From the Guidelines
Metformin can be used for prediabetes, particularly in adults at high risk of type 2 diabetes, as typified by the Diabetes Prevention Program, especially those aged 25–59 years with BMI ≥35 kg/m², and in individuals with prior gestational diabetes mellitus. According to the most recent guidelines from the Diabetes Care journal in 2024 1, metformin has the most safety data as a pharmacologic therapy for diabetes prevention. The recommended starting dose of metformin is typically 500 mg once daily, which can be gradually increased to 850-1000 mg twice daily as tolerated. Metformin works by reducing glucose production in the liver, improving insulin sensitivity, and decreasing intestinal absorption of glucose.
For prediabetes management, metformin is most beneficial for individuals with a BMI over 35, those under 60 years old, women with a history of gestational diabetes, or people with rising A1C levels despite lifestyle modifications. Lifestyle changes, including weight loss of 5-7% of body weight, 150 minutes of physical activity weekly, and a healthy diet, remain the first-line approach for prediabetes. Metformin should be taken with meals to minimize gastrointestinal side effects like nausea, diarrhea, and abdominal discomfort, which typically improve over time. Regular monitoring of kidney function and vitamin B12 levels is important during long-term use, as metformin may be associated with biochemical vitamin B12 deficiency 1.
Some key points to consider when using metformin for prediabetes include:
- Metformin may be cost-saving over a 10-year period compared to lifestyle modification alone 1
- Metformin was as effective as lifestyle modification in participants with BMI ≥35 kg/m² and in younger participants aged 25–44 years in the DPP 1
- Women with a history of GDM who took metformin had an equivalent 50% reduction in diabetes risk compared to those who underwent intensive lifestyle modification 1
- Metformin can reduce the risk of progression to type 2 diabetes, although the exact percentage of risk reduction may vary depending on the population and study 1
Overall, metformin can be a useful addition to lifestyle modifications for individuals with prediabetes, particularly those at high risk of progressing to type 2 diabetes. However, it is essential to weigh the benefits and risks of metformin therapy and monitor patients regularly for potential side effects and changes in kidney function and vitamin B12 levels.
From the Research
Metformin for Prediabetes
- Metformin can be used to decrease the risk of diabetes among individuals with prediabetes 2, 3, 4.
- The efficacy of metformin for delaying or preventing the onset of diabetes has been proven in large, well-designed, randomized trials, such as the Diabetes Prevention Program 3.
- Metformin is most effective for women with prior gestational diabetes and for individuals younger than 60 years with body mass index of 35 or greater, fasting plasma glucose level of 110 mg/dL or higher, or HbA1c level of 6.0% or higher 2.
- A meta-analysis found that metformin decreased the rate of conversion from prediabetes to diabetes, with a number needed to treat of between 7 and 14 for treatment over a 3-year period 4.
Benefits and Considerations
- Metformin enhances the action of insulin in liver and skeletal muscle, and its efficacy for delaying or preventing the onset of diabetes has been proven in large, well-designed, randomized trials 3.
- Decades of clinical use have demonstrated that metformin is generally well-tolerated and safe 3.
- Lifestyle interventions aimed at inducing weight loss are difficult for patients to maintain, and the weight loss achieved tends to be regained over time, making metformin a potential alternative or adjunct therapy 3.
- First-line therapy for prediabetes is lifestyle modification that includes weight loss and exercise or metformin, with lifestyle modification associated with a larger benefit than metformin 2.