The prevalence of type 2 diabetes mellitus is expected to double over the next 25 years, making efforts to delay the onset of this condition a worldwide public health priority. Because resistance to insulin progressively increases during the transition from impaired glucose tolerance to overt diabetes, interventions to improve sensitivity to glucose should delay onset of diabetes. Chiasson and colleagues studied the efficacy of the alpha-glucosidase inhibitor acarbose in preventing or delaying conversion of impaired glucose tolerance to type 2 diabetes.

The double-blind, placebo-controlled, randomized trial recruited 1,429 men and women aged 40 to 70 years from seven European countries, Israel, and Canada who were at high risk for developing diabetes. Patients were required to have a body-mass index (BMI) of between 25 to 40 kg per m², a fasting plasma glucose concentration of 100.9 to 138.7 mg per dL (5.6 to 7.7 mmol per L), and impaired glucose tolerance (defined as a plasma glucose level of 140.5 to 200 mg per dL [7.8 to 11.1 mmol per L] after a 75-g glucose load). Most participants were first-degree relatives of persons with type 2 diabetes. Participants were randomly allocated to take 100 mg of acarbose or an identical placebo three times daily with meals. To minimize side effects, the initial dosage of 50 mg per day was increased gradually.

All patients received nutritional counseling for weight reduction and were encouraged to exercise regularly. Nurses reviewed medication compliance, side effects, and blood glucose levels every three months, and a physician examined patients every six months for at least three years. The primary end point was development of diabetes, which was defined as a plasma glucose level of at least 200 mg per dL two hours after a 75-g glucose load.

Results were available for 682 of the 714 patients randomized to acarbose and 686 of the 715 allocated to placebo. The patients were comparable in all important respects at the beginning of the study. Thirty percent of the acarbose group and 18 percent of the placebo group discontinued the study. The most common reason was gastrointestinal side effects, and these were significantly more common in patients taking acarbose.

Diabetes developed in 221 patients (32 percent) taking acarbose, compared with 285 patients (42 percent) in the control group. This significant difference represented a 25 percent reduction in risk. The difference remained significant even after adjusting for weight change and was consistent irrespective of age, sex, and original BMI. Treatment with acarbose also was associated with improved glucose tolerance in patients who reverted to normal glucose tolerance.

The authors conclude that acarbose reduced the risk of progression to diabetes by 25 percent in a high-risk group and could increase the probability of achieving normal glucose tolerance over time. These changes were independent of age, sex, or BMI and appeared to be synergistic with other strategies, particularly weight loss. The authors calculate that 11 patients need to be treated for 3.3 years to prevent one case of diabetes. Other than the gastrointestinal symptoms, acarbose had no serious side effects. The authors call for acarbose to be used either alone or in combination with lifestyle modifications to delay the onset of diabetes in patients with impaired glucose tolerance.

editor's note: This study offers great hope in the struggle to prevent type 2 diabetes, but achieving the full potential of acarbose therapy will require skillful family doctoring. Far from being as easy as taking a pill three times daily, this therapy was associated with gastrointestinal symptoms in 83 percent of patients. Significant skill will be required to assist patients to persevere. Patients with impaired glucose tolerance have many symptoms (60 percent of the placebo group also reported gastrointestinal symptoms, and other symptoms were reported by 95 percent of patients in that group), and patients could attribute them to the medication, leading to poor adherence. Furthermore, it seems likely that the greatest success comes when acarbose is combined with lifestyle changes. If this therapy becomes widely used, it must be taken seriously and not become another failure for patients who often seem trapped in cycles of promising initiatives that eventually are abandoned or perceived to be unsuccessful.—a.d.w.