Interactive diabetes case 16: A 61-year-old patient with uncontrolled type 2 diabetes on two oral agents – A2

ANSWER — Incorrect.

The choice of a pharmacologic agent when lifestyle change and maximum tolerated doses of two oral agents do not achieve target glycemia should be individualized (see "Management of persistent hyperglycemia in type 2 diabetes mellitus", section on 'Dual agent failure'). This patient does not have established atherosclerotic cardiovascular disease (ASCVD) or chronic kidney disease, so there is no strong indication for a glucagon-like peptide 1 (GLP-1) receptor agonist or a sodium-glucose cotransporter 2 (SGLT2) inhibitor [1]. Cost is a major concern for this patient, so a basal insulin with a low acquisition cost is preferable.

Exenatide (synthetic exendin-4) is a GLP-1 agonist.

GLP-1, 7-37, a naturally occurring peptide produced by the L-cells of the small intestine, stimulates endogenous insulin secretion. Exenatide, which is structurally homologous with GLP-1, has the same effect, but has a longer circulating half-life than GLP-1 and is suitable for clinical use. It is administered by subcutaneous injection twice a day before meals. Exenatide also reduces glucagon secretion and decreases gastric motility. Its effect on glucose levels is predominantly postprandial. Exenatide reduces glycated hemoglobin (A1C) values by approximately 1.0 percent (table 1).

Exenatide causes gastrointestinal (GI) side effects (notably nausea, vomiting, and diarrhea) in a large proportion of patients. Its use is associated with modest weight loss, due at least in part to the GI side effects. (Occasionally a patient will experience appreciable weight loss.) It should not be used in patients with gastroparesis. It is expensive.

The US Food and Drug Administration (FDA) issued an alert about a possible association of incretin-based drugs such as exenatide (and sitagliptin) with acute pancreatitis based upon a review of 30 postmarketing reports, in some of which a causal relationship between these agents and acute pancreatitis was suspected. The FDA and the European Medicines Agency now agree that there is insufficient evidence to confirm an increased risk of pancreatitis or pancreatic cancer with the use of GLP-1-based therapies [2]. Pancreatitis continues to be considered a risk associated with these drugs. Concerns remain, and monitoring for and reporting of pancreatic adverse effects continues. Exenatide is contraindicated in patients with a personal or family history of medullary thyroid carcinoma and in patients with the multiple endocrine neoplasia syndrome type 2.

If a GLP-1 receptor agonist is chosen because of the presence of known ASCVD, the strongest evidence is for dulaglutide, liraglutide, and semaglutide [1].

Return to the beginning to try again. (See "Interactive diabetes case 16: A 61-year-old patient with uncontrolled type 2 diabetes on two oral agents".)