Wang H, Cordiner RLM, Huang Y, Donnelly L, Hapca S, Collier A, McKnight J, Kennon B, Gibb F, McKeigue P, Wild SH, Colhoun H, Chalmers J, Petrie J & Sattar N (2023) Cardiovascular Safety in Type 2 Diabetes With Sulfonylureas as Second-line Drugs: A Nationwide Population-Based Comparative Safety Study. Diabetes Care, 46 (5), pp. 967-977. https://doi.org/10.2337/dc22-1238
To assess the real-world cardiovascular (CV) safety for sulfonylureas (SU), in com-parison with dipeptidyl peptidase 4 inhibitors (DPP4i) and thiazolidinediones (TZD), through development of robust methodology for causal inference in a whole nation study.
RESEARCH DESIGN AND METHODS
A cohort study was performed including people with type 2 diabetes diagnosed in Scotland before 31 December 2017, who failed to reach HbA1c 48 mmol/mol despite metformin monotherapy and initiated second-line pharmacotherapy (SU/DPP4i/TZD) on or after 1 January 2010. The primary outcome was composite major adverse cardiovascular events (MACE), including hospitalization for myo-cardial infarction, ischemic stroke, heart failure, and CV death. Secondary outcomes were each individual end point and all-cause death. Multivariable Cox proportional hazards regression and an instrumental variable (IV) approach were used to control confounding in a similar way to the randomization process in a randomized control trial.
Comparing SU to non-SU (DPP4i/TZD), the hazard ratio (HR) for MACE was 1.00 (95% CI: 0.91–1.09) from the multivariable Cox regression and 1.02 (0.91–1.13) and 1.03 (0.91–1.16) using two different IVs. For all-cause death, the HR from Cox regression and the two IV analyses was 1.03 (0.94–1.13), 1.04 (0.93–1.17), and 1.03 (0.90–1.17).
Our findings contribute to the understanding that second-line SU for glucose low-ering are unlikely to increase CV risk or all-cause mortality. Given their potent ef-ficacy, microvascular benefits, cost effectiveness, and widespread use, this study supports that SU should remain a part of the global diabetes treatment portfolio
Advanced and Specialized Nursing; Endocrinology, Diabetes and Metabolism; Internal Medicine
Additional co-authors: Thomas MacDonald; Rory J. McCrimmon; Daniel R. Morales; Ewan R. Pearson; Scottish Diabetes Research Network Epidemiology Group
Diabetes Care: Volume 46, Issue 5
|Publication date online||21/03/2023|
|Date accepted by journal||26/01/2023|
|Publisher||American Diabetes Association|