Vipidia

Indications

• Type 2 diabetes mellitus
• Management of hyperglycemia in conjunction with diet and exercise

Dosage

Children: The safety and efficacy of alogliptin in children and adolescents have not been established; therefore, it is not recommended for use in this population.

Adults: The recommended dose of alogliptin is 25 mg once daily. In patients with moderate to severe renal impairment, the dose should be reduced to 12.5 mg once daily.

Mechanism of action

Alogliptin inhibits dipeptidyl peptidase 4 (DPP-4), an enzyme that degrades incretin hormones such as glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). By inhibiting DPP-4, alogliptin increases the levels of active incretins in the bloodstream, which enhances insulin secretion from pancreatic beta cells and suppresses glucagon secretion from alpha cells, leading to reduced hepatic glucose production and improved glycemic control.

Pharmacodynamics

Peak inhibition of DPP-4 occurs within 2-3 hours after administration, exceeding 93% across various doses. Inhibition remains above 80% for 24 hours at doses of 25 mg or higher. Alogliptin also reduces postprandial glucagon levels while increasing active GLP-1 levels after meals. It has no significant effect on the QTc interval.

Pharmacokinetics

Alogliptin is rapidly absorbed following oral administration, with peak plasma concentrations reached within 1-2 hours. It has a bioavailability of approximately 100% and is primarily eliminated via the kidneys. The half-life of alogliptin is about 21 hours, allowing for once-daily dosing. It is minimally metabolized by the liver, which reduces the potential for drug-drug interactions.

Contra-indications

• Hypersensitivity to alogliptin or any component of the formulation
• History of pancreatitis
• Severe renal impairment (eGFR < 15 mL/min)

Adverse effects

• Hypoglycemia (particularly in combination with other antidiabetic agents)
• Gastrointestinal disturbances (nausea, vomiting, diarrhea)
• Headache
• Peripheral edema
• Possible risk of pancreatitis
• Hypersensitivity reactions (including angioedema and anaphylaxis)

Interactions

• Concomitant use with sulfonylureas or insulin may increase the risk of hypoglycemia
• Caution advised with other medications affecting glucose metabolism
• May alter the pharmacokinetics of other drugs metabolized by CYP450 enzymes

Precautions

• Monitor renal function regularly, especially in elderly patients
• Caution in patients with a history of heart failure
• Assess for signs of pancreatitis during treatment
• Use with caution in patients with hepatic impairment

Pregnancy

There are no adequate and well-controlled studies in pregnant women. Alogliptin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether alogliptin is excreted in human milk. Caution should be exercised when alogliptin is administered to a nursing woman.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Alogliptin 6.25 mg tablets
• Alogliptin 12.5 mg tablets
• Alogliptin 25 mg tablets
• Combination formulations with metformin

Mechanism of action

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. 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.

Pharmacodynamics

Peak inhibition of DPP-4 occurs within 2-3 hours after a single-dose administration to healthy subjects. 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.