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Gliptin
Aka: Gliptin, DPP-4 Inhibitor, Dipeptidyl Peptidase-4 Inhibitor, Dipeptidyl-Peptidase IV Inhibitor, DPP-4, Sitagliptin, Januvia, Saxagliptin, Onglyza, Linagliptin, Tradjenta, Alogliptin, Nesina
- See Also
- Incretin Mimetic
- Byetta
- Indications
- Type II Diabetes Mellitus
- Insulin deficiency and Insulin Resistance
- Adjunct to Glucophage, Sulfonylureas, Glitazones
- Mechanism
- Blocks Dipeptidyl Peptidase-4 Inhibitor (DPP-4) allowing 2-3x accumulation of GLP-1
- Reduce Incretin degradation
- Differs from Byetta: Weight neutral, no Nausea
- Precautions
- Gliptins are less than half as effective as lower cost medications (e.g. Metformin, Sulfonylureas)
- No longterm evidence of improved outcomes
- Expensive (>$400/month)
- Decrease dose in renal Impairment
- May consider for those close to goal AND
- Already either on other Oral Hypoglycemics or in whom they are contraindicated (e.g. Chronic Kidney Disease)
- Contraindications
- Type I Diabetes Mellitus
- Prior history of malignancy
- Due to increased risk of cancer invasion and metastases
- Women of child bearing age (relative contraindication)
- Teratogenicity risk
- Congestive Heart Failure
- Adverse Effects
- Acute Pancreatitis
- Incidence may be as high as 1 in 50 for two years
- Singh (2013) JAMA Intern Med 173(7):534-9 [PubMed]
- Serious Allergic Reaction (Sitagliptin)
- Anaphylaxis
- Angioedema
- Hepatotoxicity (Vildagliptin)
- Congestive Heart Failure exacerbation
- Risk of hospitalized CHF exacerbation: 1 in 150 patients/2 years using Saxigliptin or Alogliptin
- Sitagliptin (Januvia) is less associated with CHF exacerbation
- Scirica (2013) N Engl J Med 369(14):1317-26 [PubMed]
- Severe, persistent Joint Pain (rare)
- Stop agent if suspect Gliptin-induced pain (and avoid other Gliptins)
- Consider other possible causes (e.g. Statin induced Myopathy)
- FDA Alert
- http://www.fda.gov/drugs/drugsafety/ucm459579.htm
- Preparations
- Sitagliptin (Januvia)
- May be dosed with or without food
- Fewer Drug Interactions than Saxagliptin (Onglyza) and Linagliptin (Tradjenta)
- Standard dosing
- Creatinine Clearance >50 ml/min: 100 mg once daily
- Renal Insufficiency
- Consider Tradjenta instead, as does not require Renal Dosing adjustment
- Creatinine Clearance 30-49 ml/min: 50 mg once daily
- Creatinine Clearance <30 ml/min: 25 mg once daily
- Saxagliptin (Onglyza)
- Significant CYP3A4 Drug Interactions
- Adjust for renal Impairment
- CHF risk
- Linagliptin (Tradjenta)
- Significant CYP3A4 inducer and P-Glycoprotein Inducer
- No Renal Dosing required
- Alogliptin (Nesina)
- Fewer Drug Interactions than Saxagliptin (Onglyza) and Linagliptin (Tradjenta)
- Adjust for renal Impairment
- CHF risk
- First Gliptin to be generic as of 2016
- Preparations: Combination
- Kanzano (Alogliptin and Metformin)
- Oseni (Alogliptin and Pioglitazone)
- Janumet (Stagliptin and Metformin)
- Trijardy XR (Linagliptin, Empagliflozin and Metformin XR)
- Efficacy
- No longterm cardiovascular benefit
- Green (2015) N Engl J Med 373(3): 232-42 [PubMed]
- Scirica (2013) N Engl J Med 369(14): 1317-26 [PubMed]
- White (2013) N Engl J Med 369(14): 1327-35 [PubMed]
- Lowers HBA1C 0.6%
- Contrast with Metformin, Sulfonylureas, GLP-1 Agonists, Pioglitazone lower A1C 1.0 to 1.5% at generic costs
- References
- (2013) Presc Lett 20(8):46
- Jones (2007) Am Fam Physician 75:1831-5 [PubMed]
- Steinberg (2019) Am Fam Physician 99(4): 237-43 [PubMed]