Risk of mortality and adverse cardiovascular outcomes in type 2 diabetes: a comparison of patients treated with sulfonylureas and metformin

Abstract

Aims/hypothesis: The aim of this study was to evaluate the risk of adverse cardiovascular outcomes in patients with type 2 diabetes newly treated with sulfonylureas and metformin. Subjects and methods: The Diabetes Audit and Research in Tayside Scotland (DARTS) diabetes information system and the Medicines Monitoring Unit (MEMO) dispensed prescribing database for the population of Tayside, Scotland (400,000 people) were employed. Patients newly prescribed with oral hypoglycaemic agents between 1994 and 2001 were classified into five study cohorts according to the treatment received: metformin only, sulfonylureas only, sulfonylureas added to metformin, metformin added to sulfonylureas, and both drugs simultaneously. In Cox regression analyses, we estimated relative risks for all-cause mortality, cardiovascular mortality and cardiovascular hospital admission for patients in the five study cohorts, with metformin monotherapy as the reference group. Results: Of the 5,730 study patients, 1,000 died during a maximum of 8 years follow-up. Patients in the sulfonylureas only cohort had increased risks of mortality and cardiovascular mortality, with unadjusted relative risks of 3.12 (95% CI 2.54-3.84) and 3.71 (95% CI 2.64-5.22), respectively. After adjusting for differences between groups (age, sex, duration of diabetes, blood pressure, cholesterol, HbA 1c , smoking, previous hospital admission, treatment with cardiovascular medication), these relative risks were 1.43 (95% CI 1.15-1.77) and 1.70 (95% CI 1.18-2.45), respectively. Patients in the combination cohorts had significantly increased risks of cardiovascular hospital admission, as well as increased risks of mortality and cardiovascular mortality. Conclusions/interpretation: In this cohort study of patients newly treated with oral hypoglycaemic agents, those treated with sulfonylureas only, or combinations of sulfonylureas and metformin, were at higher risk of adverse cardiovascular outcomes than those treated with metformin alone.

Megatrials in type 2 diabetes. From excitement to frustration?

“…These results are in agreement with large retrospective analyses. In the survey of Evans et al [18], in spite of similar glycaemic control (HbA 1c~8 %), the mortality rate was lower for metformin than for sulfonylur-eas, with the combination of the two producing an intermediate rate. Among the older adults of the Cardiovascular Health Study [19], a greater mortality rate was observed for those treated with insulin compared with those on oral hypoglycaemic agents, even though there was no apparent difference between these two subgroups in terms of fasting plasma glucose (~10 mmol/l).…”

Dietary Interventions to Extend Life Span and Health Span Based on Calorie Restriction

“…In humans, metformin supplementation has been shown to reduce adiposity (40) and mortality rates in diabetic individuals, most effectively in obese and insulin-resistant individuals (41)(42)(43). Although the data so far are promising, further study is needed to show whether metformin is able to extend life span in healthy rodents, primates, and humans.…”

Comment on: Evans JMM, Ogston SA, Emslie-Smith A, Morris AD (2006) Risk of mortality and adverse cardiovascular outcomes in type 2 diabetes: a comparison of patients treated with sulfonylureas and metformin. Diabetologia 49:930–936

“…In their recent article in Diabetologia, Evans et al demonstrated that the unadjusted risk of cardiovascular mortality with sulfonylurea monotherapy was 3.71 compared with metformin monotherapy [1]. After adjusting for differences between groups, the relative risk of cardiovascular mortality was 1.70 (95% CI 1.18-2.45).…”