Key result
Choice of sulfonylurea (glimepiride, glipizide, or glyburide) combined with metformin did not significantly influence overall mortality risk (e.g., glimepiride vs glipizide HR 1.03; 95% CI 0.89-1.20).
Why the study?
Does the choice of sulfonylurea combined with metformin affect overall mortality in patients with Type 2 diabetes?
Cohort (n=7,320)
Does the choice of sulfonylurea combined with metformin affect overall mortality in patients with Type 2 diabetes?
Effect estimate: HR 1.03 (glimepiride vs glipizide), HR 1.08 (glimepiride vs glyburide), HR 1.05 (glipizide vs glyburide) (95% CI 0.89-1.20, 0.90-1.30, 0.95-1.15)
The choice of sulfonylurea (glimepiride, glipizide, or glyburide) when combined with metformin does not substantially influence overall mortality risk in patients with Type 2 diabetes.
Sulfonylurea choice with metformin shows no mortality difference; leaves open whether RCTs would alter selection in type 2 diabetes.
AIMS: Sulfonylureas have been shown to increase mortality when used in combination with metformin. This may not be a class effect of sulfonylureas, but rather secondary to differences in properties inherent to the individual sulfonylureas (hypoglycaemic risk, sulfonylurea receptor selectivity and effects on myocardial ischemic preconditioning). The purpose of this study was to assess the risk of overall mortality in patients with Type 2 diabetes treated with different combinations of sulfonylureas and metformin. METHODS: A retrospective cohort study was conducted using an academic health center enterprise-wide electronic health record system to identify 7320 patients with Type 2 diabetes (3768 initiators of glyburide (glibenclamide) and metformin, 2277 initiators of glipizide and metformin and 1275 initiators of glimepiride and metformin), ≥ 18 years of age and not on insulin or a non-insulin injectable at baseline. The patients were followed for mortality by documentation in the electronic health record and Social Security Death Index. Multivariable Cox models with propensity analysis were used to compare cohorts. RESULTS: No statistically significant difference in overall mortality risk was observed among the different combinations of sulfonylureas and metformin: glimepiride and metformin vs. glipizide and metformin (HR 1.03; 95% CI 0.89-1.20), glimepiride and metformin vs. glyburide (glibenclamide) and metformin (HR 1.08; 95% CI 0.90-1.30), or with glipizide and metformin vs. glyburide (glibenclamide) and metformin (HR 1.05; 95% CI 0.95-1.15). CONCLUSIONS: Our results did not identify an increased mortality risk among the different combinations of sulfonylureas and metformin, suggesting that overall mortality is not substantially influenced by the choice of sulfonylurea.
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Pantalone et al. (2012) conducted a cohort in Type 2 diabetes (n=7,320). Glimepiride and metformin vs. Glipizide and metformin or glyburide and metformin was evaluated on Overall mortality (HR 1.03 (glimepiride vs glipizide), HR 1.08 (glimepiride vs glyburide), HR 1.05 (glipizide vs glyburide), 95% CI 0.89-1.20, 0.90-1.30, 0.95-1.15). Choice of sulfonylurea (glimepiride, glipizide, or glyburide) combined with metformin did not significantly influence overall mortality risk (e.g., glimepiride vs glipizide HR 1.03; 95% CI 0.89-1.20).
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