Aglip12.5 mg

Aglip is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

• Established/FDA-approved use: Monotherapy or combination therapy (with metformin, a sulfonylurea, pioglitazone, or insulin) for glycemic control in type 2 diabetes.
• Guideline-supported use: As an add-on option when metformin alone is insufficient, particularly in patients where hypoglycemia or weight gain are concerns.
• Not indicated for: Type 1 diabetes mellitus or diabetic ketoacidosis (see Contraindications).

Aglip is not a substitute for insulin in patients who require insulin and should not be used to treat diabetic ketoacidosis.

Each film-coated tablet contains Alogliptin (as alogliptin benzoate) in strengths of 6.25 mg, 12.5 mg, or 25 mg, along with pharmaceutically inert excipients such as mannitol, microcrystalline cellulose, hydroxypropyl cellulose, croscarmellose sodium, magnesium stearate, and a film-coating system.

Aglip is an orally active, highly selective inhibitor of the dipeptidyl peptidase-4 (DPP-4) enzyme, belonging to the "gliptin" class of oral antidiabetic agents. It is used in the management of type 2 diabetes mellitus to help lower blood glucose levels by enhancing the body's own incretin-based insulin response.

Aglip is available as an immediate-release film-coated tablet for once-daily oral administration, either alone or in fixed-dose combination with metformin or pioglitazone.

Aglip belongs to the Dipeptidyl Peptidase-4 (DPP-4) inhibitor class of oral antidiabetic drugs, commonly known as "gliptins."

Mechanism of Action

Alogliptin selectively inhibits the DPP-4 enzyme, which is responsible for the rapid degradation of the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). By slowing incretin inactivation, Alogliptin increases circulating levels of active GLP-1 and GIP, which in turn increases glucose-dependent insulin secretion from pancreatic beta cells and decreases inappropriate glucagon secretion from alpha cells.

Pharmacokinetics

• Absorption: Rapidly absorbed with peak plasma concentration reached in about 1-2 hours; absolute bioavailability approximately 100%.
• Metabolism: Minimally metabolized; the majority of a dose is excreted unchanged, with minor metabolism via CYP2D6 and CYP3A4.
• Elimination: Primarily renal (about 76% recovered in urine as unchanged drug); elimination half-life is approximately 21 hours, supporting once-daily dosing.

Aglip tablets should be swallowed whole with a glass of water, with or without food, at approximately the same time each day to maintain consistent blood levels. Do not crush or split the tablet unless advised by a physician.

Aglip has a low potential for clinically significant drug interactions because it is minimally metabolized by the cytochrome P450 system. The main clinically important interaction is:

• Sulfonylureas and insulin: Combining Aglip with insulin secretagogues (sulfonylureas) or insulin increases the risk of hypoglycemia. A lower dose of the sulfonylurea or insulin may be needed when co-administered with Aglip.

No dose adjustment of Aglip is required when co-administered with metformin, pioglitazone, warfarin, or digoxin based on available pharmacokinetic studies. Always inform the prescribing physician of all other medications being taken.

Most patients tolerate Aglip well. Reported adverse effects include:

• Common: Nasopharyngitis, upper respiratory tract infection, headache.
• Less common: Hypoglycemia (mainly when combined with sulfonylureas or insulin), mild gastrointestinal upset.
• Rare but serious: Acute pancreatitis, severe hypersensitivity reactions, severe and disabling joint pain, hepatic failure, bullous pemphigoid, and heart failure/worsening heart failure (see Precautions and Warnings for details on each).

Pregnancy: Data on the use of Aglip in pregnant women are limited. Because uncontrolled hyperglycemia in pregnancy is associated with adverse maternal and fetal outcomes, and insulin is generally the preferred agent for glycemic control during pregnancy, Aglip should be used in pregnancy only if clearly needed and if the potential benefit justifies the potential risk to the fetus; consult a physician before use.

Lactation: It is not known whether Aglip is excreted in human breast milk. Because many drugs are excreted in breast milk and the effect on a nursing infant is unknown, a decision should be made whether to discontinue nursing or discontinue Aglip, taking into account the importance of the drug to the mother; consult a physician.

• Heart failure: Post-marketing surveillance has reported increased risk of hospitalization for heart failure with Aglip. Monitor for signs and symptoms of heart failure (unusual shortness of breath, rapid weight gain, swelling) and consider discontinuation if heart failure develops.
• Acute pancreatitis: Cases of acute pancreatitis, including fatal cases, have been reported. Discontinue Aglip promptly if pancreatitis is suspected (persistent severe abdominal pain).
• Severe and disabling joint pain: A rare but serious class effect of DPP-4 inhibitors; can occur at any time and may be severe and disabling. Discontinue Aglip if severe arthralgia develops and evaluate for alternative causes.
• Hepatic effects: Rare postmarketing reports of hepatic failure, sometimes fatal, have occurred. Monitor liver function periodically; discontinue Aglip if hepatic injury is suspected.
• Renal impairment: Dose adjustment is required based on renal function (see Dosage and Administration); assess renal function before starting and periodically thereafter.
• Bullous pemphigoid: Rare skin reactions requiring hospitalization have been reported; discontinue Aglip if bullous pemphigoid is suspected and refer to a dermatologist.
• Hypoglycemia: Risk increases when Aglip is combined with a sulfonylurea or insulin (see Interactions).

There is limited clinical experience with Aglip overdose. In case of a suspected overdose, seek immediate medical attention or contact a poison control center/emergency services right away. Management should include general supportive measures (monitoring vital signs, blood glucose, and clinical status) as clinically indicated; Aglip is dialyzable to a modest extent, and hemodialysis may be considered in severe cases under medical supervision. Do not attempt to manage an overdose at home without professional medical guidance.

Store at room temperature (below 30°C), away from light and moisture. Keep out of reach of children.

• Renal impairment: Dose reduction of Aglip is required in moderate and severe renal impairment and end-stage renal disease (see Dosage and Administration).
• Hepatic impairment: No dose adjustment is needed in mild to moderate hepatic impairment; Aglip is not recommended in patients with severe hepatic impairment due to limited data.
• Elderly: No overall dose adjustment is required based on age alone, but elderly patients often have reduced renal function, so renal function should be assessed.
• Pediatric patients: Safety and efficacy of Aglip have not been established in patients under 18 years of age (see Pediatric Uses).
• Pregnancy and lactation: See Pregnancy and Lactation section.

Aglip is generally used as a long-term, chronic therapy for the management of type 2 diabetes, continued for as long as it remains effective and well tolerated as determined by periodic assessment of glycemic control (e.g., HbA1c) by the treating physician. It is not intended for short-term or as-needed use. Do not stop Aglip abruptly without medical advice, as this may worsen glycemic control.

Alogliptin is classified as a Dipeptidyl Peptidase-4 (DPP-4) inhibitor, an oral antihyperglycemic (antidiabetic) agent, also referred to as an incretin-enhancer or "gliptin."

Alogliptin works by selectively and competitively inhibiting the DPP-4 enzyme, which normally rapidly breaks down the incretin hormones GLP-1 and GIP after they are released from the gut in response to meals. By inhibiting DPP-4, Alogliptin prolongs the activity of these incretins, resulting in increased glucose-dependent insulin secretion and decreased glucagon secretion, which together lower blood glucose without a high inherent risk of hypoglycemia when used alone.

B

The safety and efficacy of Aglip have not been established in pediatric patients (under 18 years of age). Aglip is therefore not recommended for use in children and adolescents outside of a clinical trial setting, and should only be considered under specialist supervision if no suitable alternative exists.