Effect of Sglt2 Inhibitor Drugs on Triglyceride-Glucose (Tyg) Index in Adults: A Systematic Review and Meta-Analysis Publisher Pubmed



Hazaveh M B ; Naseri Rad F ; Ghadri H ; Kakoienejad M M ; Emami Alorizy S M ; Bahrami O ; Goudarzimehr L ; Heidari A ; Eslami S ; Goodarzy B ; Vaseghi Y ; Rafatnia A ; Yarahmadi D
Source: Primary Care Diabetes Published:2026

Abstract

Background Insulin resistance is a serious public health concern. The triglyceride-glucose (TyG) index is a simple, cheap, and reproducible surrogate of insulin resistance, and sodium-glucose cotransporter-2 (SGLT2) inhibitors have reshaped cardio-metabolic care beyond glycemic control. Methods We followed PRISMA and registered the protocol in PROSPERO (CRD420251056341). We searched PubMed, Scopus, Web of Science, EMBASE, and Cochrane from inception to May 31st, 2026, including observational studies and clinical trials reporting baseline and follow-up TyG in adults. Two reviewers screened records, a third resolved disagreements, data were extracted with a standardized form, and quality was assessed with Cochrane RoB 2.0, the Newcastle-Ottawa Scale, and the JBI checklists. The primary outcome was within-group change in TyG pooled with random-effects (Hartung-Knapp); tests were two-sided with a significance threshold of 0.05. Results Twelve studies comprising thirteen study arms were included, with a total of 1845 participants. Follow-up ranged from 12 weeks to 5 years. Across studies, SGLT2 inhibitor therapy was associated with a significant reduction in TyG index (mean difference = −0.28, 95% confidence interval [-0.41; −0.14], I2 = 99.5%). Egger’s test suggested possible small-study effects, whereas Begg’s test and trim-and-fill analysis did not show clear evidence of publication bias; leave-one-out analyses showed that no single study materially influenced the pooled estimate. Conclusion Despite heterogeneity in populations, drug choice, and follow-up duration, SGLT2 inhibitors were associated with a significant decrease in TyG, although small-study effects cannot be excluded. © 2026 Primary Care Diabetes Europe.