Level 3: Lacking direct evidence

A systematic review of 216 randomized trials lasting at least three months compared oral diabetes medications with placebo or head-to-head with other oral diabetes medications in adults with type 2 diabetes (AHRQ Comparative Effectiveness Review of Oral Diabetes Medications for Adults with Type 2 Diabetes. July 8, 2007; available online free of charge at: http://effectivehealthcare.ahrq.gov/repFiles/OralFullReport.pdf, accessed January 10, 2008).

Most available oral antidiabetic agents appeared similarly effective for glycemic control and other surrogate outcomes (BP, lipid profile). Combination therapy yielded a greater reduction in hemoglobin A1c than monotherapy. Most drugs had similarly minimal effects on systolic and diastolic BP (<5 mm Hg).

Glitazones increased LDL by about 10 mg/dL while metformin decreased LDL about the same amount; other medications had minimal effects. Glitazones increased HDL by about 3-5 mg/dL compared with metformin or second-generation sulfonylureas. Except for rosiglitazone, most oral medications decreased triglycerides.


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Hypoglycemic episodes were more frequent with second-generation sulfonylureas and repaglinide compared with other oral agents. Glyburide was associated with a higher absolute risk (2%) of hypoglycemia compared with other second-generation sulfonylureas. GI adverse events were more common with metformin (2%-63%) and acarbose (15%-30%). Congestive heart failure was more common with glitazones than metformin or the sulfonylureas. Edema and anemia were generally more common with glitazones than other oral diabetes medications.

Except for weight-neutral metformin and acarbose, most patients taking oral medications gained 1-5 kg (2.2-11 lb).Evidence was insufficient to draw conclusions about clinical outcomes; differences among oral medications in all-cause mortality, peripheral vascular disease, quality of life, and functional status; or differences in microvascular outcomes.