Diabetes Mellitus: Present and Future Preventive Strategies—Part II

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Citation:

Pages 30 - 35

Authors:

Paul Aoun, DO, PhD, Charles R. Albrecht III, MD, and Steven R. Gambert, MD

Prevention of type 2 diabetes mellitus at a preclinical phase with pharmacologic treatment has been gaining interest. Medications that have been proposed include acarbose, metformin, orlistat, antihypertensives, and the thiazolidinediones (TZDs). The pharmacologic prevention of complications of diabetes using pharmacologic means, or tertiary prevention, is beyond the scope of this discussion. The Study TO Prevent Non–Insulin-Dependent Diabetes Mellitus (STOP-NIDDM) is a double-blind, placebo-controlled, randomized trial with an intention-to-treat analysis evaluating high-risk persons with impaired glucose tolerance. The participants received either a placebo or acarbose 100 mg 3 times daily, an alpha-glucosidase inhibitor known to improve sensitivity to insulin and decrease postprandial hyperglycemia. Both groups also received instruction on weight reduction and exercise, and had a yearly meeting with a dietician. A total of 714 patients were allocated to the treatment arm, and 715 received placebo. The mean follow-up time was 3.3 years, and the primary endpoint was development of diabetes. Nearly one-quarter of patients randomized to acarbose discontinued treatment because of gastrointestinal side effects including flatulence, diarrhea, and abdominal cramping. Of the patients who completed the study, there was a 25% reduction in the risk of progression to type 2 diabetes for those who already had developed impaired glucose tolerance. Of note, the incidence of diabetes actually increased following the discontinuation of acarbose taken as part of this study.1 Correspondence that followed questioned whether the positive results merely reflected a delay in the progression of diabetes rather than an actual prevention.2 Metformin, a biguanide, is known to increase muscle tissue insulin sensitivity and decrease hepatic glucose production. Several studies have been published regarding the potential use of metformin to prevent type 2 diabetes mellitus, with the initial studies being limited by small samples and lack of data regarding adherence. A large, double-blind, randomized, controlled trial of 3234 patients with an intention-to-treat analysis compared the effectiveness of metformin, placebo, or “intensive” lifestyle modification in preventing the primary outcome of progression to diabetes based on 1997 American Diabetes Association (ADA) criteria. The mean follow-up period was 2.8 years, mean age 50.6 years, mean body mass index (BMI) 34, and mean HbA1c 5.91. As compared to placebo, metformin and intensive lifestyle modification reduced the incidence of diabetes by 31% and 58%, respectively. Metformin was less effective in patients with a lower baseline BMI and lower baseline fasting blood glucose, and was associated with an increased incidence of gastrointestinal adverse effects. The researchers concluded that both metformin and intensive lifestyle modification prevented or delayed progression to frank diabetes, with effects being similar across groups regardless of gender, race, ethnicity, or age.3 A recent review summarized the results of clinical trials thus far in answering the question of whether metformin prevented type 2 diabetes mellitus. The authors concluded that given the lack of long-term data and possibility of “masking disease” rather than “preventing disease,” more studies are required before practice changes are made.4 Recent research into cost-effectiveness has shown that the cost per quality adjusted life-year from a societal perspective was $8800 for the lifestyle intervention and $29,900 for the metformin intervention.

References:

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