Alogliptin

Generic Name

Alogliptin

Brand Names

Nesina

Vipidia (Europe)

Alogliptin generics are available in some countries

Drug Class

Dipeptidyl Peptidase-4 (DPP-4) Inhibitor

Oral antihyperglycemic agent

Incretin-based therapy

Mechanism of Action

Alogliptin selectively inhibits the enzyme dipeptidyl peptidase-4 (DPP-4), which is responsible for the rapid degradation of incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP)

By inhibiting DPP-4, alogliptin increases the levels of these active incretin hormones, which in turn enhances glucose-dependent insulin secretion from pancreatic beta-cells and suppresses inappropriate glucagon secretion from alpha-cells

This leads to improved glycemic control through a glucose-dependent mechanism, thus reducing the risk of hypoglycemia

Indications

Indicated for the treatment of adults with type 2 diabetes mellitus to improve glycemic control as an adjunct to diet and exercise

Used as monotherapy or in combination with other antihyperglycemic agents including:

Metformin

Sulfonylureas

Thiazolidinediones

Insulin

Dosage and Administration

Standard dose: 25 mg orally once daily with or without food

Renal impairment:

Mild (CrCl ≥60 mL/min): 25 mg once daily

Moderate (CrCl ≥30 to <60 mL/min): 12.5 mg once daily

Severe (CrCl ≥15 to <30 mL/min) or end-stage renal disease (on dialysis): 6.25 mg once daily

No dose adjustment required in hepatic impairment (but use caution in moderate to severe cases)

Can be taken at any time of day consistently

Pharmacokinetics

Oral bioavailability: ~100%

Time to peak plasma concentration: 1 to 2 hours

Half-life: 21 hours

Protein binding: ~20%

Primarily excreted unchanged in the urine (76%)

Limited hepatic metabolism via CYP2D6 and CYP3A4 (minimal impact)

Contraindications

Hypersensitivity to alogliptin or any component of the formulation

History of serious hypersensitivity reactions including anaphylaxis, angioedema, or Stevens-Johnson syndrome to any DPP-4 inhibitor

Precautions

Use with caution in patients with a history of pancreatitis

Use with caution in moderate to severe hepatic impairment

Adjust dose in renal impairment

Monitor for signs of heart failure when used in combination with thiazolidinediones or in patients with pre-existing heart disease

Discontinue if serious skin reactions occur

Adverse Effects

Common

Headache

Nasopharyngitis

Upper respiratory tract infection

Back pain

Less Common

Abdominal pain

Gastroenteritis

Elevated hepatic enzymes

Pruritus

Rash

Serious

Acute pancreatitis

Severe hypersensitivity reactions (including anaphylaxis, angioedema, and exfoliative skin conditions)

Hepatotoxicity

Heart failure (when used with pioglitazone or in susceptible patients)

Bullous pemphigoid

Arthralgia

Pregnancy and Lactation

Pregnancy

Limited data available

Animal studies did not show teratogenicity at clinically relevant doses

Use only if potential benefit justifies potential risk to fetus

Lactation

Unknown if excreted in human milk

Excreted in animal milk

Use caution or consider alternative if breastfeeding

Use in Special Populations

Geriatric

No dose adjustment based on age alone

Increased sensitivity in older adults possible due to comorbidities or polypharmacy

Renal Impairment

Dose adjustment required

Routine monitoring of renal function recommended before initiation and periodically during treatment

Hepatic Impairment

No dose adjustment required for mild impairment

Limited data in moderate to severe hepatic impairment – use with caution

Drug Interactions

Digoxin

Slight increase in digoxin levels may occur

Monitor serum digoxin if clinically indicated

Other Hypoglycemics (e.g., insulin, sulfonylureas)

Increased risk of hypoglycemia

Dose adjustment of the concomitant agent may be necessary

CYP450 Substrates

Minimal involvement with CYP pathways

Low risk of clinically significant interactions

ACE Inhibitors and ARBs

May slightly increase the risk of angioedema when used with DPP-4 inhibitors

Monitor for allergic reactions

Monitoring Parameters

Fasting and postprandial blood glucose levels

Hemoglobin A1c every 3 months

Renal function before starting and periodically

Signs of pancreatitis (persistent severe abdominal pain, nausea, vomiting)

Signs of hypersensitivity or rash

Signs of heart failure if used in patients at risk

Advantages

Once-daily oral dosing

Low risk of hypoglycemia when used alone

Weight neutral

Can be combined with multiple classes of antihyperglycemics

Suitable for patients intolerant to metformin

Limitations

Modest HbA1c reduction compared to other agents

Ineffective in type 1 diabetes or diabetic ketoacidosis

Increased caution required in renal or hepatic dysfunction

Cost considerations compared to generic alternatives

Not studied in pediatric populations

Formulations

Alogliptin tablets: 6.25 mg, 12.5 mg, 25 mg

Available as monotherapy or in fixed-dose combinations with:

Metformin (Kazano)

Pioglitazone (Oseni)

Patient Counseling Points

Take once daily at the same time each day

Can be taken with or without food

Do not double dose if one is missed

Report any unexplained abdominal pain, skin rash, or shortness of breath

Adhere to dietary and lifestyle recommendations alongside pharmacologic therapy

Inform healthcare provider of all medications including over-the-counter products and supplements

Continue regular monitoring of blood sugar and kidney function as advised by your doctor