USMLE STEP 3 MCQ 35:An elderly woman with type 2 diabetes


An elderly woman with type 2 diabetes has poorly controlled blood glucose levels despite treatment with metformin. The physician decides to try pioglitazone.
Which best describes the mode of action of pioglitazone?


a) reduces insulin resistance and improves insulin sensitivity
b) suppresses basal hepatic glucose production
c) reduces fasting plasma glucose
d) activates the AMP-activated protein kinase
e) stimulates first-phase insulin secretion in the pancreatic beta cells

 Correct Answer: A


An elevated rate of basal hepatic glucose output is the primary determinant of elevated fasting blood glucose levels in patients with type 2 diabetes. The primary effect of metformin is the suppression of basal hepatic glucose production, thereby reducing fasting plasma glucose . Metformin does not stimulate insulin secretion; in contrast, metformin reduces fasting plasma insulin and improves whole-body insulin-stimulated glucose metabolism (insulin sensitivity). While it is possible that the beneficial effect of metformin on insulin sensitivity is mediated directly, a more likely explanation is that it is secondary to a reduction in hyperglycemia, triglycerides, and free fatty acids. Recent in vitro and in vivo evidence has shown that metformin activates the AMP-activated protein kinase

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