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Efficacy and safety of 11 sodium-glucose cotransporter-2 inhibitors at different dosages in type 2 diabetes mellitus patients inadequately controlled with metformin: a Bayesian network meta-analysis

Xu L, Wu Y, Li J, Ding Y, Chow J, Li L, Liu H, Wang Z et al.

BMJ open, 2025

9,144 participants · 8 citations

Abstract

OBJECTIVES: Assess the efficacy and safety profiles of different sodium-glucose cotransporter-2 inhibitors (SGLT2is) as an add-on to metformin in type 2 diabetes mellitus (T2DM) patients.

DESIGN: Bayesian network meta-analysis.

DATA SOURCES: PubMed, Embase, Cochrane Library, Web of Science and ClinicalTrials.gov were searched before 18 December 2024.

ELIGIBILITY CRITERIA: Randomised controlled trials (RCTs) evaluating T2DM patients taking one of 12 SGLT2is as add-on therapy to metformin. Efficacy outcomes focused on glycated haemoglobin (HbA1c) reduction, fasting plasma glucose (FPG) reduction and weight loss (WL). Safety outcomes included adverse events (AEs), serious AEs (SAEs), hypoglycaemia, urinary tract infections (UTI) and genital infections (GI).

DATA EXTRACTION AND SYNTHESIS: Two investigators independently extracted data. The quality of the included studies was assessed using the Cochrane Risk of Bias Tool (V.2.0) for RCTs.

RESULTS: 23 RCTs involving 9144 patients and 11 SGLT2is were included. Compared with placebo, most SGLT2is reduced HbA1c (mean difference (MD), -0.45~-0.80%), FPG (MD, -0.78~-2.02 mmol/L) and body weight (MD, -0.88~-2.67 kg). Only 10 mg of henagliflozin increased the incidence of AEs, and none of the included interventions increased the risks of SAEs or UTIs. 50 mg of empagliflozin exhibited higher risks of hypoglycaemia. Only 10 mg of empagliflozin increased the risk of GI. According to the surface under the cumulative ranking values, SGLT2is…

How strong is the evidence?

Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 9,144 participants or records.

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