Pharmacotherapy for weight loss in adults with type 2 diabetes: a systematic review of randomised controlled trials

Background: Clinically significant weight loss improves glycaemic control and cardiovascular disease risk in patients with type 2 diabetes (T2DM). Aim: To identify and assess the efficacy of medical treatments for weight loss in adults with T2DM. Methods: A systematic review was conducted of peer-reviewed literature between July 2004 and July 2020 via PubMed, Embase, Web of Science, medRxiv and Cochrane Central Register of Controlled Trials. Randomised controlled trials (RCTs) in English investigating medical treatments for weight loss in patients with T2DM were included. RCTs of pharmacotherapy withdrawn from the market were excluded. No minimum length of follow-up time was established. Outcomes of interest were changes from baseline in body weight (%), changes from baseline in HbA(1c) (%, mmol/mol) and proportion of patients who achieved >= 5% weight loss. Quality assessment was evaluated using the Jadad score. Results: Fifteen RCTs were included with a total of 4,207 participants with T2DM. Interventions included medications approved for obesity management (orlistat, liraglutide, naltrexone-bupropion and phentermine-topiramate) and other agents investigated for the primary purpose of weight loss (topiramate, metreleptin, dapagliflozin and exenatide) compared with placebo. The duration of the intervention varied from 12 to 56 weeks. Placebo-adjusted body weight loss ranged from 2.2% to 7.3%. Furthermore, 30.5-77.0% of patients achieved >= 5% weight loss. Placebo-adjusted change in glycated haemoglobin was 0.3-1.5% (3.3-16.4 mmol/mol). Conclusion: Current evidence demonstrates that pharmacotherapy for weight loss, except for leptin, is associated with weight loss and glycaemic improvement in patients with T2DM.