Abstract
PURPOSE The aim of this study was to systematically evaluate the effect of sodium-glucose cotransporter 2 (SGLT2) inhibitor monotherapy on the weight of patients with type 2 diabetes mellitus (T2DM) and to compare different SGLT2 inhibitors with other oral glucose-lowering medications. METHODS PubMed, EMBASE, Cochrane Library, and the ClinicalTrials.gov Web site were searched for relevant randomized controlled trials. Patients with T2DM in the included studies were administered SGLT2 inhibitor monotherapy for at least 12 weeks. The primary outcome was the change in weight from baseline; the secondary outcome was the proportion of patients achieving a weight reduction ≥5%. A pairwise meta-analysis using the DerSimonian-Laird random effects model and a network meta-analysis with Bayesian Markov chain Monte Carlo random effects models were performed. FINDINGS A total of 29 randomized controlled trials (11,999 patients) with a low risk of bias were identified. The results showed that the mean weight loss ranged from -2.26 kg (95% credible interval [CrI], -2.71 to -1.76) with canagliflozin 300 mg to -0.79 kg (95% CrI, -1.54 to -0.05) with ipragliflozin 25 mg compared with metformin. Compared with linagliptin and sitagliptin, the mean weight loss ranged from -3.17 kg (95% CrI, -3.67 to -2.57) with canagliflozin 300 mg to -0.93 kg (95% CrI, -1.92 to 0.05) with ipragliflozin 25 mg. Canagliflozin 300 mg reduced weight to a greater extent than the other SGLT2 inhibitors, with a probability of 99.44%. SGLT2 inhibitors also improved the proportions of patients achieving ≥5% weight loss. The effect of SGLT2 inhibitors on weight reduction was associated with dosage. IMPLICATIONS Available evidence from randomized controlled trials suggests that SGLT2 inhibitor monotherapy exerts more beneficial effects on weight reduction than both metformin and dipeptidyl peptidase 4 inhibitors. The weight reduction effect of 300 mg canagliflozin is greater than that of most other SGLT2 inhibitors. More types of SGLT2 inhibitors in a head-to-head trial, as well as a comparison between SGLT2 inhibitors and glucagon-like peptide 1 receptor agonists, will be involved in our further research. International Prospective Register of Systematic Reviews: CRD42018089761.
