Interactive diabetes case 17: A 47-year-old patient with newly discovered type 2 diabetes – A5

ANSWER — Incorrect.

Sitagliptin was the first of a new class of agents marketed for the treatment of diabetes, the dipeptidyl peptidase 4 (DPP-4) inhibitors. Agents in this class inhibit the breakdown of endogenous glucagon-like peptide 1 (GLP-1) and other incretins. Thus, their biological effects are similar, but not identical, to those of GLP-1 receptor agonists such as exenatide. (See "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus".)

Although sitagliptin is approved for use by the US Food and Drug Administration (FDA), there is little published long-term information about its clinical effects and side effects. Like the GLP-1 receptor agonists, the DPP-4 inhibitors are indicated for patients with type 2 diabetes but not those with type 1 diabetes.

The DPP-4 inhibitors are given orally. In patients with chronic kidney disease (estimated glomerular filtration rate [eGFR] <30 ml/min/1.73²), linagliptin is the preferred DPP-4 inhibitor. It is primarily eliminated via the enterohepatic system and is the only DPP-4 inhibitor that does not require dose adjustment in individuals with impaired kidney function. They are expensive. In postmarketing reports, sitagliptin has been associated with hypersensitivity reactions including anaphylaxis, angioedema, and blistering skin conditions, including Stevens-Johnson syndrome. (See "Dipeptidyl peptidase 4 (DPP-4) inhibitors for the treatment of type 2 diabetes mellitus", section on 'Patient selection'.)

The FDA issued an alert about a possible association of incretin-based drugs such as sitagliptin (and exenatide) 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 agree that there is insufficient evidence to confirm an increased risk of pancreatitis or pancreatic cancer with the use of GLP-1-based therapies [1]. Pancreatitis continues to be considered a risk associated with these drugs. Concerns remain, and monitoring for and reporting of pancreatic adverse effects continues.

Sitagliptin has not been shown to be superior to any other single pharmacologic agent in a direct comparison. Because of its high cost and the poorly defined potential for serious and life-threatening hypersensitivity reactions, sitagliptin cannot be recommended as the initial pharmacologic agent in patients with type 2 diabetes. It may have an occasional role as a third oral agent in patients with a modest increase in the glycated hemoglobin (A1C) level who cannot or will not take insulin or a GLP-1 receptor agonist when full doses of metformin and a sulfonylurea or other second agent have not produced satisfactory metabolic control.

Return to the beginning to try again. (See "Interactive diabetes case 17: A 47-year-old patient with newly discovered type 2 diabetes".)