Effect of SGLT2 Inhibitors on Diabetes Progression in Statin-Treated Patients: A Population-Based Cohort Study

Jack Ssu-Chi Cheng,1,2 Fang‐Ju Lin,1,3,4 Chih-Min Fu,3 Shin‐Yi Lin,3,4 Chih-Yuan Wang,5,6 Hsin-Yi Huang,4,7 Chi-Chuan Wang1,3,4 1Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan; 2Department of Pharmacy, National Taiwan University Cancer Center, Taipei, Taiwan; 3Department of Pharmacy, National Taiwan University Hospital, Taipei, Taiwan; 4School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan; 5Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; 6College of Medicine, National Taiwan University, Taipei, Taiwan; 7Department of Population Medicine, Harvard Medical School, Harvard Pilgrim Health Care Institute, Boston, MA, USACorrespondence: Chi-Chuan Wang, School of Pharmacy, National Taiwan University, Room 202, No. 33, Linsen S. Road, Zhongzheng Dist, Taipei, 100, Taiwan, Tel +886-2-33668739, Fax +886-2-2391-9098, Email [email protected]: Statins, though widely used, may accelerate diabetes progression, necessitating interventions to counteract this effect.Purpose: To compare the effect of sodium-glucose co-transporter 2 inhibitors (SGLT2is) and sulfonylureas or meglitinides on diabetes progression in individuals receiving statins.Patients and Methods: This retrospective cohort study utilized data from the National Health Insurance Research Database of Taiwan. We included patients with diabetes receiving statins and newly initiated SGLT2is or sulfonylureas/meglitinides between July 1, 2016 and December 31, 2020. Diabetes progression was defined as insulin initiation, increase in antidiabetic medication class, or occurrence of new acute hyperglycemic complications. Propensity score matching was used to adjust baseline characteristics. Cox proportional hazards regression was used to calculate the hazard ratios for diabetes progression between users of SGLT2is and those of sulfonylureas or meglitinides. The statistical significance level was set at 0.05 for all analyses.Results: SGLT2i users had a significantly lower risk of diabetes progression compared to sulfonylurea/meglitinide users (HR: 0.53, 95% CI: 0.50– 0.57, p-value < 0.001). Similar results were found in insulin initiation (HR: 0.48, 95% CI: 0.38– 0.61, p-value < 0.001) and increase in antidiabetic medication class (HR: 0.53, 95% CI: 0.50– 0.57, p-value < 0.17). However, the risk of new acute glycemic complications did not significantly differ between groups (HR: 2.47, 95% CI: 0.67– 9.08, p-value = 0.17).Conclusion: SGLT2is may be an effective second-line therapy for statin-treated patients by slowing diabetes progression and potentially mitigating statin-induced metabolic disturbances. Further research, including randomized controlled trials or observational studies with comprehensive laboratory data, is needed to confirm these findings and evaluate their broader applicability.Keywords: SGLT2is, statins, diabetes mellitus, statin-associated diabetes progression