Abstract
Introduction To conduct the first meta-analysis of randomized controlled trials (RCTs) comparing glucagon-like peptide 1 receptor agonists (GLP-1RAs) with sodium-glucose cotransporter 2 inhibitors (SGLT-2is) for obese type 2 diabetes (T2D) patients uncontrolled on metformin. Methods We searched Pubmed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Ovid, and Web of Science from inception to May 14, 2020, without language restrictions for eligible RCTs. The primary outcome is the mean change from baseline in glycated haemoglobin (HbA1c). Results Totally, 3 RCTs enrolled 2066 patients were identified. Compared with SGLT-2is, treatment with GLP-1RAs achieved significant reduced HbA1c by 0.40% (95% CI: −0.54, −0.25; p < 0.00001), fasting blood glucose (FBG) by 0.17 mmol/L (95% CI: −0.31, −0.04; p=0.01), and postprandial blood glucose (PBG) by 0.32 mmol/L (95% CI: −0.49, −0.14; p=0.0003) for obese T2D patients uncontrolled on metformin. The significant benefit of weight loss was seen in semaglutide (MD: −0.75; 95% CI: −1.18, −0.31; p < 0.0007). No significant difference was detected between GLP-1RAs and SGLT-2is in overall adverse events (RR: 1.03; 95% CI: 0.98, 1.09; p=0.76), but gastrointestinal events showed higher occurrence in GLP-1RAs groups compared with SGLT-2is (RR: 1.62; 95% CI: 1.37, 1.93; p < 0.00001). Subgroup analyses revealed that follow-up time did not statistically influence glycemic control. Conclusion GLP-1RAs are superior to SGLT-2is for obese T2D patients uncontrolled on metformin in glycemic control without an increase in adverse events except for a higher occurrence in gastrointestinal events. Future large longer-term follow-up clinical trials are needed to provide more evidence about the sustainable effects and safety of GLP-1RAs compared with SGLT-2is.
Highlights
To conduct the first meta-analysis of randomized controlled trials (RCTs) comparing glucagon-like peptide 1 receptor agonists (GLP-1RAs) with sodium-glucose cotransporter 2 inhibitors (SGLT-2is) for obese type 2 diabetes (T2D) patients uncontrolled on metformin
Current evidences make the treatment option clear in T2D patients with established cardiovascular disease (CVD) or chronic kidney disease (CKD) [6, 12]; it remains obscure which one is better for obese T2D patients uncontrolled on metformin
Us, this study aims to conduct a systematic review and meta-analysis of RCTs to compare the efficacy and safety outcomes of GLP-1RAs and SGLT-2is for obese T2D patients uncontrolled on metformin
Summary
Type 2 diabetes (T2D), the most common type of diabetes, is recognized as the “disaster of the 21st century” by the World Health Organization (WHO) [1, 2]. Us, this study aims to conduct a systematic review and meta-analysis of RCTs to compare the efficacy and safety outcomes of GLP-1RAs and SGLT-2is for obese T2D patients uncontrolled on metformin. RCTs were considered eligible for inclusion if they (1) recruited T2D patients who showed inadequate response to stable and optimized metformin monotherapy, with a body mass index ≥30 kg/m2, (2) compared the efficacy and safety outcomes of GLP-1RAs with SGLT-2is directly, (3) reported the mean change in glycated haemoglobin (HbA1c) from baseline, and (4) had a follow-up time for at least 12 weeks. Two authors independently assessed the risk of selection, detection, performance, reporting, and attrition bias of RCTs with Cochrane Collaboration’s tool [18]. Sensitivity analysis was performed for the primary outcome by excluding one trial at a time to make sure the stability of the results
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