Effects on clinical outcomes of intensifying triple oral antidiabetic drug (OAD) therapy by initiating insulin versus enhancing OAD therapy in patients with type 2 diabetes: A nationwide population-based, propensity-score-matched cohort study.

Abstract

To compare the effects of initiating insulin as a fourth-line antidiabetic therapy with the effects of enhancing oral antidiabetic drug (OAD) therapy in patients with type 2 diabetes mellitus (T2DM) with triple OAD therapy failure. We conducted a nationwide population-based, retrospective cohort study involving 1022 (without prevalent diabetes-related complications [PDRCs]) and 2077 (with/without PDRCs) propensity score-matched pairs of fourth-line insulin therapy users and enhanced OAD therapy users identified in the period 2004 to 2010. Clinical outcomes including a composite cardiovascular outcome (myocardial infarction, stroke, heart failure or ischaemic heart disease), peripheral vascular disease (PVD), hypoglycaemia and all-cause mortality were assessed up to 2013. Hypoglycaemia was adjusted in Cox models to consider its potential effect on study outcomes. In a T2DM cohort without PDRCs, fourth-line insulin therapy was not associated with greater risks of clinical outcomes, except hypoglycaemia (hazard ratio [HR] 1.45, 95% confidence interval [CI] 1.02-2.07), compared with enhanced OAD therapy. Among patients with T2DM with/without PDRCs, fourth-line insulin therapy was associated with greater risks of the composite cardiovascular outcome (HR 1.23, 95% CI 1.03-1.46), heart failure (HR 1.59, 95% CI 1.12-2.25), ischaemic heart disease (HR 1.37, 95% CI 1.09-1.73), PVD (HR 1.17, 95% CI 1.00-1.36), hypoglycaemia (HR 1.49, 95% CI 1.20-1.85) and all-cause mortality (HR 1.48, 95% CI 1.01-2.17), but adjustment for hypoglycaemia significantly attenuated the risk of heart failure (HR 1.34, 95% CI 0.92-1.94), PVD (HR 1.15, 95% CI 0.98-1.34) and all-cause mortality (HR 1.30, 95% CI 0.84-1.99). Initiation of fourth-line insulin therapy can be considered for patients with T2DM with triple OAD therapy failure, and the importance of awareness and prevention of hypoglycaemia among insulin-treated patients with T2DM cannot be overstated.