Adult: As an adjunct to diet and exercise to improve glycaemic control: Monotherapy or in combination with other antidiabetic agents: 100 mg once daily.
Renal Impairment
ESRD requiring haemodialysis or peritoneal dialysis: 25 mg once daily; may be given without regard to the timing of dialysis. eGFR <30 mL/min/1.73 m2: 25 mg once daily. eGFR ≥30 to <45 mL/min/1.73 m2: 50 mg once daily.
Administration
May be taken with or without food.
Contraindications
Hypersensitivity.
Special Precautions
Patient with history of pancreatitis, heart failure, or history of serious hypersensitivity reaction (e.g. angioedema) with other DPP-4 inhibitors. Patient undergoing periods of stress (e.g. trauma, infection, fever, surgery). Not indicated for use in patients with type 1 diabetes mellitus or diabetic ketoacidosis. Moderate to severe (eGFR <45 mL/min/1.73 m2) renal impairment, including ESRD requiring haemodialysis or peritoneal dialysis. Pregnancy and lactation.
Adverse Reactions
Significant: Hypoglycaemia (particularly in combination with sulfonylureas or insulins); worsening renal function, including acute renal failure (may require dialysis); severe and disabling arthralgia, bullous pemphigoid. Gastrointestinal disorders: Constipation, vomiting, mouth ulceration, stomatitis. Musculoskeletal and connective tissue disorders: Myalgia, back pain. Nervous system disorders: Headache, dizziness. Respiratory, thoracic and mediastinal disorders: Nasopharyngitis, upper respiratory tract infection, interstitial lung disease. Skin and subcutaneous tissue disorders: Rash, urticaria, pruritus. Potentially Fatal: Acute pancreatitis including haemorrhagic or necrotising pancreatitis, serious hypersensitivity reactions (e.g. anaphylaxis, angioedema, cutaneous vasculitis, exfoliative skin conditions including Stevens-Johnson syndrome).
This drug, particularly when taken in combination with other certain antidiabetics, may impair the patient's ability to concentrate and react due to hypoglycaemia; if affected, do not drive or operate machinery.
Monitoring Parameters
Obtain renal function before treatment initiation and periodically thereafter. Monitor HbA1c (at least twice yearly in patients with stable glycaemic control; quarterly in patients not meeting therapy goals or with changes in treatment); serum glucose. Assess for signs and symptoms of pancreatitis, heart failure, and hypersensitivity reactions; development of erosions or blisters.
Drug Interactions
Increased risk of hypoglycaemia when coadministered with sulfonylureas (e.g. glipizide, glimepiride) and insulins; consider lowering the dose of insulins or sulfonylureas. May slightly increase the serum concentration of digoxin.
Action
Description: Sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, improves glycaemic control by enhancing the levels and prolonging the effects of active incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). These hormones regulate glucose homeostasis and are rapidly inactivated by the DPP-4 enzyme. Both GLP-1 and GIP increase insulin synthesis and release from pancreatic β cells by intracellular signalling pathways involving cyclic AMP, while GLP-1 lowers glucagon secretion from pancreatic α cells resulting in lower hepatic glucose production. Sitagliptin prevents the hydrolysis of incretin hormones caused by DPP-4 enzyme, thereby increasing and prolonging active incretin levels that elevate insulin release and decrease glucagon concentrations in the circulation (glucose-dependent manner). Pharmacokinetics: Absorption: Rapidly absorbed from the gastrointestinal tract. Bioavailability: Approx 87%. Time to peak plasma concentration: 1-4 hours. Distribution: Volume of distribution: Approx 198 L. Plasma protein binding: 38%. Metabolism: Minimally metabolised primarily by CYP3A4, and to a lesser extent by CYP2C8 isoenzyme into inactive metabolites. Excretion: Mainly via urine (87%; approx 79% as unchanged drug, 16% as metabolites); faeces (13%). Terminal elimination half-life: Approx 12.4 hours.
Chemical Structure
Sitagliptin Source: National Center for Biotechnology Information. PubChem Database. Sitagliptin, CID=4369359, https://pubchem.ncbi.nlm.nih.gov/compound/Sitagliptin (accessed on Jan. 22, 2020)
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