Gliptin

Aka: Gliptin, DPP-4 Inhibitor, Dipeptidyl Peptidase-4 Inhibitor, Dipeptidyl-Peptidase IV Inhibitor, DPP-4, Sitagliptin, Januvia, Saxagliptin, Onglyza, Linagliptin, Tradjenta, Alogliptin, Nesina

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