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Diabetes currently affects an estimated 171 million individuals worldwide.1 In the United States, diabetes is the fifth leading cause of death and was responsible for an estimated $132 billion in direct and indirect costs in 2002.2 With a doubling of the cases of diabetes worldwide expected by 2030, there is an urgent need to discover effective prevention strategies.1
The US Department of Health and Human Services and the American Diabetes Association (ADA) now use the term "prediabetes" to describe an increasingly common condition in which blood glucose levels are higher than normal but do not indicate diabetes as reflected by impaired glucose tolerance (IGT) or impaired fasting glucose. Studies have shown that people with prediabetes are likely to develop type 2 diabetes within 10 years unless they make changes in their diet and level of physical activity.3
Does Early Pharmacotherapy Make a Difference?
Several oral hypoglycemic agents have been studied for the primary prevention of type 2 diabetes, with varying results. Pharmacologic therapy may offer a prevention option for patients who either are unsuccessful with lifestyle interventions or are unable to undertake the rigors of diet and exercise.
The largest trial of a pharmacotherapeutic agent was the Diabetes Prevention Program, which randomized 3234 patients with elevated fasting and postload plasma glucose to treatment placebo, metformin 850 mg twice daily, or intensive lifestyle intervention.4 After a mean follow-up period of 2.8 years, the incidence of diabetes was reduced by 58% with lifestyle intervention and by 31% with metformin use, as compared with placebo. Metformin was most effective in younger age groups and in patients who were significantly overweight. It was ineffective in patients >60 years of age. Other studies using biguanides found no significant reduction in the incidence of diabetes, compared with placebo, but these studies had low diabetes incidence rates and were likely underpowered to show significant benefit.5,6
Acarbose was studied as a preventive agent in the Study to Prevent Non-insulin Dependent Diabetes Mellitus (STOPNIDDM) trial. This study showed a relative risk reduction for the development of diabetes in the acarbose group after the 39-month study period. Yet, 25% of the study population discontinued therapy early, largely because of acarbose-induced gastrointestinal toxicity.7
Two studies examined the effect of tolbutamide therapy on the incidence of diabetes in patients with IGT or high-normal to elevated fasting glucose levels.8,9 Neither study reported a statistically significant decrease in the incidence of type 2 diabetes. Both studies were small and potentially underpowered, however. Glimepiride and gliclazide currently are under study for primary prevention.
The Troglitazone Prevention of Diabetes (TRIPOD) study showed a decrease in diabetes incidence from 45% to 20% in high-risk Hispanic women using troglitazone.10 It is difficult to draw conclusions based on this study, however, because investigators were able to assess incidence of diabetes during the follow-up period in only approximately one half of eligible patients. Rosiglitazone with or without ramipril is currently under investigation as a preventive regimen.
Although decreases in the incidence of diabetes were seen in some prevention studies, the data are far from clearly supporting the use of any of the studied drugs as preventive agents. The ADA has issued a position paper on the use of pharmacologic therapy for diabetes prevention.11 Based on the available evidence, it concludes that "there is insufficient evidence to support the use of drug therapy as a substitute for, or routinely used in addition to, lifestyle modification to prevent diabetes. Until there are studies showing that drugs will delay or prevent the complications of diabetes, or until the cost-effectiveness of using pharmacological agents has been established, we do not recommend the routine use of these agents to prevent diabetes."
Patients who are prediabetic need to be aware of the significant benefits of lifestyle modification. Current recommendations include decreasing body weight by at least 5%, limiting fat intake to 30% of calories, limiting saturated fat intake to <10% of calories, increasing fiber to at least 15 g/1000 calories, and exercising at least 150 minutes/week. Meeting these goals can reduce the incidence of progression to diabetes by 58%.4
Dr. Garrett is a clinical pharmacist practitioner at Cornerstone Health Care in High Point, NC.
For a list of references, send a stamped, self-addressed envelope to: References Department, Attn. A. Rybovic, Pharmacy Times, Ascend Media Healthcare, 103 College Road East, Princeton, NJ 08540; or send an email request to: firstname.lastname@example.org