Brand Name: DIASIT-M
Generic Name: Sitagliptin 50 mg + Metformin SR 500
Preparation: Bilayer tablet
Pharmacological Category: Antidiabitic
Mechanism of Action (MOA)
Sitagliptin inhibits dipeptidyl peptidase IV (DPP-IV) enzyme resulting in prolonged active incretin hormones level. Incretin hormones, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), regulate glucose homeostasis by increasing insulin synthesis and release from pancreatic beta cells and decreasing glucagon secretion from pancreatic alpha cells. Thus, Sitagliptin reduces blood glucose level.
Metformin decreases hepatic glucose production, decreasing intestinal absorption of glucose, and improves insulin sensitivity (increases peripheral glucose uptake and utilization).
Pharmacokinetics
Sitagliptin
Absorption: Rapidly from the gastrointestinal tract
Bioavailability: About 87%
Time to Peak: 1 to 4 hours
Protein Binding: 38%
Metabolism: Liver
Elimination Half-life: 12.4 hours
Excretion: 87% via urine and 13% via faeces
Metformin
Absorption: Slowly and incompletely from the gastrointestinal tract
Bioavailability: About 50 to 60%
Time to Peak: 4 to 8 hours (SR)
Protein Binding: Negligible
Metabolism: Not by liver
Elimination Half-life: About 2 to 6 hours
Excretion: Urine (unchanged)
Indication and Dosage
Type 2 Diabetes: 1 to 2 tablets daily
Dosing in renal Impairment
Estimated GFR (eGFR) > 45 mL/minute/1.73 m2: No dosage adjustment necessary; monitor renal function at least annually.
eGFR 30-45 mL/minute/1.73 m2: Use is not recommended; if eGFR falls to <45 mL/minute/1.73 m2 during therapy, consider benefits/risks of continuing therapy and limit to 1 tablet.
eGFR< 30 mL/minute/1.73 m2: Use is contraindicated.
Side Effects
1-10%: Diarrhoea, headache, upper respiratory tract infection, nausea, abdominal pain, vomiting
Frequency not defined: Exfoliative disorder of skin of scalp, Stevens-Johnson syndrome, anaphylaxis, Rhabdomyolysis, acute renal failure, angioedema, lactic acidosis (Rare)
Postmarketing reports: Hypersensitivity reactions including anaphylaxis, angioedema, rash, urticaria, cutaneous vasculitis, and exfoliative skin conditions including Stevens-Johnson syndrome; upper respiratory tract infection; hepatic enzyme elevations; acute pancreatitis including fatal and nonfatal hemorrhagic and necrotizing pancreatitis; constipation; vomiting; headache; worsening renal function including acute renal failure sometimes requiring dialysis; myalgia; pain in extremity; back pain; severe disabling arthralgia; pruritus; mouth ulceration, and stomatitis
Contraindications
Hypersensitivity including anaphylaxis or angioedema, severe renal disease (eGFR< 30 ml/min/1.73 m2), acute/chronic metabolic acidosis including diabetic ketoacidosis
Warnings/ Precautions
• Risk of lactic acidosis with metformin accumulation.
• Initiate in patients greater than 80 years only if CrCl indicates no reduction in renal function.
• Avoid excessive alcohol use.
• Withhold in presence of any condition associated with hypoxemia, dehydration, or sepsis.
• Discontinue temporarily prior to any intravascular radiocontrast study with iodine containing material and for any surgical procedure.
• Risk of hypoglycemia especially in elderly, debilitated or malnourished, adrenal/pituitary insufficiency, strenuous exercise not compensated by caloric intake, heavy alcohol use, hepatic/renal impairment, beta blockers.
• May cause acute pancreatitis including hemorrhagic and necrotizing pancreatitis.
• Angioedema reported with other DPP-4 inhibitors; caution with history of angioedema.
• Severe and disabling arthralgia reported in patients taking DPP-4 inhibitors; consider as possible cause for severe joint pain and discontinue drug if appropriate.
• Monitor renal function of the elderly closely; withhold the therapy promptly in presence of any condition associated with hypoxemia, dehydration, or sepsis.
• Discontinue at the time of or before an iodinated contrast imaging procedure in patients with an eGFR between 30-60 mL/minute/1.73 m2; in patients with a history of liver disease, alcoholism, heart failure, or in patients who will be administered intra-arterial iodinate contrast.
Drug Interactions
• Alcohol may increase the risk of lactic acidosis as well as of hypoglycemia.
• May enhance the adverse/toxic effect of ACE inhibitors.
• Alpha-lipoic acid may enhance the hypoglycemic effect.
• Androgens, MAO inhibitors, salicylates, and SSRIs may enhance the hypoglycemic effect.
• May increase the serum concentration of digoxin.
• May enhance the hypoglycemic effect of insulin and sulfonylureas.
• Thiazide and thiazide-like diuretics may diminish the therapeutic effect.
Pregnancy Category: B
Presentation
DIASIT-M: 10 X 10’s
