Impact of differing glucose-lowering regimens on the pattern of association between glucose control and survival

Currie, Craig J., Holden, Sarah E., Jenkins-Jones, Sara, Morgan, Christopher Ll, Voss, Bernd, Rajpathak, Swapnil N., Alemayehu, Berhanu, Peters, John R. and Engel, Samuel S. 2018. Impact of differing glucose-lowering regimens on the pattern of association between glucose control and survival. Diabetes, Obesity and Metabolism 20 (4) , pp. 821-830. 10.1111/dom.13155

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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 was associated with no difference, or a small increase in mortality risk in regimens with increased risk of hypoglycaemia. Conclusions The pattern of mortality risk across the range of HbA1c differed by glucose‐lowering regimen. Lower HbA1c was associated with increased mortality risk compared with moderate control, especially in those regimens associated with hypoglycaemia. High levels of HbA1c were associated with the expected elevated mortality risk in regimens with low hypoglycaemia risk.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Additional Information:	This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License
Publisher:	Wiley
ISSN:	1462-8902
Date of First Compliant Deposit:	5 July 2018
Date of Acceptance:	4 November 2017
Last Modified:	05 May 2023 21:12
URI:	https://orca.cardiff.ac.uk/id/eprint/112989

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