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
- Linagliptin (Tradjenta) Tablets: 5 mg
- Combinations
- Trijardy XR (Linagliptin, Empagliflozin and Metformin XR)
VII. Dosing
- Linagliptin 5 mg orally daily
- No Renal Dosing required
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
- Significant CYP3A4 inducer and P-Glycoprotein Inducer
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
tradjenta (on 1/1/2023 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
TRADJENTA 5 MG TABLET | $16.80 each | |
trijardy xr (on 1/1/2023 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
TRIJARDY XR 10-5-1,000 MG TAB | $18.95 each | |
TRIJARDY XR 12.5-2.5-1,000 MG | $9.53 each | |
TRIJARDY XR 25-5-1,000 MG TAB | $18.87 each | |
TRIJARDY XR 5-2.5-1,000 MG TAB | $9.51 each |
Ontology: Linagliptin (C2746078)
Definition (NCI) | A potent, orally bioavailable dihydropurinedione-based inhibitor of dipeptidyl peptidase 4 (DPP-4), with hypoglycemic activity. The inhibition of DPP-4 by linagliptin appears to be longer lasting than that by some other DPP-4 inhibitors tested. |
Concepts | Organic Chemical (T109) , Pharmacologic Substance (T121) |
MSH | C568794 |
SnomedCT | 702798009, 703667006 |
English | 8-((3R)-3-Aminopiperidin-1-yl)-7-(but-2-yn-1-yl)-3-Methyl-1-((4-Methylquinazolin-2-yl)Methyl)-3,7-Dihydro-1H-Purine-2,6-Dione, (R)-8-(3-Amino-Piperidin-1-yl)-7-but-2-ynyl-3-Methyl-1-(4-methyl-quinazolin-2-ylmethyl)-3,7-dihydro-purine-2,6-dione, linagliptin, LINAGLIPTIN, Linagliptin, Linagliptin (substance), Linagliptin (product) |