Fu-Shun YenChih-Cheng HsuYuan-Chih SuJames Cheng-Chung WeiChii-Min Hwu2026-01-302026-01-302021-03-0510.1097/MD.0000000000025085https://scholars.csmu.edu.tw/handle/123456789/4196<jats:sec> <jats:title>Abstract</jats:title> <jats:p>Type 2 diabetes mellitus (T2DM) is a progressive disease. After metformin failure, the addition of insulin or sulfonylureas might increase the risk of hypoglycemia and cardiovascular (CV) morbidity. Here, the risk of all-cause mortality was compared between early insulin treatment and glimepiride use in T2DM patients with background metformin therapy.</jats:p> <jats:p>We conducted a 9-year retrospective cohort study from the population-based National Health Insurance Research Database in Taiwan. A total of 2054 patients with T2DM under insulin or glimepiride treatment were enrolled during 2004 to 2012. Overall event rates of all-cause mortality were compared between 1027 insulin users and 1027 matched glimepiride users.</jats:p> <jats:p>After the propensity score matching, the mortality rates were 72.5 and 4.42 per 1000 person-years for insulin users and glimepiride users. The adjusted hazard ratio of mortality was 14.47 (95% CI: 8.64–24.24; <jats:italic toggle="yes">P</jats:italic> value &lt;.001) as insulin compared with glimepiride users. The insulin users had significantly higher risk of CV death (adjusted hazard ratio 7.95, 95% CI 1.65–38.3, <jats:italic toggle="yes">P</jats:italic> = .01) and noncardiovascular death (adjusted hazard ratio 14.9, 95% CI 8.4–26.3, <jats:italic toggle="yes">P</jats:italic> &lt; .001).</jats:p> <jats:p>The nationwide study demonstrated that metformin plus insulin therapy was associated with higher risk of all-cause mortality.</jats:p> </jats:sec>[SDGs]SDG3journal-article