects (within 6 months), whereas 12 (41%) reported longer-term changes. CONCLUSIONS AND RELEVANCE: Identifying effective theory-based behavioral interventions can empower those who are involved in the care of children and young adults with chronic conditions.