Comparison of effectiveness and safety of bexagliflozin and other sodium-glucose cotransporter 2 inhibitors for type 2 diabetes mellitus in adults: systematic review and network meta-analysis of randomized controlled trials.

BACKGROUND

Bexagliflozin exerts definite efficacy in the treatment of type 2 diabetes mellitus (T2DM). However, whether this novel sodium-glucose cotransporter 2 (SGLT2) inhibitor is superior to other SGLT2 inhibitors remains to be elucidated. We therefore performed this network meta-analysis (NMA) to compare bexagliflozin with other SGLT2 inhibitors and establish an efficacy hierarchy in T2DM management.

METHODS

We systematically searched PubMed, Embase, Web of Science and the ClinicalTrials.gov registry for eligible randomized controlled trials (RCTs) published up to January 2026. Statistical analysis was conducted using Stata 14.0. Risk of bias was assessed by the Cochrane tool, evidence certainty was evaluated using the Confidence in Network Meta-Analysis (CINeMA) approach, and intervention ranking was performed using surface under the cumulative ranking curve (SUCRA) values.

RESULTS

This NMA included 48 studies with 26,838 patients. Bexagliflozin significantly reduced HbA1c, fasting plasma glucose (FPG), body weight, systolic blood pressure (SBP) and diastolic blood pressure (DBP) compared with placebo. For HbA1c reduction, canagliflozin (300 mg, 100 mg) and empagliflozin 25 mg were more effective than bexagliflozin, while bexagliflozin was comparable to other SGLT2 inhibitors. For FPG reduction, canagliflozin 300 mg and empagliflozin 25 mg showed slightly greater effects than bexagliflozin, with no significant differences between bexagliflozin and other comparators. Bexagliflozin was superior to dapagliflozin 5 mg but slightly inferior to canagliflozin 300 mg for weight loss, while showing comparable efficacy to other SGLT2 inhibitors. It achieved similar SBP and DBP reduction to other SGLT2 inhibitors, with a significantly greater DBP-lowering effect than empagliflozin 10 mg. Bexagliflozin had a lower incidence of urinary tract infection than dapagliflozin (5 mg, 10 mg), with comparable safety to other agents and placebo. Canagliflozin 300 mg showed the best efficacy for HbA1c, FPG and weight control.

CONCLUSION

Bexagliflozin demonstrates comparable efficacy to most SGLT2 inhibitors in T2DM patients, with a relatively prominent benefit in body weight reduction and a similar safety profile. Canagliflozin 300 mg provides more effective glycemic and weight control.