From the Guidelines
Metformin should be considered for prediabetic patients, particularly those at high risk for developing type 2 diabetes, as evidenced by the most recent study in 2024 1. The typical starting dose is 500 mg once daily with a meal, gradually increasing to 500-1000 mg twice daily as tolerated. Metformin is most appropriate for prediabetic individuals who have a BMI ≥35 kg/m², are under 60 years old, have a history of gestational diabetes, or have a rising A1C despite lifestyle interventions. Before starting metformin, patients should first attempt lifestyle modifications including weight loss of 5-7% of body weight, 150 minutes of physical activity weekly, and dietary changes. Some key points to consider when prescribing metformin for prediabetes include:
- Metformin works by decreasing hepatic glucose production, increasing peripheral glucose uptake, and improving insulin sensitivity.
- Common side effects include gastrointestinal symptoms like diarrhea and nausea, which can be minimized by starting with a low dose and taking it with food.
- Metformin is contraindicated in patients with significant renal impairment (eGFR <30 mL/min), severe liver disease, or conditions predisposing to lactic acidosis.
- Long-term use of metformin may be associated with biochemical vitamin B12 deficiency; consider periodic measurement of vitamin B12 levels in metformin-treated patients, especially in those with anemia or peripheral neuropathy 1. It's also important to note that people with prediabetes often have other cardiovascular risk factors, including hypertension and dyslipidemia, and are at increased risk for cardiovascular disease; therefore, screening for and treatment of modifiable risk factors for cardiovascular disease are suggested 1.
From the Research
Initiation of Metformin in Prediabetes
- Metformin is considered the drug of choice when medical treatment is warranted for patients with prediabetes 2.
- The use of metformin in patients with prediabetes has been shown to be effective in delaying or preventing the onset of type 2 diabetes 3, 4, 5, 6.
- Studies have demonstrated that 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.
- Metformin is generally well-tolerated and safe, with decades of clinical use demonstrating its safety profile 3, 4.
- The evidence suggests that metformin should be considered as initial therapy for patients with prediabetes who are unable to comply with lifestyle modification or where lifestyle modification has been ineffective in decreasing progression to type 2 diabetes 4.
Benefits of Metformin in Prediabetes
- Metformin has been associated with reduced relative risk of incident diabetes, with the strongest evidence for use in those at highest risk (i.e., aged <60 years, BMI ≥35, and women with histories of gestational diabetes) 5.
- Metformin has been deemed cost-effective in preventing type 2 diabetes in high-risk individuals 5.
- The number needed to treat with metformin to prevent one case of diabetes over a 3-year period is between 7 and 14 6.
Considerations for Metformin Use
- Despite the evidence supporting the use of metformin in prediabetes, recent studies have highlighted low rates of metformin use for diabetes prevention in real-world settings 5.
- Enhancing the translation of evidence to real-world practice has important implications for patients, providers, and payers 5.