II. Indications
- Type II Diabetes Mellitus
-
Insulin deficiency and Insulin Resistance
- Adjunct to Glucophage, Sulfonylureas, Glitazones
III. Contraindications
- Type I Diabetes Mellitus
- Congestive Heart Failure
- Prior history of malignancy
- Due to increased risk of cancer invasion and metastases
IV. Mechanism
- See DPP-4 Inhibitor
- Dipeptidyl Peptidase-4 (DPP-4) is an enzyme that degrades the Incretins GLP-1 and GLP-2
- DPP4 Inhibitor Activity
- DPP-4 Inhibitors block Incretin degradation
- Allows accumulation of GLP-1 by 2-3 fold
- Activate Glucose-Dependent Insulinotropic Polypeptides
- Stimulates beta cells to secrete Insulin
- Lowers Blood Sugar, but low risk of Hypoglycemia
- DPP-4 Inhibitors block Incretin degradation
- Differs from GLP1 Agonists
- Weight neutral
- No Nausea
V. Precautions
- DPP-4 Inhibitors are less than half as effective as lower cost medications (e.g. Metformin, Sulfonylureas)
- No longterm evidence of improved outcomes
- 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)
VI. Medications
- Sitagliptin (Januvia) tablets: 25 mg, 50 mg or 100 mg
- Combinations
- Janumet (Stagliptin and Metformin)
VII. Dosing
- May be dosed with or without food
- Sitagliptin 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
VIII. Adverse Effects
- Unless otherwise noted, adverse effects are for DPP-4 Inhibitor in general
-
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)
- Hepatotoxicity (Alogliptin, Vlidagliptin)
- Headache
- Bullous Pemphigoid
-
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)
IX. Safety
- Unknown safety in pregnancy (but generally avoided)
- Unknown safety in Lactation
X. Drug Interactions
- Fewer Drug Interactions than Saxagliptin (Onglyza) and Linagliptin (Tradjenta)
XI. Efficacy
- No longterm cardiovascular benefit (DPP-4 Inhibitor in general)
- Lowers HBA1C 0.5 to 0.9% with a mean 0.6% (DPP-4 Inhibitor in general)
- Contrast with Metformin, Sulfonylureas, GLP-1 Agonists, Pioglitazone lower A1C 1.0 to 1.5% at generic costs
- When combined with other hypoglycemics, its Glucose lowering effects are not additive
XII. Resources
XIII. References
Images: Related links to external sites (from Bing)
Related Studies
januvia (on 1/6/2022 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
JANUVIA 100 MG TABLET | $16.68 each | |
JANUVIA 25 MG TABLET | $16.66 each | |
JANUVIA 50 MG TABLET | $16.69 each |