Metformin use in pre-diabetics and a BMI greater than 35 reduced the incidence of cardiovascular disease over the next three years
Metformin use in those with pre-diabetes and a body mass index (BMI) greater than 35 led to a lower incidence of cardiovascular disease over the next three years. This was the finding of a study presented at the American Heart Association Scientific Sessions 2021.
Metformin is approved both in the US and Europe for use along with diet and exercise as a means of lowering blood glucose levels in patients with type 2 diabetes. Moreover, the drug has been shown to reduce the rate of conversion from prediabetes to diabetes, an effect seen in a 2002 trial with over 3000 non-diabetic patients and elevated fasting and post loading glucose concentrations.
This finding has led to an increased ‘off-label’ use of the drug in patients with pre-diabetes, despite a recent article in 2020 cautioning against such use for the treatment of pre-diabetic patients for at least three reasons. Firstly, treatment is unnecessary because around two-thirds of pre-diabetics do not go on to develop diabetes. Secondly, a third of patients can revert to normal glucose levels and finally, patients with pre-diabetes are not at risk for the microvascular complications of diabetes, thus metformin has no impact on this important outcome. However, this is in sharp contrast to other work that has found how the presence of pre-diabetes is associated with an increased risk of cardiovascular disease. The American Diabetes Association (ADA) does suggest that metformin can be considered in pre-diabetic patients with additional risk factors such as a BMI ≥35, if they are age less than 60 years, or have history of gestational diabetes. The ADA also advocates use of the drug in those with a rising haemoglobin A1c despite the use of lifestyle interventions.
For the present study, the researchers turned to a health insurance claims database to examine the extent to which pre-diabetic patients, with or without metformin, developed cardiovascular disease (CVD). For the purposes of their analysis, pre-diabetes was defined by a HbA1c of 5.7-6.4, a fasting glucose 100-125 mg/dL or an oral glucose tolerance test result of 140-199 mg/dL, which is the usual definition of pre-diabetes. Excluded patients were those under 25 years of age and with FDA-approved metformin indications including type 1 diabetes, cardiovascular disease, chronic kidney disease or gestational diabetes.
Analysis of the database identified 149,654 patients with prediabetes, of whom 8,624 (5.8%) were prescribed metformin with an average age of 65.9 years (57.3% female). The average BMI among those prescribed metformin was 33.1 which was significantly different to the non-metformin pre-diabetic group (p < 0.001). In addition, the metformin group had a statistically higher incidence of hypertension (78% vs 61%, p < 0.001) and dyslipidaemia (60% vs 48%, p < 0.001).
After a follow-up period of 2.8 years, 24% of the pre-diabetic cohort developed CVD. When dichotomising results by BMI, among the metformin cohort with a BMI > 35, a lower proportion developed CVD compared to those with a BMI < 35 (21.2% vs 28%, p < 0.001). A similar significant result was observed for gender and BMI, with a lower incidence of CVD among those with a BMI > 35. However, while the proportion of metformin patients under 65 years of age who developed CVD was numerically lower for those with a BMI > 35 (11.3% vs 12.6%), the difference was not statistically significant (p = 0.428).
The authors concluded that among in patients with a BMI > 35, using metformin resulted in a lower proportion of developing CVD over the following three years and that these data supported the recommendations outlined by the ADA.