Metformin fails to prevent diabetes in non-diabetic cardiovascular patients: Systematic review and meta-analysis

Abstract

BACKGROUND

Metformin, a first-line therapy for type 2 diabetes mellitus (T2DM), has demonstrated potential preventive effects in high-risk individuals, especially in those with prediabetes. However, its role in preventing diabetes specifically among non-diabetic patients with established cardiovascular disease (CVD) remains unclear. Given the clinical and public health importance of diabetes prevention in this high-risk group, a systematic evaluation of existing evidence from randomized controlled trials is necessary to inform treatment strategies.

AIM

To investigate the effectiveness of metformin in preventing T2DM among patients with CVD who do not have diabetes.

METHODS

We searched PubMed, the Cochrane Central Register of Controlled Trials, and Scopus (from January 1, 2000 to July 31, 2024) for eligible randomized controlled trials (RCTs). A meta-analysis was conducted to evaluate the effect of metformin on the prevention of T2DM in patients with CVD and or coronary artery disease (CAD) without diabetes.

RESULTS

A total of 933 patients with CVD, all of whom had CAD, were included (470 in the metformin group and 463 in the control group). Fifty-six participants (11.9%) in the intervention groups and fifty-seven (12.3%) in the control groups developed T2DM. Patients with CAD receiving metformin showed no statistically significant difference in the development of T2DM compared with those not receiving metformin (odds ratio: 0.97; 95% confidence interval: 0.65-1.45; P = 0.89). Heterogeneity was rather low (Q = 2.38, P = 0.50; I² = 0%, 95% confidence interval: 0%-84%), showing satisfactory results across studies; however, the overall quality of evidence was very low. The results remained non-significant in subgroup analyses restricted to: (1) Studies conducted in similar countries; (2) Studies with or without post-intervention follow-up; (3) Studies with a predominance of male or female participants; (4) Studies with a mean participant age above or below 60 years; (5) Studies including central adiposity as an additional diabetes risk factor or not; (6) Studies including prediabetes and/or hypertension as additional risk factors or not; (7) Studies using different daily metformin dosages; and (8) Studies with different intervention durations.

CONCLUSION

The administration of metformin does not appear to be effective in preventing the development of T2DM in non-diabetic patients with CAD. However, this finding is based on a limited number of small RCTs. Therefore, results should be interpreted cautiously, and further high-quality studies are needed before definitive clinical recommendations can be made.

Keywords: Metformin; Cardiovascular disease; Coronary artery disease; New onset type 2 diabetes mellitus; Diabetes prevention; Glucagon-like-peptide-1 receptor agonists; Sodium-glucose cotransporter 2 inhibitors; Randomized controlled trials

Core Tip: This meta-analysis evaluated the role of metformin in preventing type 2 diabetes among non-diabetic patients with coronary artery disease. Across 933 participants from randomized controlled trials, metformin did not significantly reduce the incidence of diabetes compared to control. The findings were consistent across multiple subgroup analyses, including variations in age, gender, comorbidities, dosage, and follow-up duration. Despite low heterogeneity, the overall quality of evidence was very low, limiting the strength of conclusions. These results suggest that metformin should not be routinely used for diabetes prevention in non-diabetic coronary artery disease patients until more robust evidence from larger trials becomes available.