Impact of differing glucose-lowering regimens on the pattern of association between glucose control and survival
Abstract
AIMS: To characterize survival in relation to achieved glycated haemoglobin (HbA1c) level within alternative glucose-lowering regimens with differing risks of hypoglycaemia.
METHODS: Data were extracted from the UK Clinical Practice Research Datalink and the corresponding Hospital Episode Statistics. Patients with type 2 diabetes prescribed glucose-lowering therapy in monotherapy or dual therapy with metformin between 2004 and 2013 were identified. Risk of all-cause mortality within treatment cohorts was evaluated using the Cox proportional hazards model, introducing mean HbA1c as a quarterly updated, time-dependent covariable.
RESULTS: There were 6646 deaths in a total follow-up period of 374 591 years. Survival for lower (<7%) vs moderate HbA1c levels (≥7%, <8.5%) differed by cohort: metformin, adjusted hazard ratio (aHR) 1.03 (95% confidence interval [CI] 0.95-1.12); sulphonylurea, aHR 1.11 (95% CI 0.99-1.25); insulin, aHR 1.47 (95% CI 1.25-1.72); combined regimens with low hypoglycaemia risk, aHR 1.02 (95% CI 0.94-1.10); and combined regimens with higher hypoglycaemia risk excluding insulin, aHR 1.24 (95% CI 1.13-1.35) and including insulin, aHR 1.28 (95% CI 1.18-1.37). Higher HbA1c levels were associated with increased mortality in regimens with low hypoglycaemia risk. Post hoc analysis by HbA1c deciles revealed an elevated risk of all-cause mortality for the lowest deciles across all cohorts, but particularly in those regimens associated with hypoglycaemia. High HbA1c…
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Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence.
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