Marc Claesen1, Pieter Gillard1, Frank De Smet1, Michiel Callens1, Bart De Moor1, Chantal Mathieu1. 1. STADIUS Center for Dynamical Systems (M.Cl., B.D.M.), Signal Processing and Data Analytics, Department of Electrical Engineering, iMinds Medical IT, (M.Cl., B.D.M.), and Department of Public Health and Primary Care (F.D.S.), KU Leuven, B-3000 Leuven, Belgium; Department of Clinical and Experimental Medicine (P.G., C.M.), University of Leuven-KUL and University Hospitals Leuven, B-3000 Leuven, Belgium; and Department of Medical Management (F.D.S., M.Ca.), National Alliance of Christian Mutualities, B-1090 Brussels, Belgium.
Abstract
CONTEXT: Several observational studies and meta-analyses have reported increased mortality of patients taking sulfonylurea and insulin. The impact of patient profiles and concomitant therapies often remains unclear. OBJECTIVE: The objective of the study was to quantify survival of patients after starting glucose-lowering agents (GLAs) and compare it with control subjects, matched for risk profiles and concomitant therapies. DESIGN: This was a retrospective, controlled, cohort study. SETTING: The study is based on health expenditure records of the largest Belgian health mutual insurer, covering more than 4.4 million people. PATIENTS: A total of 115 896 patients starting metformin, sulfonylurea, or insulin (alone or in combination) between January 2003 and December 2007 participated in the study. Control subjects without GLA therapy were matched for age, gender, history of cardiovascular events, and therapy with antihypertensives, statins and blood platelet aggregation inhibitors. INTERVENTION(S): There were no interventions. MAIN OUTCOME MEASURE: Five-year survival after the start of GLA was measured. RESULTS: Profiles of patients using different GLAs varied, with patients on sulfonylurea being oldest and patients on insulin having more frequently a history of cardiovascular disease. Excess mortality differed across GLA therapies compared with matched controls without GLAs, even after adjusting for observable characteristics. Only metformin monotherapy was not associated with an increased 5-year mortality compared with matched controls, whereas individuals on a combination of sulfonylurea and insulin had the highest mortality risks. Age and concomitant use of statins strongly affect survival. CONCLUSIONS: Differences exist in 5-year survival of patients on GLA, at least partly driven by the risk profile of the individuals themselves. Metformin use was associated with lowest 5-year mortality risk and statins dramatically lowered 5-year mortality throughout all cohorts.
CONTEXT: Several observational studies and meta-analyses have reported increased mortality of patients taking sulfonylurea and insulin. The impact of patient profiles and concomitant therapies often remains unclear. OBJECTIVE: The objective of the study was to quantify survival of patients after starting glucose-lowering agents (GLAs) and compare it with control subjects, matched for risk profiles and concomitant therapies. DESIGN: This was a retrospective, controlled, cohort study. SETTING: The study is based on health expenditure records of the largest Belgian health mutual insurer, covering more than 4.4 million people. PATIENTS: A total of 115 896 patients starting metformin, sulfonylurea, or insulin (alone or in combination) between January 2003 and December 2007 participated in the study. Control subjects without GLA therapy were matched for age, gender, history of cardiovascular events, and therapy with antihypertensives, statins and blood platelet aggregation inhibitors. INTERVENTION(S): There were no interventions. MAIN OUTCOME MEASURE: Five-year survival after the start of GLA was measured. RESULTS: Profiles of patients using different GLAs varied, with patients on sulfonylurea being oldest and patients on insulin having more frequently a history of cardiovascular disease. Excess mortality differed across GLA therapies compared with matched controls without GLAs, even after adjusting for observable characteristics. Only metformin monotherapy was not associated with an increased 5-year mortality compared with matched controls, whereas individuals on a combination of sulfonylurea and insulin had the highest mortality risks. Age and concomitant use of statins strongly affect survival. CONCLUSIONS: Differences exist in 5-year survival of patients on GLA, at least partly driven by the risk profile of the individuals themselves. Metformin use was associated with lowest 5-year mortality risk and statins dramatically lowered 5-year mortality throughout all cohorts.
Authors: Derek LeRoith; Geert Jan Biessels; Susan S Braithwaite; Felipe F Casanueva; Boris Draznin; Jeffrey B Halter; Irl B Hirsch; Marie E McDonnell; Mark E Molitch; M Hassan Murad; Alan J Sinclair Journal: J Clin Endocrinol Metab Date: 2019-05-01 Impact factor: 5.958