No CV benefit with metformin, lifestyle intervention, despite diabetes prevention
Click Here to Manage Email Alerts
In adults with prediabetes, metformin and lifestyle interventions decreased the likelihood of type 2 diabetes development but did not reduce risk for major adverse CV events compared with placebo during 21 years of follow-up, data show.
In a review of long-term follow-up data from the Diabetes Prevention Program Outcomes Study (DPPOS), researchers also noted that the findings should be viewed in the context of several other factors, including a modest progression of hyperglycemia, extensive out-of-study use of lipid-lowering and antihypertensive medications and increased out-of-study metformin use over time.
“Effective control of major cardiovascular risk factors in cohorts with diabetes has been shown to reduce the risk of CVD,” Ronald B. Goldberg, MD, professor of medicine, biochemistry and molecular biology in the division of endocrinology, diabetes and metabolism at the University of Miami Miller School of Medicine and senior faculty member of the Diabetes Research Institute, and colleagues wrote. “This was therefore a relatively low-risk cohort from the standpoint of the prevention of CVD. It is thus possible that the accelerating effect of the duration of clinically diagnosed diabetes on cardiovascular risk has still not had enough time to manifest, making it more difficult to identify a beneficial effect of metformin.”
Goldberg and colleagues analyzed data from 3,234 participants with impaired glucose tolerance randomly assigned to metformin 850 mg twice daily, intensive lifestyle or placebo, and followed for 3 years during the initial Diabetes Prevention Program (DPP) study. The mean baseline age of participants was 51 years, 68% were women and 54.7% were white. During the next 18 years of follow-up in DPPOS, all participants were offered a less intensive group lifestyle intervention; unmasked metformin was continued in the metformin group. The primary outcome was the first occurrence of nonfatal MI, stroke or CV death; an extended CV outcome included the primary outcome or hospitalization for HF or unstable angina, coronary or peripheral revascularization, CHD or silent MI by ECG. Researchers assessed ECGs and CV risk factors annually.
During follow-up, 310 participants experienced a first major CV event; incidence did not differ by treatment group.
Researchers found that neither metformin nor lifestyle intervention reduced the primary outcome. Compared with placebo, the HR for metformin was 1.03 (95% CI, 0.78-1.37; P = .81) and the HR for lifestyle was 1.14 (95% CI, 0.87-1.5; P = .34). Results persisted after adjustment for risk factors and results were similar when researchers assessed the extended CV outcome.
“Although it is reassuring that metformin was not associated with any overall unfavorable effects on CVD, it is surprising that neither intervention yielded benefit for CVD through their effect on diabetes prevention,” the researchers wrote. “It may be that a beneficial effect related to diabetes prevention was not apparent in our study because the development of diabetes in its very early stages may not, per se, have increased cardiovascular risk above the effect of known risk factors.”
Collapse
Click Here to Manage Email Alerts