Comparing Safety and Efficacy of Medications for Type 2 Diabetes

Older (and therefore cheaper) drugs are as good as, or better than, newer ones.

Recent concerns about the risks associated with rosiglitazone (a thiazolidinedione) have increased interest in the safety and efficacy of all oral agents for type 2 diabetes. Researchers recently reviewed the literature to summarize the risks and benefits of these drugs; they identified 216 controlled trials and cohort studies and two systematic reviews.

Too few randomized controlled trials have been performed to provide definitive comparative evidence regarding effects on mortality and diabetes-related morbidity. Most agents improved hemoglobin A_1C to the same degree as second-generation sulfonylureas (by about 1%); adding a second agent led to an additional one-percentage-point decrease. Nateglinide (Starlix; a nonsulfonylurea insulin secretagogue) and -glucosidase inhibitors (e.g., acarbose, or Precose) were associated with smaller A_1C reductions. Thiazolidinediones increased both HDL and LDL cholesterol levels; metformin decreased LDL cholesterol levels. Unlike metformin and acarbose, other agents led to weight gain. Hypoglycemia risk was greater with sulfonylureas or repaglinide (Prandin) than with metformin or thiazolidinediones. Lactic acidosis did not differ between metformin and other agents. Risks for edema, mild anemia, and congestive heart failure were higher with thiazolidinediones, although the absolute risk increase for CHF was small. Risk for elevated liver enzymes was similar for metformin, sulfonylureas, and thiazolidinediones.

Comment: We need more data comparing the effects of oral diabetes medications on morbidity and mortality. But based on the current evidence, metformin appears to be a good first choice in the absence of contraindications. Adding a second agent (which could be a sulfonylurea, given similar effectiveness and fewer or at least similar risks) makes sense when needed.

— Richard Saitz, MD, MPH, FACP, FASAM

Published in Journal Watch General Medicine July 26, 2007

Citation(s):

Bolen S et al. Systematic Review: Comparative effectiveness and safety of oral medications for type 2 diabetes mellitus. Ann Intern Med 2007 Jul 16; [e-pub ahead of print].