Metformin with Extended Release in the Treatment of Prediabetes
The benefit of metformin in preventing the development of diabetes in people with prediabetes has been demonstrated in clinical studies. However, these studies evaluated immediate-release metformin, not its extended-release form (XR). Therefore, the results of an observational study conducted at Polish and Hungarian centers, which examined the efficacy and safety of metformin XR in patients with prediabetes, are important in this context. It is also necessary to add that in our country, no drug containing this active substance has yet received an approved indication for the therapy of patients with prediabetes.
Prediabetes – Definition and Treatment
Prediabetes is characterized by an increase in glycemic markers that do not yet meet the definition of diabetes. Its presence is associated with a high risk of developing type 2 diabetes and cardiovascular diseases. According to the American Diabetes Association (ADA) guidelines, prediabetes is defined as a glycated hemoglobin (HbA1c) level of 39–47 mmol/mol, fasting plasma glucose (FPG) of 5.6–6.9 mmol/l, or 2-hour plasma glucose during an oral glucose tolerance test (oGTT) of 7.8–11.1 mmol/l (i.e., impaired glucose tolerance – IGT).
Lifestyle modifications (diet, physical activity, and weight reduction) are recommended for all individuals with prediabetes. The benefit of pharmacotherapy has also been demonstrated. In the Diabetes Prevention Program (DPP) and other randomized studies, metformin reduced the risk of developing diabetes in individuals with increased FPG or IGT. However, the studies evaluated immediate-release metformin.
Observational Study With Metformin XR in Prediabetes
Hungarian and Polish authors conducted a study to evaluate the efficacy and safety of metformin XR at a dose of 1000–1500 mg once daily in adults with prediabetes. This was a prospective, open-label observational study. The primary endpoint was the proportion of patients achieving FPG < 5.6 mmol/l after 12 weeks of treatment. The main secondary endpoint was the proportion of patients with normalization of HbA1c (< 38.8 mmol/mol) after 12 weeks of treatment.
Study Population
The study included 686 individuals (at 22 centers in Poland and 9 in Hungary) with an average age of 60 years, an average body mass index (BMI) of 30.6 kg/m2, and an average duration of prediabetes of 1.2 months. Approximately 65% of the participants had concurrent hypertension, 46% had dyslipidemia, 6% had ischemic heart disease (IHD), and 3% had atrial fibrillation (AF). The diagnosis of prediabetes prompted increased physical activity in 26% and dietary changes in 40% of patients.
Treatment Efficacy
The average dose of metformin XR was 1000 mg/day. The baseline FPG was 6.2 mmol/l, which decreased by 0.55 mmol/l over the 12-week period of metformin XR treatment. Glycemic normalization was achieved in 43% of participants. Predictors of failure to normalize FPG included higher age, higher BMI, non-compliance with diet, and alcohol consumption. HbA1c levels at baseline and after 12 weeks were known for 129 patients, with normalization occurring in half of the cases during the 12 weeks of metformin XR use.
Safety Profile
Metformin was well tolerated. The most common adverse events were gastrointestinal, as expected, and all resolved. Adherence to treatment was excellent in 84% of patients and good in 7%.
Conclusion
Metformin XR normalized FPG in approximately 2/5 of individuals with prediabetes. These real-world practice results confirm the benefit of metformin in the treatment of prediabetes.
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Source: Hostalek U., Zilahi Z. Observational study of the efficacy of prolonged-release metformin in people with prediabetes. Curr Med Res Opin 2020; 36 (3): 397–401, doi: 10.1080/03007995.2019.1700360.
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