Effectiveness of SGLT2 inhibitors compared to sulphonylureas for long-term glycemic control in type 2 diabetes: A meta-analysis.

Abstract

Sulphonylureas (SUs) are common glucose-lowering agents used for managing type 2 diabetes mellitus (T2DM). However, their long-term effectiveness is often limited due to declining β-cell function. Sodium-glucose co-transporter 2 (SGLT2) inhibitors act independently of insulin, potentially providing more sustained glycemic control. Nonetheless, comparative data regarding the long-term glycemic durability of these two drug classes are limited. We performed a meta-analysis of head-to-head randomized controlled trials (RCTs) comparing the efficacy of SGLT2 inhibitors versus SUs in patients with T2DM already receiving metformin therapy. Eligible studies reported HbA1c values at intermediate (24-28 weeks or 48-52 weeks) and final (96-104 weeks or 208 weeks) time points, with a minimum follow-up duration of 96 weeks. Pooled mean differences (MD) and their 95% confidence intervals (CIs) were calculated using random-effects models. Seven comparisons from five RCTs were included in our analysis. Compared with SUs, SGLT2 inhibitors were associated with significantly smaller increases in HbA1c over time. From 24-28 weeks to 96-104 weeks, the pooled MD was -0.28% (95% CI: -0.35 to -0.20; p < 0.001; I² = 0%). From 48-52 weeks to 96-104 weeks, the MD was -0.11% (95% CI: -0.19 to -0.04; p = 0.004; I² = 0%). In longer-term analyses, SGLT2 inhibitors demonstrated sustained benefits from 52 weeks to 208 weeks (MD: -0.22%; 95% CI: -0.34 to -0.10; p < 0.001) and from 104 weeks to 208 weeks (MD: -0.12%; 95% CI: -0.25 to -0.01; p = 0.04). Overall, SGLT2 inhibitors provide superior glycemic durability compared to SUs in patients with T2DM, supporting their preferential use as a second-line therapy after metformin.