SYSTEMATIC REVIEW article
Front. Endocrinol.
Sec. Clinical Diabetes
This article is part of the Research TopicCardiorenal Metabolic Health and Diabetic Nephropathy: Mechanisms, Biomarkers, and Therapeutic AdvancesView all 7 articles
Effects of Different Dosages of Sodium Glucose Transporter 2 Inhibitors on Glucose Level Change in Patients with Type 2 Diabetes Stratified by HbA1c and Renal Function: A Systematic Review and Meta-Analysis
Provisionally accepted
- Department of Endocrinology, Peking Union Medical College Hospital (CAMS), Beijing, China
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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 SGLT2 inhibitors showed a slightly better glycemic control than low-dose SGLT2 inhibitors, with an additional 0.08% (95%CI: -0.12, -0.04) reduction in HbA1c levels. High-dose vs. low-dose SGLT2 inhibitors showed a 0.06%-0.16% further HbA1c reduction across varying glycemia levels (with HbA1c under or over 8%, 8.5%, 9%) and a change in HbA1c levels ranging from -0.07% to 0.04% across varying GFR levels (with GFR under or over 45, 60, 90 ml/min/1.73m²).
Keywords: Baseline HbA1c, Dose-response relationship, Meta-analysis, Renal function, SGLT2 inhibitors
Received: 11 Jan 2026; Accepted: 13 Feb 2026.
Copyright: © 2026 Xiong, Yang, Li and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yuxiu Li
Huabing Zhang
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