Macrovascular and microvascular outcomes after beginning of insulin versus additional oral glucose-lowering therapy in people with type 2 diabetes: an observational study

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In type 2 diabetes, the optimal stage to introduce insulin can be unclear. We compared the incidence of subsequent vascular disease between treatment regimens, that is, adding another oral glucose-lowering drug (OGLD) versus starting insulin treatment.


People with poor control on OGLDs who intensified treatment (2000–2007) were grouped by number of baseline OGLDs. Two composite endpoints, of macrovascular disease (all-cause mortality, myocardial infarction, acute coronary syndrome and stroke) and of microvascular disease (peripheral neuropathy, nephropathy or retinopathy), together with HbA1c and weight change over a year, were compared in those beginning insulin versus an additional OGLD. All data came from The Health Information Network UK primary care database.


After exclusions, 14 904 people intensified treatment from one OGLD, 7231 from two and 978 from three, 9, 41 and 90%, respectively, started insulin. Average follow-up was 3.5 years. The adjusted hazard ratios for macrovascular events, OGLD versus insulin, were 0.53 (95%CI 0.42, 0.69) from one baseline treatment, 0.85 (0.70 1.04) from two and 1.07 (0.50, 2.30) from three, with no difference in risk of microvascular disease in any comparison. Mean body weight increased, and mean HbA1c fell across groups; the only significant adjusted comparison was greater weight increase when commencing insulin from one OGLD.


Starting insulin rather than adding another OGLD to double or triple oral therapy did not significantly increase the incidence of vascular events. Beginning insulin from one OGLD was uncommon. More incident macrovascular disease in this group may be caused by residual confounding. Copyright © 2012 John Wiley & Sons, Ltd.

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