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

  • Precautions
  1. Gliptins are less than half as effective as lower cost medications (e.g. Metformin, Sulfonylureas)
  2. Indicated for those close to goal who are already either on other Oral Hypoglycemics or in whom they are contraindicated (e.g. Chronic Kidney Disease)
  • 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
  • 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. Scirica (2013) N Engl J Med 369(14):1317-26 [PubMed]
  5. Severe, persistent Joint Pain
    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
  • Mechanism
  1. Blocks Dipeptidyl Peptidase-4 Inhibitor (DPP-4) allowing 2-3x accumulation of GLP-1
  2. Differs from Byetta: Weight neutral, no Nausea
  • 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. 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
  • Preparations
  • Combination
  1. Kanzano (Alogliptin and Metformin)
  2. Oseni (Alogliptin and Pioglitazone)
  • Efficacy
  1. Lowers HBA1C 0.6%
    1. Contrast with Metformin, Sulfonylureas, GLP-1 Agonists and Pioglitazone that lower A1C 1.0 to 1.5% at generic costs
  • References