Metformin or lifestyle interventions in prediabetic patients could not reduce the risk of an adverse CV outcome compared to placebo.
Metformin use or lifestyle interventions could not reduce the risk of an adverse cardiovascular event (CV) in patients with prediabetes. This was the key finding of a 21-year follow-up study by the Diabetes Prevention Program Research Group.
A 2018 global review of cardiovascular disease (CVD) in patients with type 2 diabetes found a prevalence of 32.2% and noted that CVD mortality accounts for approximately half of all deaths in these patients. In 1998, the results of a prospective study of diabetes in the United Kingdom showed that metformin use reduced all-cause mortality by 36%. In addition, a study of the long-term effects of lifestyle interventions on people with impaired glucose tolerance found that these interventions delayed the onset of type 2 diabetes, as well as reducing the incidence of cardiovascular mortality. and for all causes. With a potential cardiovascular and mortality benefit from both metformin and lifestyle interventions aimed at reducing weight and increasing physical activity, the Diabetes Prevention Program Research Group examined the value of each intervention in a randomized trial, the Diabetes Prevention Program (DPP) study that was published in 2002. The study assigned 3,234 non-diabetic participants with high plasma glucose concentrations on an empty stomach and after loading. placebo, metformin (850 mg twice daily) or a lifestyle modification program. The results showed that both metformin and lifestyle interventions reduced the incidence of diabetes in high-risk individuals by 58 and 31%, respectively, for an average of 2.8 years.
Based on these findings, the researchers invited pre-diabetic participants from the original DPP to enroll in a follow-up study to determine whether metformin and lifestyle interventions could reduce the incidence of adverse cardiovascular outcomes. Participants continued with the same dose of metformin (850 mg twice daily) and lifestyle intervention. The primary outcome was the first occurrence of a major cardiovascular event that was previously specified as non-fatal myocardial infarction, non-fatal stroke, or fatal CVD.
Metformin or CVD lifestyle interventions and outcomes
A total of 3234 individuals with a mean initial age of 51 years (68% women) and a mean fasting blood insulin level of 160 pmol / L were followed for an average of 21 years and of which, 1073 were assigned to placebo, 1082 metformin, and 1079 a lifestyle intervention.
During the follow-up period, 310 people experienced an adverse cardiovascular event; 101 for patients assigned to metformin and 111 for lifestyle intervention. These events did not differ significantly from placebo (risk ratio, HR = 1.03, 95% CI 0.78 – 1.37, p = 0.81, metformin vs. placebo) and a risk ratio ‘1.14 (95% CI 0.87 – 1.40, p = 0.34) for lifestyle vs placebo. When non-fatal myocardial infarctions and strokes are considered separately, there are no significant differences for any intervention compared to placebo.
The authors concluded that, despite the value of each intervention to reduce the risk of developing type 2 diabetes, none was associated with a reduced risk of cardiovascular events in prediabetic patients.
Goldberg RB et al. Effects of Long-Term Metformin and Lifestyle Interventions on Cardiovascular Events in the Diabetes Prevention Program and Its Outcome 2022