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. Issue 2 (11th October 2018) - Kuo, Shihchen
Abstract : Aims: 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. Materials and methods: 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. Results: 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). Conclusions: 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.