Patients: Veterans who initiated metformin or sulfonylurea therapy for diabetes. Patients with chronic kidney disease or serious medical illness were excluded.
Measurements: Composite outcome of hospitalization for acute myocardial infarction or stroke, or death...
...crude rates of the composite outcome were 18.2 per 1000 person-years in sulfonylurea users and 10.4 per 1000 person-years in metformin users (adjusted incidence rate difference, 2.2 [95% CI, 1.4 to 3.0] more CVD events with sulfonylureas per 1000 person-years; adjusted hazard ratio [aHR], 1.21 [CI, 1.13 to 1.30]). Results were consistent for both glyburide (aHR, 1.26 [CI, 1.16 to 1.37]) and glipizide (aHR, 1.15 [CI, 1.06 to 1.26]) in subgroups by CVD history, age, body mass index, and albuminuria; in a propensity score–matched cohort analysis; and in sensitivity analyses.
According to the authors and the editors it cannot be said whether metformin confers macrovascular benefit, sulfonylureas cause macrovascular harm or both. In the 1970s the University Group Diabetes Program (UGDP) study showed macrovascular harm attributable to sulfonylurea therapy and the class of agents has since carried a black box warning. The UKPDS also suggested superior outcomes with metformin including specifically the macrovascular outcome of stroke.
The authors of the cohort study cite other prior research suggesting superiority of metformin, particularly for macrovascular outcomes, despite similarity in glycemic control compared to other agents.
The emerging picture is that for microvascular disease the more you lower blood sugar the better, no matter how. For macrovascular disease this does not hold true in simple fashion. If lowering blood sugar does matter, it matters how and with what.