Weight gain, edema (fluid retention), hepatotoxicity, and heart failure are toxicities associated with pioglitazone. The drug should not be administered to patients with heart failure or liver disease.
Pioglitazone and rosiglitazone are thiazolidinedione derivatives that reduce insulin resistance in patients with DM2. They are occasionally used as monotherapy for DM2 but are most often combined with other hypoglycemics. The drugs are also used to treat polycystic ovarian syndrome.
Scott discusses the use of piogliazone in DM2. One trial found that pioglitazone may lead to a statistically significant reduction in morbidity and mortality in patients with established macrovascular disease but may also increase the likelihood of hospitalization for heart failure.
Tack et al. review the use of thiazolidinedione derivatives in diabetes mellitus type two. Because of drug associated fluid retention, all forms of heart failure are a contraindication for using thiazolidinediones (TZDs). Liver enzyme disorders are also a contraindication for the use of TZDs. Plasma concentrations of gamma glutamyl transferase (gGT) and of ALAT (alanine aminotransferase) should first be determined prior to treatment.
Illustration A diagrams the mechanism of action of the thiazolidinedione derivatives, which lower blood glucose by activating peripheral PPAR-gamma receptors.
Answer 1: Glargine is a long-acting insulin analog. Like other insulin analogs, toxicities include hypoglycemia and rare hypersensitivity reactions.
Answer 2: Glipizide is a second-generation sulfonylurea used to stimulate release of endogenous insulin in DM2. Toxicities include hypoglycemia and weight gain. It is metabolized by the liver and should be used with caution in those with liver disease.
Answer 3: Metformin, a biguanide, is the first line therapy for patients with DM2. Toxicities include lactic acidosis; the drug is contraindicated in patients with renal failure.
Answer 5: Pramlintide is an amylin mimetic used as an insulin-adjunct in diabetes mellitus types 1 and 2 to decrease glucagon secretion and slow gastric emptying. Toxicities include hypoglycemia, nausea, and diarrhea
Scott T. Does pioglitazone benefit patients with type 2 diabetes? Am Fam Physician. 2007 Oct 1;76(7):969-70. Review
PMID:17956065 (Link to Abstract)
Tack CJ, Smits P. Thiazolidinedione derivatives in type 2 diabetes mellitus. Neth J Med. 2006 Jun;64(6):166-74. Review
PMID:16788214 (Link to Abstract)
USMLE World Step 1 QBank Question #604. Copyright © USMLEWorld, LLC 2012