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Medications> Glucose-lowering>
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DPP-IV Inhibitors

Nadeen Hosein, M.D. and Brian Pinto, Pharm.D.
12-28-2010

INDICATIONS

FDA

  • Type 2 diabetes mellitus

MECHANISM

  • Inhibits the degradation of incretins such as GLP-1 by inhibiting the enzyme dipeptidyl peptidase IV (DPP-IV).  The incretin effect is prolonged, enhancing glycemic control through various mechanisms.

USUAL ADULT DOSING

  • Sitagliptin: recommended dose is 100 mg once a day. Can be taken with or without food. 
  • Saxagliptin: recommended dose is 2.5 or 5 mg once a day. Can be taken with or without food.
  • Janumet: 50/500 mg twice a day, with meals. Can increase to 50/1000 mg twice a day, with meals (maximum dose).
  • If adding sitagliptin or saxagliptin to sulfonylurea therapy, consider decreasing the sulfonylurea dose, to reduce hypoglycemia risk. 
  • Both are FDA approved for use as monotherapy in type 2 diabetes (T2DM).
  • Sitagliptin or saxagliptin can be added to patients already on metformin or thiazolidinediones.
  • In the United States, DPP-IV inhibitors have not been studied for use in combination with insulin.

FORMS

brand 
name
 
generic 
Mfg 
brand 
forms
 
cost* 
Januvia sitagliptin phosphateMerckoral
tablet
25 mg
$214 for 30 tabs
      oral
tablet
50 mg
$214 for 30 tabs
      oral
tablet
100 mg
$214 for 30 tabs
OnglyzasaxagliptinBristol-Myers Squibboral
tablet
2.5 mg
$190 for 30 tabs
      oral
tablet
5 mg
$190 for 30 tabs
Janumetsitagliptin phosphate + metformin hydrochlorideMerck Sharp & Dohme Corp.oral
tablet
50/500 mg
$197 for 60 tabs
      oral
tablet
50/1000 mg
$196 for 60 tabs

*Prices represent cost per unit specified and are representative of "Average Wholesale Price" (AWP). AWP Prices were obtained and gathered by Lakshmi Vasist Pharm D using the Red Book, manufacturer's information, and the McKesson database.

^Dosage is indicated in mg unless otherwise noted.

DOSING IN SPECIAL POPULATIONS

RENAL

  • Sitagliptin: GFR > 50 mL/min, no dosage adjustment needed
  • Sitagliptin: GFR 30-50 mL/min, do not exceed 50 mg daily
  • Sitagliptin: GFR < 30 mL/min, do not exceed 25 mg daily
  • Sitagliptin: for patients on hemodialysis or peritoneal dialysis, do not exceed 25 mg daily
  • Saxagliptin: GFR > 50 mL/min, no dosage adjustment needed
  • Saxagliptin: GFR < 50 mL/min, do not exceed 2.5 mg once daily
  • Saxagliptin: for patients on hemodialysis, administer 2.5 mg once daily, following hemodialysis
  • Janumet: CONTRAINDICATED if GFR < 60 mL/min, or if serum creatinine > 1.4 mg/dL (women) or > 1.5 mg/dL (men)
HEPATIC

  • No dose adjustments needed, except for Janumet: avoid use if liver disease is present, due to increased risk of lactic acidosis
PREGNANCY

  • FDA Category B
BREASTFEEDING

  • Thomson Lactation Ratings: infant risk cannot be ruled out

ADVERSE DRUG REACTIONS

GENERAL

  • Contraindicated in patients with hypersensitivity reaction to sitagliptin or saxagliptin
  • Do not use in diabetic ketoacidosis.
  • Do not use as therapy for type 1 diabetes mellitus.
  • Cases of acute pancreatitis have been reported with sitagliptin: physician should monitor patients closely for signs and symptoms of pancreatitis when starting sitagliptin, or increasing dose.
  • Due to metformin component in Janumet, it is contraindicated in renal disease (see above).
OCCASIONAL

  • Hypoglycemia, more common when used in conjunction with a sulfonylurea.
  • Nasopharyngitis or upper respiratory tract infections
  • Headache
  • Nausea, diarrhea, abdominal pain
  • Urinary tract infections
  • Peripheral edema
  • Janumet: GI disturbance initially (nausea, vomiting, diarrhea) due to metformin; lessened if taken with meals
RARE

  • Acute pancreatitis with sitagliptin
  • Stevens-Johnson syndrome, urticaria, exfoliative dermatitis, and other hypersensitivity skin reactions
  • Anaphylaxis
  • Angioedema
  • Rhabdomyolysis
  • Acute renal failure
  • Bone fractures with saxagliptin
  • Lactic acidosis with Janumet, due to metformin component

DRUG INTERACTIONS

  • Digoxin: Oral sitagliption caused small (11%) increase in AUC and plasma Cmax (18%) of digoxin at 0.25 mg/day. Dose adjustment of digoxin not recommended, but monitor closely.

PHARMACOKINETIC

COMMENTS

  • Overall HbA1c reduction for maximum dose sitagliptin (100 mg daily)  as monotherapy is only about 0.6% after 18 weeks (range 0.5-0.8%) (Raz). This and the high cost have led many endocrinologists to use DPP-IV inhibitors as second or third line drugs when baseline HbA1c is<8%.
  • Sitagliptin is weight-neutral.
  • Long-term safety data is not known for sitagliptin, as it was only released in October 2006.
  • In July 2009, FDA approved new DPP-IV inhibitor, saxagliptin (Onglyza), for T2DM (Rosenstock).
  • Other DPP-IV inhibitors, (such as vildagliption and alogliptin), are not yet FDA approved.
  • In Europe, vildagliptin is widely approved, and sitagliptin was recently approved as add-on therapy to insulin

REFERENCES

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