Sodium-glucose co-transporter 2 inhibitors improve insulin resistance and β-cell function in type 2 diabetes: A meta-analysis.

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are widely used for the treatment of type 2 diabetes (T2D).

Aim: To evaluate the influence of SGLT2 inhibitors on homeostasis model assessment of insulin resistance (HOMA-IR) and β-cell function (HOMA-β) in patients with T2D in a meta-analysis.

Methods: Randomized controlled trials (RCTs) comparing SGLT2 inhibitors to placebo in T2D patients, with a minimum treatment duration of 12 weeks, were searched using the PubMed, EMBASE, and Cochrane Library databases. Risk of bias was assessed using the Cochrane Risk of Bias Tool, and the certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. Changes in HOMA-IR and HOMA-β were the outcomes analyzed. Meta-analyses were performed using a random-effects model by incorporating the potential influences of heterogeneity.

Results: Of 1388 articles identified, 24 RCTs met the inclusion criteria. 23 of the included studies were double-blind RCTs with low risk of bias. Pooled results including 2272 patients showed that SGLT2 inhibitors significantly reduced HOMA-IR compared to placebo [mean difference (MD) = -0.81, 95% confidence interval (CI): -1.11 to -0.52, < 0.001; = 82%], indicating reduced insulin resistance. Additionally, meta-analysis with 2845 patients suggested that SGLT2 inhibitors significantly increased HOMA-β (MD = 7.90, 95%CI: 5.44-10.37, < 0.001; = 74%) compared to placebo in patients with T2D, indicating improved β-cell function. Based on GRADE assessment, the certainty of evidence was rated moderate for both outcomes due to heterogeneity. Subgroup analyses showed that HOMA-β increased more substantially in non-Asian studies than in Asian studies ( for subgroup difference < 0.01). Subgroup analyses according to the individual medications of SGLT2 inhibitors all showed significant improvement of HOMA-IR and HOMA-β ( all < 0.05). No significant publication bias was detected ( for Egger's test all > 0.05).

Conclusion: SGLT2 inhibitors are associated with improvements in insulin resistance and β-cell function in patients with T2D, although the certainty of evidence is moderate due to heterogeneity.