From the Guidelines
Metformin prophylaxis reduces the risk of developing type 2 diabetes by approximately 31% in individuals with prediabetes, as evidenced by the most recent and highest quality study 1. The standard regimen typically starts with metformin 500 mg once daily with a meal, gradually increasing to 850-1000 mg twice daily as tolerated to minimize gastrointestinal side effects. This preventive approach is most effective in people under 60 years of age, those with a BMI ≥35 kg/m², and women with a history of gestational diabetes. Some key points to consider when using metformin for diabetes prevention include:
- Metformin has the most safety data as a pharmacologic therapy for diabetes prevention 1
- Metformin was overall less effective than lifestyle modification in the DPP, though group differences attenuated over time in the DPPOS 1
- Metformin may be cost-saving over a 10-year period 1
- In the DPP, metformin was as effective as lifestyle modification in participants with BMI ≥35 kg/m² and in younger participants aged 25–44 years 1
- In individuals with a history of GDM in the DPP, metformin and intensive lifestyle modification led to an equivalent 50% reduction in diabetes risk 1 For optimal results, metformin should be combined with lifestyle modifications including dietary changes and increased physical activity, which together can reduce diabetes risk by up to 58% 1. Metformin works by decreasing hepatic glucose production, improving insulin sensitivity, and reducing intestinal glucose absorption. Common side effects include diarrhea, nausea, and abdominal discomfort, which typically improve over time. Regular monitoring of kidney function is necessary, and vitamin B12 levels should be checked periodically as metformin can decrease absorption 1. This preventive therapy is most appropriate for high-risk individuals who have failed to achieve adequate results with lifestyle modifications alone. Some of the benefits of metformin include:
- Reduction in diabetes risk by up to 31% 1
- Cost-saving over a 10-year period 1
- Equivalent reduction in diabetes risk to lifestyle modification in certain subgroups, such as those with BMI ≥35 kg/m² and women with a history of GDM 1 However, it is essential to weigh these benefits against the potential risks and side effects, and to carefully consider the individual patient's needs and circumstances before initiating metformin therapy.
From the Research
Rate of Prevention of Diabetes with Metformin Prophylaxis for Prediabetes
- The Diabetes Prevention Program/Diabetes Prevention Program Outcomes Study (DPP/DPPOS) found that metformin reduced the incidence of diabetes by 31% compared with placebo after an average follow-up of 2.8 years 2.
- The DPP/DPPOS also showed a risk reduction of 18% over 10 and 15 years post-randomisation 2.
- A study published in Diabetes Spectrum found that metformin therapy reduced progression to diabetes by 31% compared to placebo in people at risk of type 2 diabetes 3.
- A review of metformin use for type 2 diabetes prevention found that metformin was associated with reduced relative risk of incident diabetes, with the strongest evidence for use in those at highest risk 4.
- The Diabetes Prevention Program and its follow-up, the Diabetes Prevention Program Outcomes Study, found that metformin reduced the incidence of diabetes by 17% or 36% based on glucose or HbA1c levels, respectively, over 15 years of follow-up 5.
- A narrative review found that metformin reduced the 3-year risk of diabetes by 31% in the randomized phase of the Diabetes Prevention Program, and that diminishing but still significant reductions in diabetes risk were present in the trial's epidemiological follow-up at 10,15, and 22 years 6.
Subgroups that Benefited Most from Metformin
- Women with a history of prior gestational diabetes mellitus (GDM) had a greater effect from metformin, with a hazard ratio (HR) of 0.59 and a rate difference (RD) of -4.57 cases/100 person-years 5.
- Metformin had greater effects at higher baseline fasting glucose levels, with a HR of 0.94 and a RD of -0.38 cases/100 person-years for parous women without GDM, compared to a HR of 0.59 and a RD of -4.57 cases/100 person-years for women with GDM 5.
- Metformin was more effective in subjects with higher baseline HbA1c, with a RD of -1.03 cases/100 person-years with baseline HbA1c <6.0% (42 mmol/mol) and -3.88 cases/100 person-years with 6.0-6.4% (P = 0.0001) 5.