Oral antihyperglycemic therapy for type 2 diabetes: scientific review.
BACKGROUND
Care of patients with type 2 diabetes has been revolutionized throughout the past several years-first, by the realization of the importance of tight glycemic control in forestalling complications, and second, by the availability of several unique classes of oral antidiabetic agents. Deciphering which agent to use in certain clinical situations is a new dilemma facing the primary care physician.


OBJECTIVE
To systematically review available data from the literature regarding the efficacy of oral antidiabetic agents, both as monotherapy and in combination.


METHODS
A MEDLINE search was performed to identify all English-language reports of unique, randomized controlled clinical trials involving recently available oral agents for type 2 diabetes. Bibliographies were also reviewed to find additional reports not otherwise identified.


METHODS
Studies (63) were included in the analysis if they had a study period of at least 3 months; if each group contained at least 10 subjects at the study's conclusion; and if hemoglobin A(1c) was reported. When multiple dosages of a drug were tested, the results of the highest approved dosage were used. In placebo-controlled trials, hemoglobin A(1c) data are presented as the difference between the change in treated vs placebo subjects.


RESULTS
Five distinct oral drug classes are now available for the treatment of type 2 diabetes. Compared with placebo treatment, most of these agents lower hemoglobin A(1c) levels approximately 1% to 2%. Equivalent efficacy is usually demonstrated when different agents are compared with one another in the same study population. When they are used in combination, there are additional glycemic benefits. Long-term vascular risk reduction has been demonstrated only with sulfonylureas and metformin.


CONCLUSIONS
With few exceptions, the available oral antidiabetic agents are equally effective at lowering glucose concentrations. Their mechanisms of action are different, however, and as a result they appear to have distinct metabolic effects. These are reflected in their adverse effect profiles and their effect on cardiovascular risk, which may influence drug choice.
Inzucchi
Silvio E
SE
Endocrinology, TMP 534, Yale School of Medicine, Box 208020, New Haven, CT 06520, USA. silvio.inzucchi@yale.edu
D000284:Administration, Oral; D001645:Biguanides / Q000627:therapeutic use; D001786:Blood Glucose / Q000378:metabolism; D002219:Carbamates / Q000627:therapeutic use; D002839:Chromans / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000628:therapy; D004032:Diet; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015444:Exercise; D006442:Glycated Hemoglobin / Q000378:metabolism; D065089:Glycoside Hydrolase Inhibitors; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000145:classification* / Q000627:therapeutic use*; D008687:Metformin / Q000627:therapeutic use; D010880:Piperidines / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D013453:Sulfonylurea Compounds / Q000627:therapeutic use; D013844:Thiazoles / Q000627:therapeutic use; D045162:Thiazolidinediones; D000077288:Troglitazone
D001645:Biguanides; D001786:Blood Glucose; D002219:Carbamates; D002839:Chromans; D004791:Enzyme Inhibitors; D006442:Glycated Hemoglobin; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents; D008687:Metformin; D010880:Piperidines; D013453:Sulfonylurea Compounds; D013844:Thiazoles; D045162:Thiazolidinediones; D000077288:Troglitazone; C072379:repaglinide