Sitagliptin

Severe and disabling arthralgia has been reported with DPP-IV inhibitor use; onset may occur within one day to years after treatment initiation and may resolve with discontinuation of therapy. Some patients may experience a recurrence of symptoms if DPP-IV inhibitor therapy resumed.

DPP-4 inhibitor use has been associated with development of bullous pemphigoid; cases have typically resolved with topical or systemic immunosuppressive therapy and discontinuation of DPP-4 inhibitor therapy. Advise patients to report development of blisters or erosions. Discontinue therapy if bullous pemphigoid is suspected and consider referral to a dermatologist.

Serious hypersensitivity reactions, including anaphylaxis, angioedema, and exfoliative skin reactions, such as Stevens-Johnson syndrome, have been reported; discontinue if signs/symptoms of hypersensitivity reactions occur. Events have generally been noted within the first 3 months of therapy, and may occur with the initial dose. Use with caution if patient has experienced angioedema with other dipeptidyl peptidase IV (DPP-IV) inhibitor use.

Cases of acute pancreatitis (including hemorrhagic and necrotizing with some fatalities) have been reported with use. Monitor for signs/symptoms of pancreatitis; discontinue use immediately if pancreatitis is suspected and initiate appropriate management. Use with caution in patients with a history of pancreatitis as it is not known if this population is at greater risk.

Worsening renal function, including acute renal failure, sometimes requiring dialysis has been reported. Disease-related concerns:

In cardiovascular outcome trials of patients with type 2 diabetes and atherosclerotic cardiovascular disease, treatment with other DPP-4 inhibitors has been associated with heart failure. Use sitagliptin with caution in patients at risk for heart failure (eg, history of heart failure or renal impairment) and monitor for signs and symptoms of heart failure during therapy; consider discontinuation if heart failure develops. In a scientific statement from the American Heart Association, sitagliptin has been determined to be an agent that may exacerbate underlying myocardial dysfunction (magnitude: major) (AHA [Page 2016]). However, in one large randomized, double-blinded trial in patients with type 2 diabetes and established cardiovascular disease (history of major CAD, ischemic cerebrovascular disease, or atherosclerotic peripheral arterial disease), the occurrence of the primary composite cardiovascular outcome (cardiovascular death, nonfatal MI, nonfatal stroke, or hospitalization for unstable angina) with sitagliptin was found to be noninferior to placebo. In addition, the rate of hospitalization for heart failure did not differ between the two groups (Green 2015; McGuire 2016).

Use with caution in patients with moderate to severe renal dysfunction and end-stage renal disease (ESRD) requiring hemodialysis or peritoneal dialysis; dosing adjustment required. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Other warnings/precautions:

Not indicated for use in patients with insulin-dependent diabetes mellitus (IDDM) (type 1) or in patients with diabetic ketoacidosis (DKA).

Diabetes self-management education is essential to maximize the effectiveness of therapy.