ABSTRACT
BACKGROUND: Many new oral medications have been developed to treat diabetes, but uncertainty remains regarding which are best for initial treatment and whether effectiveness rates differ. This review compares the available oral antihyperglycemics.
POPULATION STUDIED: A total of 63 randomized controlled clinical trials involving oral hypoglycemic drugs for type 2 diabetes was identified by a MED-LINE search and review of the bibliographies of articles found initially. Other inclusion criteria were study duration of at least 3 months, at least 10 subjects at the study’s conclusion, and hemoglobin A1C levels reported. Other search details, such as the year and key words of a study, were not mentioned. More than 15,000 subjects have been enrolled in the identified trials, but no information was given regarding important clinical characteristics such as age, ethnicity, body mass index, or medical conditions other than diabetes. Therefore, assessing generalizability of the data to typical patients of family practitioners is difficult.
STUDY DESIGN AND VALIDITY: The article lists available randomized clinical trials that evaluate sulfonylureas, metformin, α-glucosidase inhibitors (AGIs), thiazolidinediones (TZDs), and nonsulfonylurea secretagogues as monotherapy versus placebo, in head-to-head trials or in combination, and compares their outcomes in terms of hemoglobin A1C reduction. When multiple doses of a drug were tested, the results from the highest dose were used. There was no attempt to synthesize the data provided by the studies into a meta-analysis.
OUTCOMES MEASURED: The major outcome measured was percent hemoglobin A1C reduction. Side effects were mentioned but not quantified. Cost, patient satisfaction, and quality of life were not addressed.
RESULTS: Except for the UKPDS, all available studies of oral hypoglycemics are short term and are limited in focus to hemoglobin A1C. Each class of drugs achieved a similar initial reduction in hemoglobin A1C of 1% to 2% except for the AGIs and nateglinide, which were less effective. The results are remarkably consistent across studies. Head-to-head comparison of specific medications further supports this conclusion. When taken in combination, the effects on hemoglobin A1C are additive.
Despite the claims of pharmaceutical marketing, there is little difference among sulfonylureas, metformin, and thiazolidinediones in reduction of hemoglobin A1C. Each class achieves an average reduction of 1% to 2%. Alpha glucosidase inhibitors and nonsulfonylurea secretogogues are probably somewhat less efficacious; combinations of medications seem to be additive.
Clinicians should keep in mind that diet and exercise remain first-line treatment for type 2 diabetes. Initial drug therapy should be guided, however, by evidence about long-term outcomes, such as reduction in the risk of myocardial infarction, renal failure, and blindness; to date, only metformin and sulfonylureas have been shown to be beneficial in reducing microvascular complications. Only metformin has been shown to reduce macrovascular complications and all-cause mortality in obese patients with type 2 diabetes. Interestingly, this beneficial effect of metformin is totally independent of blood sugar control. Thus, metformin should be the pharmaceutical agent of first choice in the treatment of type 2 diabetes.