The efficacy and safety of combinations of SGLT2 inhibitors and GLP-1 receptor agonists in the treatment of type 2 diabetes or obese adults: a systematic review and meta-analysis

To evaluate the efficacy and safety of combination therapy with sodium–glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists in the treatment of type 2 diabetes mellitus (T2DM) or obese adults. A meta-analysis was conducted of trials by searching in PubMed, Embase, CENTRAL, Web of Science, and Scopus. A total of five randomized controlled trials (RCTs) and six nonrandomized controlled trials (NCTs) enrolled 1604 participants were identified for meta-analysis. Compared with control/placebo, the combination therapy group had significantly reduced fasting plasma glucose level and 2 h postprandial glucose by 1.28 mmol/L (95% confidence interval [CI]: −1.39, −1.16; p < 0.001) and 1.34 mmol/L (95% CI: −1.47, −1.21; p < 0.001); glycosylated hemoglobin (HbA1c) by 1.32% (95% CI: −1.43, −1.20; p < 0.001); body weight by 0.93 kg (95% CI: −1.04, −0.83; p < 0.001), and systolic blood pressure (SBP) by 1.05 mmHg (95% CI: −1.17, −0.93; p < 0.001). The incidence of genital mycotic infections and urinary infections did not significantly differ from those in the control group, with relative risks (RRs) of 1.67 (95% CI: 0.85, 3.27; p = 0.651) and 1.25 (95% CI: 0.73, 2.15; p = 0.905), respectively. A decreased incidence of cardiovascular events was seen in the combination therapy group (RR = 0.19; 95% CI: 0.04, 0.96; p = 0.403), while an incidence of hypoglycemia was reported (RR = 2.22; 95% CI: 1.20, 4.10; p = 0.71). SGLT2 inhibitors and GLP-1 agonists combination treatment improved glycemic control, reduced body weight, and decreased SBP without an increase in total adverse events or genital and urinary infections in patients with T2DM or obesity.