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Exenatide
58%
28/48
Glipizide
15%
7/48
Repaglinide
8%
4/48
Pioglitazone
10%
5/48
Sitagliptin
6%
3/48
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This patient presents needing a second agent to achieve glycemic control and desiring to lose additional weight. Since GLP-1 mimetics have been shown to cause weight loss, exenatide would be the best choice as a second agent for this patient. In patients with inadequate glycemic control on metformin and HbA1c >8.5%, a second pharmacologic agent may be added. The choice of a second agent depends upon multiple factors, including the risk of hypoglycemia and patient preference. A sulfonylurea like glipizide is often used, although a meglitinide (e.g. repaglinide), thiazolidinedione (e.g. pioglitazone), or GLP-1 agonist (e.g. exenatide) may also be used as second-line therapy. GLP-1 agonists in particular have been shown to cause weight loss and are often specifically used to take advantage of that side effect. Incorrect Answers: Answer 2: Glipizide is a sulfonylurea, which stimulates postprandial insulin release by closing the potassium channel on the beta-cell membrane. They have been shown to cause hypoglycemia and weight gain. Answer 3: Repaglinide is a meglitinide, which similarly stimulates postprandial insulin release by binding to potassium channels on the beta-cell membrane. Like sulfonylureas, they have been shown to cause hypoglycemia and weight gain. Answer 4: Pioglitazone is a thiazolidinedione (TZD), which increases peripheral insulin sensitivity by binding to the PPAR-gamma nuclear transcription regulator. They have been shown to cause weight gain, peripheral edema resulting in congestive heart failure, and increased risk of fractures. Answer 5: Sitagliptin is a DPP-4 inhibitor, which inhibits the DPP-4 enzyme that deactivates GLP-1, thereby increasing glucose-dependent insulin release. They have a low risk of hypoglycemia but have been shown to be weight-neutral. Bullet Summary: In patients that require a second medication to achieve glycemic control, the second agent is chosen based on patient preference, the risk of hypoglycemia, and other side effects, including effects on weight. GLP-1 agonists like exenatide have been shown to lead to weight loss.
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