Pharm
Linagliptin
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Linagliptin
, Tradjenta, Trijardy XR
See Also
DPP-4 Inhibitor
Incretin Mimetic
Type II Diabetes Medications
Sitagliptin
Saxagliptin
Alogliptin
Indications
Type II Diabetes Mellitus
Insulin
deficiency and
Insulin Resistance
Adjunct to
Glucophage
,
Sulfonylurea
s,
Glitazone
s
Contraindications
Type I Diabetes Mellitus
Congestive Heart Failure
Prior history of malignancy
Due to increased risk of cancer invasion and metastases
Mechanism
See
DPP-4 Inhibitor
Dipeptidyl Peptidase-4 (
DPP-4
) is an enzyme that degrades the
Incretin
s
GLP-1
and GLP-2
Incretin
s (GIP and GLP1) are normally released from
GI Tract
(enteroendocrine cells) following meals
Incretin
s increase
Glucose
dependent
Insulin
secretion, and inhibit
Glucagon
secretion
DPP4 Inhibitor Activity
DPP-4 Inhibitor
s block
Incretin
degradation
Allows accumulation of
GLP-1
by 2-3 fold
Activate
Glucose
-Dependent
Insulin
otropic Polypeptides
Stimulates beta cells to secrete
Insulin
Lowers
Blood Sugar
, but low risk of
Hypoglycemia
Differs from
GLP1 Agonist
s
Weight neutral
No
Nausea
Precautions
DPP-4 Inhibitor
s are less than half as effective as lower cost medications (e.g.
Metformin
,
Sulfonylurea
s)
No longterm evidence of improved outcomes
Decrease dose in renal
Impairment
May consider for those close to goal AND
Already either on other
Oral Hypoglycemic
s or in whom they are contraindicated (e.g.
Chronic Kidney Disease
)
Medications
Linagliptin (Tradjenta) Tablets: 5 mg
Combinations
Trijardy XR (Linagliptin,
Empagliflozin
and
Metformin
XR)
Dosing
Linagliptin 5 mg orally daily
No
Renal Dosing
required
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
)
Anaphylaxis
Angioedema
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)
Stop agent if suspect
Gliptin
-induced pain (and avoid other
Gliptin
s)
Consider other possible causes (e.g.
Statin
induced
Myopathy
)
FDA Alert
http://www.fda.gov/drugs/drugsafety/ucm459579.htm
Safety
Unknown safety in pregnancy (but generally avoided)
Unknown safety in
Lactation
Drug Interactions
Significant
CYP3A4
inducer and
P-Glycoprotein Inducer
Efficacy
No longterm cardiovascular benefit (
DPP-4 Inhibitor
in general)
Green (2015) N Engl J Med 373(3): 232-42 [PubMed]
Scirica (2013) N Engl J Med 369(14): 1317-26 [PubMed]
White (2013) N Engl J Med 369(14): 1327-35 [PubMed]
Lowers
HBA1C
0.5 to 0.9% with a mean 0.6% (
DPP-4 Inhibitor
in general)
Contrast with
Metformin
,
Sulfonylurea
s,
GLP-1 Agonist
s,
Pioglitazone
lower A1C 1.0 to 1.5% at generic costs
When combined with other hypoglycemics, its
Glucose
lowering effects are not additive
Resources
Linagliptin (DailyMed)
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c797ea5c-cab7-494b-9044-27eba0cfe40f
References
(2013) Presc Lett 20(8):46
Jones (2007) Am Fam Physician 75:1831-5 [PubMed]
Steinberg (2019) Am Fam Physician 99(4): 237-43 [PubMed]
Vaughan (2024) Am Fam Physician 109(4): 333-42 [PubMed]
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