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
- Saxagliptin (Onglyza) tablets: 2.5, 5 mg
VII. Dosing
- Saxagliptin 2.5 to 5 mg/day
- Adjust for renal Impairment
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
- Higher risk with pre-existing CHF and renal Impairment
- 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
- Significant CYP3A4 Drug Interactions
- Decrease Saxagliptin dose with strong CYP3A4 Inhibitors (e.g. Ketoconazole)
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
saxagliptin (on 10/18/2023 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
SAXAGLIPTIN HCL 5 MG TABLET | Generic | $1.63 each |
onglyza (on 1/1/2022 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
ONGLYZA 2.5 MG TABLET | $15.07 each | |
ONGLYZA 5 MG TABLET | $15.07 each |
Ontology: saxagliptin (C1611934)
Definition (NCI) | A potent, selective and competitive, cyanopyrrolidine-based, orally bioavailable inhibitor of dipeptidyl peptidase 4 (DPP-4), with hypoglycemic activity. Saxagliptin is metabolized into an, although less potent, active mono-hydroxy metabolite. |
Concepts | Pharmacologic Substance (T121) , Amino Acid, Peptide, or Protein (T116) |
MSH | C502994 |
SnomedCT | 443087004, 443066009 |
English | SAXAGLIPTIN, Saxagliptin (substance), Saxagliptin, Saxagliptin (product), (1S,3S,5S)-2-((2S)-2-Amino-2-(3-hydroxyadamantan-1-yl) acetyl)-2-azabicyclo(3.1.0)hexane-3-carbonitrile hydrate, saxagliptin, 3-hydroxyadamantylglycine-4,5-methanoprolinenitrile hydrate |
Spanish | saxagliptina (sustancia), saxagliptina (producto), saxagliptina |