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Alogliptin; Uses, Dosage, Side Effects, Drug Interactions

Alogliptin is a selective, orally bioavailable, pyrimidinedione-based inhibitor of dipeptidyl peptidase 4 (DPP-4), with hypoglycemic activity. In addition to its effect on glucose levels, alogliptin may inhibit inflammatory responses by preventing the toll-like receptor 4 (TLR-4)-mediated formation of proinflammatory cytokines.

Alogliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor which is used in combination with diet and exercise in the therapy of type 2 diabetes, either alone or in combination with other oral hypoglycemic agents. Alogliptin has been reported to cause liver injury, but the characteristics and details of the injury have not been defined in the published literature.

Alogliptin is a selective, orally available inhibitor of dipeptidyl peptidase-4 being developed by Takeda Global Research & Development Center, Inc. as a treatment for type 2 diabetes mellitus. Inhibition of dipeptidyl peptidase-4 (DPP-4) prolongs the action of 2 important incretin hormones, glucagon-like peptide-1 (GLP-1). Like other members of the gliptin class, it causes little or no weight gain, exhibits relatively little risk of causing hypoglycemia, and exhibits relatively modest glucose-lowering activity. Alogliptin and other gliptins are commonly used in combination with metformin in patients whose diabetes cannot adequately be controlled with metformin alone.

Mechanism of Action of Alogliptin

Alogliptin inhibits dipeptidyl peptidase 4 (DPP-4), which normally degrades the incretins glucose-dependent insulinotropic polypeptide (GIP) and glucagon like peptide 1 ( GLP-1). The inhibition of DPP-4 increases the amount of active plasma incretins which helps with glycemic control. GIP and GLP-1 stimulate glucose dependent secretion of insulin in pancreatic beta cells. GLP-1 has the additional effects of suppressing glucose dependent glucagon secretion, inducing satiety, reducing food intake, and reducing gastric emptying.The peak inhibition of DPP-4 exceeded 93% across doses of 12.5 mg to 800 mg. Inhibition of DPP-4 remained above 80% at 24 hours for doses greater than or equal to 25 mg. Alogliptin also demonstrated decreases in postprandial glucagon while increasing postprandial active GLP-1 levels compared to placebo over an 8-hour period following a standardized meal. Alogliptin does not affect the QTc interval.

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Increased concentrations of the incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released into the bloodstream from the small intestine in response to meals. These hormones cause insulin release from the pancreatic beta cells in a glucose-dependent manner but are inactivated by the DPP-4 enzyme within minutes. GLP-1 also lowers glucagon secretion from pancreatic alpha cells, reducing hepatic glucose production. In patients with type 2 diabetes, concentrations of GLP-1 are reduced but the insulin response to GLP-1 is preserved. Alogliptin is a DPP-4 inhibitor that slows the inactivation of the incretin hormones, thereby increasing their bloodstream concentrations and reducing fasting and postprandial glucose concentrations in a glucose-dependent manner in patients with type 2 diabetes mellitus. Alogliptin selectively binds to and inhibits DPP-4 but not DPP-8 or DPP-9 activity in vitro at concentrations approximating therapeutic exposures.

Indications of Alogliptin

Type 2 Diabetes Mellitus
Alogliptin is a dipeptidyl peptidase-4 inhibitor
Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
Indicated in adults aged 18 years and older with type 2 diabetes mellitus to improve glycaemic control in combination with other glucose-lowering medicinal products including insulin, when these, together with diet and exercise, do not provide adequate glycaemic control

Contra-Indications of Alogliptin

Low blood sugar
Chronic Heart Failure
Acute Inflammation of the Pancreas
Abnormal Liver Function Tests
Moderate to Severe Kidney Impairment
Allergies to gliptins (DPP-4 Inhibitors) & benzoate Analogues

Dosage of Alogliptin

Strengths: 6.25 mg; 12.5 mg; 25 mg

Diabetes Type 2

Usual dose: 25 mg orally once a day

Side Effects of Alogliptin

Most common

physical weakness (asthenia)
diarrhea
gas (flatulence)
symptoms of weakness, muscle pain (myalgia)
upper respiratory tract infection
low blood sugar (hypoglycemia)
abdominal pain (GI complaints), lactic acidosis (rare)
low blood levels of vitamin B-12
nausea,vomiting
chest discomfort
chills, dizziness
bloating/abdominal distention
constipation
heartburn

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More common

Abdominal or stomach discomfort
cough or hoarseness
decreased appetite
diarrhea
fast or shallow breathing
fever or chills
general feeling of discomfort
lower back or side pain
muscle pain or cramping
painful or difficult urination

Less common

Abnormal stools
bad, unusual, or unpleasant (after) taste
change in taste
difficulty with moving
discoloration of the fingernails or toenails
flu-like symptoms
joint pain
rash
runny nose
sneezing
stuffy nose
swollen joints

Drug Interactions of Alogliptin

Alogliptin may interact with following drugs, supplements & may decrease the efficacy of the drug

angiotensin-converting enzyme inhibitors (ACEIs; captopril, ,ramipril)
alcohol
beta-blockers
cough and cold products containing decongestants
antipsychotic medications (e.g., chlorpromazine, haloperidol, olanzapine,
birth control pills
bupropion
corticosteroids (e.g., dexamethasone, prednisone)
diabetic drugs (e.g., glyburide, insulin, repaglinide, sitagliptin)
diuretics (e.g., furosemide, hydrochlorothiazide)
phenytoin
quinolone antibiotics (e.g., levofloxacin, moxifloxacin)
ranitidine
thyroid medicines such as levothyroxine
trimethoprim
selective serotonin reuptake inhibitors (SSRIs; citalopram, fluoxetine, sertraline paroxetine,
verapamil
warfarin

Pregnancy & Lactation

FDA Pregnancy Category B

Pregnancy

This medication should not be used during pregnancy unless the benefits outweigh the risks. If you become pregnant while taking this medication, contact your doctor immediately.

Lactation

It is not known if alogliptin passes into breast milk. If you are a breastfeeding mother and are taking this medication, it may affect your baby. Talk to your doctor about whether you should continue breastfeeding.