Glucagon-like peptide-1 receptor agonists or sodium-glucose cotransporter-2 inhibitors as add-on therapy for patients with type 2 diabetes? A systematic review and meta-analysis of surrogate metabolic endpoints

Objective. - As sodium-glucose cotransporter-2 inhibitors (SGLT-2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) are second-line treatment options in type 2 diabetes mellitus (T2DM), our study sought to provide precise effect estimates regarding the role of GLP-1RAs vs SGLT-2is as add-on treatments in patients uncontrolled by metformin monotherapy. Research design and methods. - PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL) and 'grey literature' were searched from their inception up to December 2019 for randomized controlled trials (RCTs) with durations >= 12 weeks to evaluate the safety and efficacy of adding a GLP-1RA vs an SGLT-2i in patients with T2DM. Results. - Three eligible RCTs were identified. Administration of GLP-1RAs vs SGLT-2is resulted in significant decreases in HbA1c with no significant impact on either body weight or fasting plasma glucose. GLP-1RA treatment led to a significant increase in odds for achieving an HbA1c < 7% compared with SGLT-2is, whereas no difference was detected in body weight reductions of > 5%. Significantly greater risk for any hypoglycaemia, nausea and diarrhoea, and lower risk for genital infections, was also observed with GLP-1RAs, while no differences regarding severe hypoglycaemia, treatment discontinuation and impact on blood pressure levels were identified. No other major safety issues arose. Conclusion. - Our meta-analysis suggests that GLP-1RAs provide better glycaemic effects than SGLT-2is in patients with T2DM uncontrolled by metformin, albeit while increasing risk for hypoglycaemia and gastrointestinal adverse events. (C) 2020 Elsevier Masson SAS. All rights reserved.