Aims: To describe the relative health and economic outcomes associated with different second-line therapeutic approaches to manage glycaemia in older type 2 diabetes patients requiring escalation from metformin monotherapy. Materials and methods: The Clinical Practice Research Datalink database was used to inform a retrospective observational cohort study of patients with type 2 diabetes treated with metformin monotherapy requiring escalation (addition or switch) to a second-line oral regimen

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... om January 1, 2008 to December 31, 2014. Primary outcomes included time to first event (any event, myocardial infarction [MI], stroke, or composite of MI/stroke [major adverse cardiovascular event; MACE]) and total event rate. The health economic consequences associated with the choice of second-line treatment in older patients were assessed using the CORE Diabetes Model. Results: A total of 10 484 patients were included; the majority escalated to second-line treatment with metformin + sulphonylurea (SU; 42%) or switched to SU monotherapy (28%). In multivariate adjusted analyses, total event rates for MACE with metformin + dipeptidyl peptidase-4 (DPP-4) inhibitor were significantly lower than with metformin + SU (0.61, 95% confidence interval [CI] 0.39-0.98), driven by a lower MI rate in the metformin + DPP-4 inhibitor group (0.52, 95% CI 0.27-0.99). Economic analyses estimated that metformin + DPP-4 inhibitor treatment was associated with the largest gain in health benefit, and cost-effectiveness ratios were favourable (<£30 000 per quality-adjusted life-year) for all second-line treatment scenarios. Conclusions: With respect to treatment choice, data from the present study support the notion of prescribing beyond metformin + SU, as alternative regimens have been shown to be associated with reduced outcomes risk and value for money. K E Y W O R D S management, metformin, older patients, second-line, type 2 diabetes