Comparison of Effects of Dipeptidyl Peptidase-4 Inhibitors and Sulfonylureas in Combination with Metformin: A Hospital-Based Cohort Study of Patients With Type 2 Diabetes

Jui Wang; Kuo-Liong Chien; Hon-Yen Wu

doi:10.1016/j.clinthera.2025.06.001

Comparison of Effects of Dipeptidyl Peptidase-4 Inhibitors and Sulfonylureas in Combination with Metformin: A Hospital-Based Cohort Study of Patients With Type 2 Diabetes

Clin Ther. 2025 Jun 26:S0149-2918(25)00205-X. doi: 10.1016/j.clinthera.2025.06.001. Online ahead of print.

Authors

Jui Wang¹, Kuo-Liong Chien², Hon-Yen Wu³

Affiliations

¹ Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei City, Taiwan; Health Data Research Center, National Taiwan University, Taipei City, Taiwan.
² Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei City, Taiwan; Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei City, Taiwan.
³ Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei City, Taiwan; Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei City, Taiwan; Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan; Department of Medical Research, Far Eastern Memorial Hospital, New Taipei City, Taiwan; School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei City, Taiwan. Electronic address: honyenwu@ntu.edu.tw.

PMID: 40579267
DOI: 10.1016/j.clinthera.2025.06.001

Abstract

Purpose: The influence of dipeptidyl peptidase-4 inhibitors (DPP4i) on clinical parameters in patients with type 2 diabetes (T2DM) remain controversial. This study compared the effects of DPP4i versus sulfonylureas (SU) on glucose, lipid, and renal profiles among patients with T2DM.

Methods: In this retrospective cohort study, we used the Integrated Medical Database of National Taiwan University Hospital (NTUH-iMD) to identify patients aged ≥40 years with T2DM diagnosed between 2008 and 2016. Using propensity score matching at a ratio of 1:1, we matched patients who received DPP4i with those who received SU as add-on therapy to metformin. The primary outcomes were changes in blood levels of clinical profiles, including hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), total cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol, creatinine, and estimated glomerular filtration rate.

Findings: A total of 475 matched pairs of DPP4i and SU users were followed for a mean duration of 2.0 years. Both DPP4i and SU significantly reduced HbA1c, FPG, TC, TG, and LDL-C. Compared with SU, DPP4i showed a borderline greater reduction in HbA1c (effect estimate for the change of levels = -0.12%; 95% confidence interval (CI), -0.24% to 0%) and a nonsignificant difference in FPG (effect estimate for the change of levels = -4.09 mg/dL; 95% CI, -8.54 to 0.36 mg/dL).

Implications: Both DPP4i and SU improve glucose and lipid control in T2DM patients on metformin. DPP4i showed a modest advantage in improving glycemic control, suggesting it may be a preferred second-line therapy over SU.

Keywords: Cohort study; Dipeptidyl peptidase-4 inhibitors; Hemoglobin A1c; Sulfonylureas.