Adult: Each tab contains sitagliptin and metformin (conventional: 50 mg/500 mg, 50 mg/1000 mg; extended-release: 50 mg/500 mg, 50 mg/1000 mg, 100 mg/1000 mg): Patients not currently treated w/ metformin: Initially, 100 mg/1000 mg daily. Patients currently treated w/ metformin: Initially, sitagliptin 100 mg and current daily metformin dose. Patients currently treated w/ metformin 1700 mg daily may receive 100 mg/2000 mg daily. Total daily doses are given in 2 divided doses (conventional) or once daily (extended-release). Max: Sitagliptin 100 mg/ and metformin 2000 mg daily.
Renal Impairment
Severe (GFR <30 mL/min): Contraindicated.
Hepatic Impairment
Contraindicated.
Administration
Should be taken with food.
Contraindications
Diabetic pre-coma, acute or chronic metabolic acidosis (e.g. diabetic ketoacidosis, lactic acidosis), alcoholism or acute alcohol intoxication, acute or chronic disease that may cause hypoxia (e.g. cardiac or resp failure, recent MI, shock), conditions which may alter renal function (e.g. severe infection, dehydration). Intravascular admin of iodinated contrast agents. Hepatic and severe renal impairment (GFR <30 mL/min). Lactation.
Special Precautions
Patient w/ CHF and those who are exposed to stress (e.g. infection, fever, trauma, surgery). Not intended for the treatment of diabetic ketoacidosis or type 1 DM. Renal impairment (GFR 30-45 mL/min). Pregnancy.
This drug may cause dizziness and somnolence, if affected, do not drive or operate machinery.
Monitoring Parameters
Monitor glycosylated Hb (HbA1c), serum glucose, hepatic and renal function, haematologic parameters prior to initiation of therapy and periodically thereafter.
Drug Interactions
Sitagliptin may increase risk of hypoglycaemia when used in combination w/ sulfonylureas or insulin. Increased risk of lactic acidosis w/ topiramate or other carbonic anhydrase inhibitors (e.g. zonisamide, acetazolamide, dichlorphenamide), NSAIDs, ACE inhibitors, angiotensin II receptor antagonists, diuretics. Concomitant cationic drugs that interfere w/ renal tubular transport systems (e.g. ranolazine, vandetanib, dolutegravir, cimetidine) may increase metformin levels. Thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, OCs, sympathomimetics, phenytoin, niacin, Ca channel blockers and isoniazid may produce hyperglycaemia which may lead to loss of glycaemic control. Metformin may impair vit B12 absorption. Potentially Fatal: Intravascular admin of iodinated contrast agents may cause renal dysfunction, leading to metformin-induced lactic acidosis.
Food Interaction
Food decreases the extent and slightly delays absorption of metformin. Alcohol may potentiate the effect of metformin on lactate metabolism.
Action
Description: Metformin is a biguanide antidiabetic agent that reduces hepatic glucose production by decreasing gluconeogenesis and glycogenolysis, decreases intestinal absorption of glucose and enhances insulin sensitivity by increasing peripheral utilisation and uptake of glucose. Sitagliptin inhibits dipeptidylpeptidase-4 (DPP-4), an enzyme that inactivates incretin hormones. Inhibition of DPP-4 results in an increase in the levels of incretin hormones [e.g. glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP)] which regulate glucose homeostasis by increasing insulin synthesis and release from pancreatic β-cells and decreasing glucagon secretion from pancreatic α-cells, leading to reduced hepatic glucose production. Pharmacokinetics: Absorption: Metformin: Slowly and incompletely absorbed from the GI tract. Absolute bioavailability: Approx 50-60%; reduced if taken w/ food. Time to peak plasma concentration: 2-3 hr (immediate-release); 4-8 hr (extended-release). Sitagliptin: Rapidly absorbed from the GI tract. Bioavailability: Approx 87%. Time to peak plasma concentration: Approx 1-4 hr. Distribution: Metformin: Partitions into erythrocytes; concentrates in kidney, liver, and GI tract. Crosses the placenta and enters breast milk (small amounts). Volume of distribution: 654 ±358 L. Sitagliptin: Volume of distribution: Approx 198 L. Plasma protein binding: 38%. Metabolism: Sitagliptin: Undergoes minimal metabolism, mainly by CYP3A4 enzyme and to a lesser extent by CYP2C8 enzyme to inactive metabolites. Excretion: Metformin: Via urine (90% as unchanged drug). Plasma elimination half-life: Approx 2-6 hr. Sitagliptin: Via urine (approx 79% as unchanged drug, 16% as metabolites) and faeces (13%). Elimination half-life: 12.4 hr.
Chemical Structure
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.
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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