Effects of Metformin Versus Glipizide on Cardiovascular Outcomes in Patients With Type 2 Diabetes and Coronary Artery Disease

Abstract

OBJECTIVEThe two major classes of antidiabetic drugs, sulfonylureas and metformin, may differentially affect macrovascular complications and mortality in diabetic patients. We compared the long-term effects of glipizide and metformin on the major cardiovascular events in type 2 diabetic patients who had a history of coronary artery disease (CAD).RESEARCH DESIGN AND METHODSThis study is a multicenter, randomized, double-blind, placebo-controlled clinical trial. A total of 304 type 2 diabetic patients with CAD, mean age = 63.3 years (range, 36–80 years), were enrolled. Participants were randomly assigned to receive either glipizide (30 mg daily) or metformin (1.5 g daily) for 3 years. The primary end points were times to the composite of recurrent cardiovascular events, including death from a cardiovascular cause, death from any cause, nonfatal myocardial infarction, nonfatal stroke, or arterial revascularization.RESULTSAt the end of study drug administration, both groups achieved a significant decrease in the level of glycated hemoglobin (7.1% in the glipizide group and 7.0% in the metformin group). At a median follow-up of 5.0 years, 91 participants had developed 103 primary end points. Intention-to-treat analysis showed an adjusted hazard ratio (HR) of 0.54 (95% CI 0.30–0.90; P = 0.026) for the composites of cardiovascular events among the patients that received metformin, compared with glipizide. The secondary end points and adverse events were not significantly different between the two groups.CONCLUSIONSTreatment with metformin for 3 years substantially reduced major cardiovascular events in a median follow-up of 5.0 years compared with glipizide. Our results indicated a potential benefit of metformin therapy on cardiovascular outcomes in high-risk patients.

Metformin, but Not Rosiglitazone, Attenuates the Increasing Plasma Levels of a New Cardiovascular Marker, Fibulin-1, in Patients With Type 2 Diabetes

“…However, it has also been suggested that the effect of metformin is at least partly independent of its blood glucose-lowering effect (9). This idea is compatible with a recent study that found beneficial effects on cardiovascular outcome in T2D patients with coronary artery disease on metformin compared with glipizide, despite similar effects on HbA 1c (10). The mechanisms by which metformin exerts such putative beneficial cardiovascular effects are unclear but have been suggested to include an ability to reduce inflammatory and coagulative activities and to reduce the expression of vascular adhesion molecules as well as improve endothelial function and fibrinolysis (11)(12)(13)(14)(15).…”

The Current Role of Glucose Control Medications in Primary and Secondary Prevention for Cardiovascular Disease

“…At a median follow-up of 5 years, both groups achieved goal HbA1c levels (7.1% vs. 7.0%) but metformin was associated with a 12% absolute risk reduction in the composite primary outcome of nonfatal MI, nonfatal stroke, revascularization, CV mortality, or all-cause mortality. 10 Recent trials using newer therapies like dipeptidyl peptidase-4 demonstrated non inferiority (safety) in cardiovascular outcomes among patients with T2DM and existing CVD or at higher risk of events. [11][12][13][14] Recently, for example, the use of sitagliptin in more than 7.000 patients -in the TECOS trial -was not associated with an increased risk of heart failure or related adverse outcomes after Sitagliptin therapy.11 There was, however, an increase in the rate of hospitalization for HF with the use of saxagliptin (SAVOR-TIMI 53) trial.…”

Metformin in advanced chronic kidney disease: are current guidelines overly restrictive?

“…In a trial of 304 people with type 2 diabetes and coronary artery disease, metformin monotherapy significantly reduced composite cardiovascular events in comparison to glipizide over five years of follow-up (HR 0.54, 95% CI 0.30 to 0.90). 35 Furthermore, Roussel et al examined data from 19,691 participants with diabetes and established atherothrombosis in the Reduction of Atherothrombosis for Continued Health (REACH) registry. 36 They found that mortality was lower for patients with an eGFR ≥30 mL/min who had been prescribed metformin compared with those who were not.…”