Meta-Analysis
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Jul 15, 2025; 16(7): 107335
Published online Jul 15, 2025. doi: 10.4239/wjd.v16.i7.107335
Sodium-glucose co-transporter 2 inhibitors improve insulin resistance and β-cell function in type 2 diabetes: A meta-analysis
Shang-Yu Chai, Ru-Ya Zhang, Zhi-Yuan Ning, Yi-Man Zheng, Rajpathak Swapnil, Li-Nong Ji
Shang-Yu Chai, Ru-Ya Zhang, Zhi-Yuan Ning, Yi-Man Zheng, Value and Implementation Global Medical and Scientific Affairs, MSD China, Shanghai 200030, China
Rajpathak Swapnil, Value and Implementation Outcomes Research, MRL, Merck and Co., Inc., Rahway, NJ 19454, United States
Li-Nong Ji, Department of Endocrinology, People’s Hospital of Peking University, Beijing 100044, China
Author contributions: Chai SY and Zhang RY conceived, designed, or planned the study; Chai SY collected or assembled the data and wrote the initial draft; Chai SY, Zhang RY, Ning ZY and Ji LN performed or supervised analyses; Zheng YM and Swapnil R interpreted the results; Chai SY Zheng YM obtained funding; All authors provided substantive suggestions for revision or critically reviewed, and approved final version of the paper, and agreed to be accountable for all aspects of the work.
Conflict-of-interest statement: Chai SY, Zhang RY, Ning ZY and Zheng YM are employees of MSD China; Swapnil R is employee of Merck Sharp and Dohme LLC., a subsidiary of Merck and Co., Inc., Rahway, NJ, United States. However, the study was conducted independently, and the funding source had no influence on data selection, analysis, or manuscript preparation. The authors affirm that the results and conclusions of the study were derived objectively and free from external bias.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Li-Nong Ji, MD, Professor, Department of Endocrinology, People’s Hospital of Peking University, No. 11 Xizhimen South Street, Xicheng District, Beijing 100044, China. jiln@bjmu.edu.cn
Received: March 21, 2025
Revised: April 10, 2025
Accepted: June 10, 2025
Published online: July 15, 2025
Processing time: 116 Days and 21.7 Hours
Abstract
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, P < 0.001; I2 = 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, P < 0.001; I2 = 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 (P 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 (P all < 0.05). No significant publication bias was detected (P 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.

Keywords: β-cell function; Homeostasis model assessment; Insulin resistance; Meta-analysis; Sodium-glucose co-transporter 2 inhibitors

Core Tip: This meta-analysis, based on 24 randomized controlled trials, showed that sodium-glucose cotransporter 2 (SGLT2) inhibitors significantly improve insulin resistance and β-cell function in patients with type 2 diabetes (T2D), as evidenced by reductions in homeostasis model assessment of insulin resistance and increases in β-cell function. These findings highlight the potential of SGLT2 inhibitors to alleviate insulin resistance and improve β-cell function beyond glucose lowering. These results provide novel insights into the therapeutic role of SGLT2 inhibitors in managing T2D and underscore their ability to modify disease progression by targeting key pathophysiological mechanisms.