Effects of different dosages of Sodium-glucose cotransporter 2 inhibitors on glucose level change in patients with type 2 diabetes stratified by HbA1c and renal function: a systematic review and meta-analysis
Abstract
Background: Type 2 diabetes mellitus (T2DM) is a major global health challenge due to high cardiovascular risk. Sodium-glucose cotransporter 2 (SGLT2) inhibitors can offer glycemic and cardiorenal benefits. Most agents are available in low and high doses, with the assumption that higher doses improve glycemic control. However, previous evidence shows only marginal hemoglobin A1c (HbA1c) reduction (≈0.08-0.18%) with high doses, raising uncertainty about their clinical necessity. Patient factors such as baseline HbA1c and renal function influence SGLT2 efficacy, but whether these factors modify dose response remains unclear. This study evaluates dose-dependent effects across HbA1c and renal function strata.
Objective: To assess the glycemic impact of high- versus low-dose SGLT2 inhibitors in T2DM, stratified by HbA1c and renal function.
Methods: This analysis followed PRISMA guidelines (PROSPERO ID: CRD42024605351). PubMed, the Cochrane Library, and EMBASE were systematically searched for randomized controlled trials involving SGLT2 inhibitors in adults with T2DM through November 24, 2024. The primary outcome was change in glycated hemoglobin, stratified by hemoglobin A1c (HbA1c) and glomerular filtration rate (GFR) levels. Subgroup analyses were performed based on different SGLT2 inhibitors and dosages.
Results: A total of 23 studies were included for the meta-analysis. Seventeen studies (n = 7,021) were stratified by HbA1c, and eight (n = 7,998) by GFR. Overall, high-dose…
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: 7,998 participants or records.
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