Balancing risk and benefit with oral hypoglycemic drugs

Mt Sinai J Med. 2009 Jun;76(3):234-43. doi: 10.1002/msj.20116.


Clinicians are faced with an expansive array of treatment choices when caring for patients with type 2 diabetes. Because patient compliance may be affected when media sensationalism about controversial findings is misunderstood, we sought to clarify the recent controversy surrounding the cardiovascular and bone-health risks of thiazolidinediones, the risk of lactic acidosis with metformin, and the risk of hypoglycemia with oral therapies. The side effect profile of thiazolidinediones includes fluid retention, heart failure; and an increased risk of fracture. A recent controversial meta-analysis suggested that rosiglitazone increases the risk of myocardial infarction, which is possibly related to thiazolidinedione-induced lipid changes, weight gain, congestive heart failure, and anemia. Metformin is restricted to patients with normal renal function because of concerns that metformin may cause lactic acidosis. However, few cases of metformin-associated lactic acidosis have been reported, and most have occurred in patients with other reasons for developing lactic acidosis, such as sepsis or renal failure. Although the use of metformin continues to increase, observational studies have not been able to demonstrate an increased incidence of lactic acidosis in metformin-treated patients, even when it is used in populations with relative contraindications. Some oral hypoglycemic medications can cause hypoglycemia. Hypoglycemia is especially common in older patients, alcoholics, and patients with liver or renal disease. Patients on sulfonylureas and meglitinides have the highest incidence of hypoglycemia because of their pharmacological action of increasing insulin secretion. Of the sulfonylureas, glyburide presents the highest risk of hypoglycemia. Combination therapies, especially those regimens containing a sulfonylurea, increase the risk of hypoglycemia.

MeSH terms

  • Acidosis, Lactic / chemically induced
  • Administration, Oral
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Drug Therapy, Combination
  • Humans
  • Hypoglycemia / chemically induced
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / adverse effects*
  • Metformin / administration & dosage
  • Metformin / adverse effects
  • Myocardial Infarction / chemically induced
  • Risk Assessment
  • Thiazolidinediones / administration & dosage
  • Thiazolidinediones / adverse effects
  • Treatment Outcome


  • Hypoglycemic Agents
  • Thiazolidinediones
  • Metformin