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Nadeen Hosein, M.D. and Brian Pinto, Pharm.D.
12-28-2010
- 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.
- 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.
brand name
| generic
| Mfg
| brand forms
| cost*
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Januvia | sitagliptin phosphate | Merck | oral tablet 25 mg | $214 for 30 tabs |
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| oral tablet 50 mg | $214 for 30 tabs |
|
|
| oral tablet 100 mg | $214 for 30 tabs |
Onglyza | saxagliptin | Bristol-Myers Squibb | oral tablet 2.5 mg | $190 for 30 tabs |
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| oral tablet 5 mg | $190 for 30 tabs |
Janumet | sitagliptin phosphate + metformin hydrochloride | Merck Sharp & Dohme Corp. | oral tablet 50/500 mg | $197 for 60 tabs |
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| 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.
- 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)
- No dose adjustments needed, except for Janumet: avoid use if liver disease is present, due to increased risk of lactic acidosis
- Thomson Lactation Ratings: infant risk cannot be ruled out
- 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).
- 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
- 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
- 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.
- 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
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