Adult: Alogliptin 12.5 mg and metformin 500 mg tab
Alogliptin 12.5 mg and metformin 850 mg tab
Alogliptin 12.5 mg and metformin 1,000 mg tab
As an adjunct to diet and exercise or in combination with insulin or thiazolidinedione (e.g. pioglitazone): 1 tab bid. Initial dose must be individualised based on the patient's current regimen and may be adjusted according to effectiveness and tolerability. Max: 25 mg/2,000 mg daily.
Renal Impairment
Severe (eGFR <30 mL/min/1.73 m2): Contraindicated.
Hepatic Impairment
Contraindicated.
Administration
Should be taken with food.
Contraindications
Acute or chronic metabolic acidosis with or without coma (including diabetic ketoacidosis); diabetic pre-coma, alcoholism or acute alcohol intoxication, acute or chronic disease that may cause tissue hypoxia (e.g. cardiac or respiratory failure, recent MI); acute conditions that may alter renal function (e.g. severe infection, shock, dehydration). Hepatic and severe renal (eGFR <30 mL/min/1.73 m2) impairment.
Special Precautions
Patient with history of or risk factors for heart failure; history of pancreatitis; history of angioedema with another dipeptidyl peptidase-4 (DPP-4) inhibitor; or exposed to stress (e.g. infection, fever, trauma). Withhold treatment during surgical procedures. Consider discontinuing treatment prior to or at the time of iodinated contrast imaging procedure in patients with eGFR of 30-60 mL/min/1.73 m2 or history of hepatic impairment, alcoholism, or heart failure; re-evaluate eGFR 48 hours after the procedure and restart therapy if renal function is stable. Not intended for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis. Renal impairment (eGFR 30-60 mL/min/1.73 m2). Elderly. Pregnancy and lactation.
Adverse Reactions
Significant: Acute pancreatitis, bullous pemphigoid, severe and disabling arthralgia; heart failure, vitamin B12 deficiency; hypoglycaemia (particularly when used concomitantly with insulin or insulin secretagogues). Rarely, hypersensitivity reactions (e.g. anaphylaxis, angioedema, Stevens-Johnson syndrome, erythema multiforme). Gastrointestinal disorders: Diarrhoea, abdominal pain, GERD, gastroenteritis, vomiting, gastritis. Musculoskeletal and connective tissue disorders: Back pain. Nervous system disorders: Headache. Renal and urinary disorders: UTI. Respiratory, thoracic and mediastinal disorders: URTI, nasopharyngitis. Skin and subcutaneous tissue disorders: Pruritus, rash. Vascular disorders: Hypertension. Potentially Fatal: Lactic acidosis, hepatic failure.
Monitoring Parameters
Obtain plasma glucose (frequency depends on individual treatment regimen, hypoglycaemia risk, and other patient-specific factors) and HbA1c (at least twice annually for those with stable glycaemic control and meeting treatment goals; quarterly for those who have not met the treatment goals or with change in treatment). Monitor renal function (eGFR) and haematologic parameters (e.g. Hb/haematocrit, RBC indices) prior to initiation of therapy and periodically thereafter; hepatic function at baseline and as clinically indicated thereafter; and vitamin B12 serum concentrations every 1-2 years. Assess for signs and symptoms of heart failure, pancreatitis, metabolic acidosis, and hepatotoxicity.
Drug Interactions
Increased risk of hypoglycaemia with insulin or insulin secretagogues (e.g. sulfonylureas).
Metformin: Intravascular administration of iodinated contrast agents may cause acute decrease in renal function, leading to accumulation of metformin and increased risk of lactic acidosis. Organic cationic transporter-2 (OCT2)/multidrug and toxin extrusion (MATE) inhibitors (e.g. ranolazine, vandetanib, dolutegravir, cimetidine) may increase systemic exposure to metformin. Increased risk of lactic acidosis with carbonic anhydrase inhibitors (e.g. topiramate, zonisamide, acetazolamide, dichlorphenamide), ACE inhibitors, ARBs, and NSAIDs. Concomitant use with thiazides and other diuretics, corticosteroids, phenothiazines, oral contraceptives, estrogens, nicotinic acid, phenytoin, Ca channel blockers, isoniazid, sympathomimetics, and thyroid products may lead to loss of glycaemic control.
Food Interaction
Alcohol may increase the risk of lactic acidosis.
Action
Description: Mechanism of Action: Alogliptin inhibits the dipeptidyl peptidase-4 (DPP-4) enzyme, which is involved in the degradation of incretin hormones. Inhibition results in an increase in the levels of incretin hormones (e.g. glucagon-like peptide-1 [GLP-1] and glucose-dependent insulinotropic polypeptide [GIP]), thereby increasing insulin synthesis and release from pancreatic β cells and reducing glucagon secretion from pancreatic α cells leading to reduced hepatic glucose production.
Metformin is a biguanide antidiabetic agent that reduces hepatic glucose production by inhibiting gluconeogenesis and glycogenolysis. It also delays intestinal absorption of glucose and enhances insulin sensitivity by increasing peripheral glucose uptake and utilisation. Pharmacokinetics: Absorption: Alogliptin: Absorbed from the gastrointestinal tract. Bioavailability: Approx 100%. Time to peak plasma concentration: Approx 1-2 hours.
Metformin: Slowly and incompletely absorbed from the gastrointestinal tract. Absolute bioavailability: Approx 50-60% (fasting state). Time to peak plasma concentration: 2-3 hours. Distribution: Alogliptin: Plasma protein binding: 20-30%.
Metformin: Partitions into erythrocytes; concentrates in kidney, liver, and gastrointestinal tract. Crosses the placenta; enters breast milk (small amounts). Volume of distribution: 654 ± 358 L. Metabolism: Alogliptin: Minimally metabolised in the liver by CYP2D6 and CYP34A to active and inactive metabolites. Excretion: Alogliptin: Mainly via urine (76%; 60-71% as unchanged drug); faeces (13%). Terminal elimination half-life: Approx 21 hours.
Metformin: Via urine (90% as unchanged drug). Elimination half-life: 4-9 hours (plasma); approx 17.6 hours (blood).
Chemical Structure
Alogliptin Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 11450633, Alogliptin. https://pubchem.ncbi.nlm.nih.gov/compound/Alogliptin. Accessed Mar. 28, 2023.
Metformin Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 4091, Metformin. https://pubchem.ncbi.nlm.nih.gov/compound/Metformin. Accessed Feb. 27, 2023.
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