From the Guidelines
Metformin should be considered for patients with prediabetes who are at high risk for developing type 2 diabetes, particularly those with a BMI ≥35 kg/m², those under 60 years of age, or women with a history of gestational diabetes, as recommended by the most recent guidelines 1. The typical starting dose is 500 mg once daily with a meal, gradually increasing to 500 mg twice daily if tolerated, with a maximum dose of 2000 mg daily divided into two doses. Metformin works by reducing hepatic glucose production, improving insulin sensitivity, and decreasing intestinal glucose absorption. It's most effective when combined with lifestyle modifications including weight loss of 5-7% of body weight and at least 150 minutes of moderate physical activity weekly. Some key points to consider when prescribing metformin for patients with prediabetes include:
- Monitoring for vitamin B12 deficiency, as metformin may be associated with biochemical vitamin B12 deficiency 1
- Monitoring renal function, as metformin is contraindicated in those with an eGFR below 30 ml/min/1.73m²
- Common side effects include gastrointestinal symptoms like diarrhea and nausea, which can be minimized by starting with a low dose and taking the medication with food
- Regular follow-up every 3-6 months is recommended to assess effectiveness and monitor for side effects The most recent guidelines also emphasize the importance of screening for and treating modifiable risk factors for cardiovascular disease in patients with prediabetes, as they are at increased risk for cardiovascular disease events 1. Overall, metformin can be a useful addition to lifestyle modifications for patients with prediabetes who are at high risk for developing type 2 diabetes, and its use should be considered on a case-by-case basis, taking into account the individual patient's risk factors and medical history.
From the FDA Drug Label
12 CLINICAL PHARMACOLOGY
- 1 Mechanism of Action Metformin is an antihyperglycemic agent which improves glucose tolerance in patients with type 2 diabetes mellitus, lowering both basal and postprandial plasma glucose.
The FDA drug label does not answer the question.
From the Research
Treatment of Prediabetes with Metformin
- Metformin has been shown to be effective in delaying or preventing the onset of diabetes in individuals with prediabetes 2, 3, 4, 5.
- The efficacy of metformin for diabetes prevention has been proven in large, well-designed, randomized trials, such as the Diabetes Prevention Program 2.
- Metformin is generally well-tolerated and safe, with decades of clinical use demonstrating its safety profile 2.
- Metformin is most effective for women with prior gestational diabetes and for individuals younger than 60 years with a 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 3.
Comparison with Lifestyle Interventions
- Lifestyle interventions, including calorie restriction, increased physical activity, self-monitoring, and motivational support, have been shown to decrease the incidence of diabetes by 6.2 cases per 100 person-years during a 3-year period 3.
- Metformin decreased the risk of diabetes among individuals with prediabetes by 3.2 cases per 100 person-years during 3 years 3.
- Lifestyle modification is associated with a larger benefit than metformin 3.
- Intensive lifestyle intervention has also been shown to reduce all-cause mortality in a long-term follow-up study 4.
Clinical Practice and Guidelines
- Current US guidelines consider high-normal HbA1c to represent a prediabetic state 2.
- The American Diabetes Association recommends metformin as a first-line treatment for prediabetes, especially for those with a high risk of progressing to diabetes 3.
- Physicians' self-reported rates of prediabetes treatment are improving, but patterns of actual referral, prescription, and medical nutrition therapy visits are unknown 6.
- Treatment rates appear to reflect provider rather than patient preferences, with some primary care providers never treating prediabetes and others treating more than half of their patients 6.