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

Area of Science:

• Endocrinology
• Pharmacology
• Metabolic Diseases

Background:

• Sulfonylureas (SUs) are common type 2 diabetes mellitus (T2DM) treatments but often lose effectiveness due to declining beta-cell function.
• Sodium-glucose co-transporter 2 (SGLT2) inhibitors offer an insulin-independent mechanism for glucose lowering, potentially improving long-term glycemic control.

Purpose of the Study:

• To compare the long-term glycemic durability of SGLT2 inhibitors versus SUs in T2DM patients on metformin.
• To evaluate HbA1c changes over extended periods in head-to-head randomized controlled trials (RCTs).

Main Methods:

• Meta-analysis of five RCTs with seven comparisons, focusing on head-to-head trials of SGLT2 inhibitors versus SUs in T2DM patients receiving metformin.
• Inclusion criteria required reporting of HbA1c at intermediate and final time points (minimum 96 weeks follow-up).
• Random-effects models were used to calculate pooled mean differences (MD) and 95% confidence intervals (CIs).

Main Results:

• SGLT2 inhibitors showed significantly smaller increases in HbA1c compared to SUs over time (e.g., -0.28% from 24-28 weeks to 96-104 weeks).
• Sustained glycemic benefits of SGLT2 inhibitors were observed in longer-term analyses, from 52 weeks to 208 weeks (MD: -0.22%) and 104 weeks to 208 weeks (MD: -0.12%).
• All comparisons demonstrated high statistical significance (p < 0.001 or p = 0.04) with zero heterogeneity (I² = 0%).

Conclusions:

• SGLT2 inhibitors provide superior long-term glycemic durability compared to SUs in T2DM patients treated with metformin.
• These findings support the preferential use of SGLT2 inhibitors as a second-line therapy option after metformin.
• The consistent efficacy and durability highlight SGLT2 inhibitors as a valuable therapeutic class for T2DM management.