London, UK - The alpha-glucosidase inhibitor acarbose delays the development of type 2 diabetes in patients with impaired glucose tolerance (IGT) and could be used, either as an alternative or in addition to lifestyle changes, to ward off the disease in this vulnerable population, according to a study in the June 15, 2002 issue of the Lancet.
People who develop type 2 diabetes first pass through a phase of impaired glucose tolerance, which is characterized by postprandial hyperglycemia and increased insulin resistance. An intervention during this prediabetic state to reduce resistance to insulin could avert this progression, Dr Jean-Louis Chiasson (Centre Hospitalier de L'Université de Montréal, Hôtel-Dieu, Montreal, Canada) and other investigators for the Study To Prevent Non-Insulin-Dependent Diabetes Mellitus (STOP-NIDDM) trial reasoned. Chiasson et al recruited patients with a BMI of between 25 and 40 kg/m2 at high risk for developing type 2 diabetes, particularly those who had first-degree relatives with the disease. Patients with IGT, defined as a 2-h plasma glucose concentration of >7.8 mmol/L and <11.1 mmol/L after a 75-g glucose load and a fasting plasma glucose concentration of 5.6 to 7.7 mmol/L, a value associated with a 3- to 4-fold increase in risk of progression to diabetes, were deemed eligible for the study.
Patients were randomized to acarbose 3 times a day (n=682) or to placebo (n=686). To keep the known gastrointestinal side effects of acarbose (ie flatulence, diarrhea, abdominal cramps) to a minimum, the drug was started at 50 mg per day and increased gradually to a maximum of 100 mg 3 times per day or to the maximum tolerated dose. Patients were also encouraged to exercise regularly and to follow a weight-reduction or weight-maintenance diet. They all met with a dietician before randomization and once a year thereafter and kept a nutritional and physical activity diary for the 3 days that preceded their yearly visits.
In addition, patients were seen once every 3 months by a nurse, who recorded adverse events, pill counts, and fasting blood sugar levels, and were examined once every 6 months by an investigator. The mean duration of follow-up was 3.3 years, and the primary end point of the trial was development of diabetes, defined as a plasma glucose concentration of >11.1 mmol/L 2 hours after a 75-g glucose load, Chiasson et al note.
Acarbose probably prevents the development of diabetes by decreasing the postprandial rise in blood glucose
Of the 682 patients randomized to acarbose, 221 (32%) developed diabetes, and of the 686 who received placebo, 285 (42%) developed diabetes (relative hazard 0.75 [95% CI 0.63-0.90]; p=0.0015). As well, patients on acarbose were more likely to have their impaired glucose tolerance revert back to normal glucose tolerance than patients on placebo, the investigators report.
They add that acarbose probably prevents the development of diabetes by decreasing the postprandial rise in blood glucose. This effect "could decrease toxic effects of glucose and thus delay conversion of impaired glucose tolerance to diabetes. It could also possibly explain, at least in part, why acarbose treatment was associated with an increased reversion to normal glucose tolerance," Chiasson et al write.
In an interview with heartwire , Chiasson expanded on these views. "Most of the major epidemiological studies have shown that postprandial hyperglycemia is the best predictor of cardiovascular disease, because it increases oxidative stress. Acarbose cuts down on this hyperglycemia. This may be one of the mechanisms involved in the prevention of diabetes and, it is hoped, in the prevention of cardiovascular disease," he said.
Heartwire from Medscape © 2002
Cite this: Acarbose staves off type 2 diabetes - Medscape - Jun 13, 2002.