A 56-year-old woman comes to the office for follow-up of type 2 diabetes mellitus. She is managing her condition with a healthy diet and regular exercise and is on the maximum tolerated dose of metformin. Despite this, the patient's diabetes has been inadequately controlled for the last 6 months, with an average fasting glucose level of 170 mg/dL and a hemoglobin A1c of 8.0%. She has no known diabetes-related complications. Medical history includes hypertension, for which she takes lisinopril and amlodipine. After discussing various medication options, it is decided to add pioglitazone to her current regime. Before starting this medication, this patient should be educated about which of the following adverse drug effects?

Question

A 56-year-old woman comes to the office for follow-up of type 2 diabetes mellitus.  She is managing her condition with a healthy diet and regular exercise and is on the maximum tolerated dose of metformin.  Despite this, the patient's diabetes has been inadequately controlled for the last 6 months, with an average fasting glucose level of 170 mg/dL and a hemoglobin A1c of 8.0%.  She has no known diabetes-related complications.  Medical history includes hypertension, for which she takes lisinopril and amlodipine.  After discussing various medication options, it is decided to add pioglitazone to her current regime.  Before starting this medication, this patient should be educated about which of the following adverse drug effects?

Quizplus · Accepted Answer

11ec160b_3bac_9521_9249_d9c065481c67_MD0001_00 Thiazolidinediones (TZDs) (eg, pioglitazone) activate peroxisome proliferator-activated receptor gamma, a transcriptional regulator that affects expression of genes involved in glucose and lipid metabolism. TZDs cause reduced insulin resistance and a decrease in blood glucose levels. Because their effect requires an alteration in gene transcription and protein synthesis, maximal glucose lowering may take place days to weeks after initiating therapy. The main side effect of TZDs is fluid retention due to increased sodium reabsorption in the renal collecting tubules and increased vascular permeability in adipose tissue. This can cause water weight gain, peripheral edema, and decompensation of underlying congestive heart failure. Fluid retention is often worse when TZDs are given with insulin. TZDs also cause adipose weight gain, likely due to increased fat storage in adipocytes and an increased number of adipocytes in subcutaneous tissue. (Choice A) Agranulocytosis is seen with certain antithyroid medications (eg, methimazole) and is a rare complication of sulfonylurea therapy. It is not seen with TZDs. (Choice B) Hepatic toxicity was seen with an older TZD, troglitazone, which is no longer available. The current TZDs (pioglitazone and rosiglitazone) do not cause significant hepatotoxicity. (Choice C) TZDs increase insulin sensitivity rather than insulin secretion. As a result, they have a low risk of hypoglycemia, although they can increase the risk if used in combination with insulin or sulfonylureas. (Choice D) Lactic acidosis is a potential side effect of metformin, although it is rare when used in patients with normal renal, hepatic, and cardiac function. (Choice E) Sodium-glucose cotransporter 2 inhibitors (eg, canagliflozin) can induce osmotic diuresis, leading to volume depletion and orthostatic hypotension. TZDs do not commonly cause orthostatic hypotension. Educational objective: Thiazolidinediones (eg, pioglitazone) can cause fluid retention, leading to peripheral edema and weight gain. The excess fluid can potentially exacerbate underlying congestive heart failure. __________ References: Thiazolidinediones and risk of heart failure in patients with or at high risk of type 2 diabetes mellitus: a meta-analysis and meta-regression analysis of placebo-controlled randomized clinical trials. (http://www.ncbi.nlm.nih.gov/pubmed/21294599)

A 56-Year-Old Woman Comes to the Office for Follow-Up of Type