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Initial therapy in type 2 DM to improve glycemic control when diet & exercise do not provide adequate glycemic control. Adjunct to diet & exercise to improve glycemic control in type 2 DM in combination w/ insulin; inadequately controlled on metformin or sitagliptin alone, or in patients already being treated w/ sitagliptin & metformin combination; as part of triple combination therapy in combination w/ sulfonylurea or PPARγ agonist (eg, thiazolidinediones).

Individualized dosage not exceeding max recommended daily dose of sitagliptin 100 mg. Patient w/ type 2 DM, whose hyperglycemia is inadequately controlled w/ diet & exercise alone Initially sitagliptin 50 mg/metformin HCl 500 mg bid. May be titrated up to sitagliptin 50 mg/metformin HCl 1,000 mg bid. Patients inadequately controlled on metformin monotherapy Usual starting dose: Sitagliptin 50 mg bid + metformin dose already being taken. Patients inadequately controlled on sitagliptin monotherapy Usual starting dose: Sitagliptin 50 mg/metformin HCl 500 mg bid. May be titrated up to sitagliptin 50 mg/metformin HCl 1,000 mg bid. Patients switching from co-administration of sitagliptin & metformin May be initiated at dose of sitagliptin & metformin already being taken. Patients inadequately controlled on dual combination therapy w/ any 2 of the following antihyperglycemic agents: Sitagliptin, metformin or sulfonylurea, or PPARγ agonist, or insulin Usual starting dose: Sitagliptin 50 mg bid. Determine starting dose of metformin based on glycemic control level & current metformin dose.

Should be taken with food.

Hypersensitivity. Diabetic ketoacidosis w/ or w/o coma & metabolic acidosis. Renal failure or severe renal impairment.

Discontinue use if hypersensitivity (eg, anaphylaxis, urticaria, angioedema, exfoliative dermatitis or other serious skin conditions including SJS), bullous pemphigoid, pancreatitis, severe, disabling arthralgia are suspected; at the time of, or prior to radiographic contrast administration w/ eGFR between 30-60 mL/min/1.73 m²; in patients w/ history of liver disease, alcoholism or heart failure; who will be administered intra-arterial iodinated contrast, re-evaluate eGFR 48 hr after the procedure. Not to be used in the treatment of type 1 DM; patients w/ diabetic ketoacidosis, severe infection or serious accident; patients w/ alcoholism. Promptly withhold in the presence of conditions associated w/ hypoxemia, dehydration or sepsis. Temporarily suspend treatment for any surgery, except for minor procedures where fluid & food intake is not restricted. Suspect lactic acidosis in diabetic patient w/ metabolic acidosis lacking evidence of ketoacidosis (ketonuria & ketonemia). Patient w/ history of angioedema or anaphylaxis to another dipeptidyl peptidase-4 inhibitor; or increased risk factors for heart failure, including patients w/ existing cardiac disease or kidney disease; CHF; vit B₁₂ deficiency or vit B₁₂-dependent anemia. Carefully monitor patients w/ diarrhea, gastroparesis, GI obstruction, ileus or vomiting. Annual measurement of hematologic parameters in patients on chronic treatment. Debilitated or malnourished patients, & w/ adrenal or pituitary insufficiency or hypothyroidism. Take into account dizziness & somnolence when driving or using machines. Assess renal function prior to initiation of therapy & at least annually thereafter. Avoid in patients w/ hepatic disease. Not recommended in patients w/ eGFR ≥30 & <45 mL/min/1.73 m². Risk of conception in premenopausal anovulatory females w/ insulin resistance (eg, PCOS) if contraception is used inadequately. Not to be used during pregnancy & breast-feeding. Childn <18 yr. Elderly w/ renal impairment.

Hypoglycemia; decrease levels of vit B₁₂ w/o clinical manifestations & rarely associated w/ anemia; diarrhea, nausea, flatulence, vomiting; headache; URTI, nasopharyngitis, pharyngolaryngeal pain, bronchitis, sinusitis, flu; arthralgia; peripheral edema. Metformin: Abdominal pain, loss of appetite. Metallic taste.

Concomitant use w/ iodinated contrast agents. Increased risk of lactic acidosis w/ alcohol, NSAIDs (including COX II inhibitors), ACE inhibitors, AIIA, diuretics (especially loop diuretics). Increased systemic exposure & risk for lactic acidosis w/ drugs that interfere w/ common renal tubular transport systems involved in the renal elimination of metformin (eg, organic cationic transporter-2/multidrug & toxin extrusion inhibitors eg, ranolazine, vandetanib, dolutegravir, & cimetidine). Concomitant use w/ glucocorticoids, β2 agonist, & diuretics due to their intrinsic hyperglycaemic activity. Decreased blood glucose level w/ ACE inhibitors. Sitagliptin: Inhibition of organic anion transporter-3 mediated transport w/ probenecid. Increased AUC & C_max w/ ciclosporin. Increased AUC & C_max of digoxin.

Antidiabetic Agents

A10BD07 - metformin and sitagliptin ; Belongs to the class of combinations of oral blood glucose lowering drugs. Used in the treatment of diabetes.

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