III. 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)

IV. 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

V. 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
    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

VI. Mechanism

  1. Blocks Dipeptidyl Peptidase-4 Inhibitor (DPP-4) allowing 2-3x accumulation of GLP-1
  2. Differs from Byetta: Weight neutral, no Nausea

VII. 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

VIII. Preparations: Combination

  1. Kanzano (Alogliptin and Metformin)
  2. Oseni (Alogliptin and Pioglitazone)

IX. 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

X. References

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Cost: Medications

januvia (on 6/8/2017 at Medicaid.Gov Survey of pharmacy drug pricing)
JANUVIA 100 MG TABLET $12.67 each
JANUVIA 25 MG TABLET $12.80 each
JANUVIA 50 MG TABLET $12.68 each
onglyza (on 2/22/2017 at Medicaid.Gov Survey of pharmacy drug pricing)
ONGLYZA 2.5 MG TABLET $12.29 each
ONGLYZA 5 MG TABLET $12.34 each
tradjenta (on 2/22/2017 at Medicaid.Gov Survey of pharmacy drug pricing)
TRADJENTA 5 MG TABLET $12.23 each
alogliptin (on 4/19/2017 at Medicaid.Gov Survey of pharmacy drug pricing)
ALOGLIPTIN 12.5 MG TABLET Generic $6.09 each
ALOGLIPTIN 25 MG TABLET Generic $5.67 each
ALOGLIPTIN 6.25 MG TABLET Generic $5.61 each
ALOGLIPTIN-METFORMIN 12.5-1000 Generic $2.71 each
ALOGLIPTIN-METFORMIN 12.5-500 Generic $3.00 each
ALOGLIPTIN-PIOGLIT 25-15 MG TB Generic $6.44 each
ALOGLIPTIN-PIOGLIT 25-30 MG TB Generic $6.48 each
nesina (on 2/22/2017 at Medicaid.Gov Survey of pharmacy drug pricing)
NESINA 25 MG TABLET Generic $5.67 each

Ontology: sitagliptin (C1565750)

Definition (NCI) An orally available, competitive, beta-amino acid-derived inhibitor of dipeptidyl peptidase 4 (DDP-4) with hypoglycemic activity. Sitagliptin may cause an increased risk in the development of pancreatitis.
Concepts Organic Chemical (T109) , Pharmacologic Substance (T121)
MSH C496398
SnomedCT 424106006, 423307000
English 4-oxo-4-(3-(trifluoromethyl)-5,6-dihydro(1,2,4)triazolo(4,3-a)pyrazin-7(8H)-yl)-1-(2,4,5-trifluorophenyl)butan-2-amine, sitagliptin, Sitagliptin (product), Sitagliptin, Sitagliptin (substance), SITAGLIPTIN, sitagliptin [Chemical/Ingredient], sitaGLIPtin
Spanish sitagliptina (producto), sitagliptina, sitagliptina (sustancia)

Ontology: Januvia (C1702177)

Concepts Organic Chemical (T109) , Pharmacologic Substance (T121)
MSH C496398
English Januvia

Ontology: Dipeptidyl-Peptidase IV Inhibitors (C1827106)

Definition (MSH) Compounds that suppress the degradation of INCRETINS by blocking the action of DIPEPTIDYL-PEPTIDASE IV. This helps to correct the defective INSULIN and GLUCAGON secretion characteristic of TYPE 2 DIABETES MELLITUS by stimulating insulin secretion and suppressing glucagon release.
Concepts Pharmacologic Substance (T121)
MSH D054873
SnomedCT 423837000, 422403005
English Dipeptidyl peptidase IV inhibitor, Dipeptidyl peptidase IV inhibitor (substance), Dipeptidyl peptidase IV inhibitor (product), Gliptins, Dipeptidyl Peptidase IV Inhibitors, Inhibitors, Dipeptidyl-Peptidase IV, Dipeptidyl-Peptidase IV Inhibitors, Dipeptidyl-Peptidase 4 Inhibitors, Dipeptidyl Peptidase 4 Inhibitors
Spanish inhibidor de dipeptidil peptidasa IV (sustancia), inhibidor de dipeptidil peptidasa IV (producto), inhibidor de dipeptidil peptidasa IV, Inhibidores de Dipeptidil-Peptidasa IV, Gliptinas
Portuguese Gliptinas, Inibidores da Dipeptidil Peptidase IV
Finnish Dipeptidyylipeptidaasi IV:n salpaajat
French Gliptines, Inhibiteurs de la dipeptidyl-peptidase de type 4, Inhibiteurs de la dipeptidyl-peptidase IV
German Gliptine, Dipeptidyl-Peptidase IV-Inhibitoren, DPP IV-Inhibitoren
Italian Gliptine, Inibitori della dipeptidil peptidasi IV
Russian DIPEPTIDIL-PEPTIDAZY IV INGIBITORY, GLIPTINY, ДИПЕПТИДИЛ-ПЕПТИДАЗЫ IV ИНГИБИТОРЫ, ГЛИПТИНЫ
Czech gliptiny, DPP-4 inhibitory, dipeptidylpeptidasa IV - inhibitory, inhibitory DPP-4, inhibitory dipeptidylpeptidázy 4
Swedish Dipeptidylpeptidas IV-hämmare
Polish Inhibitory dipeptydylopeptydazy IV, Gliptyny, Inhibitory peptydazy dipeptydylowej IV
Japanese ジペプチジルペプチダーゼIV阻害剤, DPP-4阻害薬, DPP-IV阻害薬, ジペプチジルペプチダーゼIV阻害薬, DPP-IV阻害剤