Generic Name

Metformin Hydrochloride + Sitagliptin

Precaution

Not for use in type 1 DM or treatment of ketoacidosis. Discontinue use if pancreatitis is suspected. Renal & hepatic impairment. Sulfonylurea- or insulin-induced hypoglycemia, risk of lactic acidosis, hypoxic states, surgical procedures, alcohol intake, decreased vit B12 absorption, loss of glycemic control. Pregnancy. Elderly. Childn <18 yr. Lactation: not known if crosses into breast milk, use caution Pregnancy Categories

Indication

Type 2 DM

Contra Indication

Renal dysfunction, e.g., serum creatinine >1.5 mg/dL [males], >1.4 mg/dL [females] or abnormal creatinine clearance. Metabolic acidosis, including diabetic ketoacidosis. History of a serious hypersensitivity reaction (e.g., anaphylaxis or angioedema) to Sitagliptin + Metformin or to one of its components.

Dose

N/A

Side Effect

1-10% Abdominal pain (2.2%),Diarrhea (2.4%),Hypoglycemia (2.1%),Nausea (1.3%),Vomiting (1.1%) Frequency Not Defined Exfoliative disorder of skin of scalp,Stevens-Johnson syndrome,Lactic acidosis (rare ),Anaphylaxis/hypersensitivity reaction,Rhabdomyolysis,Acute renal failure,Angioedema

Pregnancy Category

Mode of Action

Sitagliptin: Dipeptidyl peptidase 4 (DPP-4) inhibitor, thereby increasing and prolonging incretin hormone activity which are inactivated by DPP-4 enzyme. Incretins increase insulin release and synthesis from pancreatic beta cells and reduce glucagon secretion pancreatic alpha cells. Metformin: Biguanide; acts by decreasing endogenous hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization; improves glucose tolerance and lowers both basal and postprandial plasma glucose .

Interaction

Additive effect w/ sulfonylureas. Thiazide diuretics, corticosteroids, phenothiazines, OC, sympathomimetics, niacin, Ca channel blockers and isoniazid may exacerbate loss of glycaemic control. ACE inhibitors may reduce fasting blood glucose concentrations. May increase serum level w/ cimetidine. Potentially Fatal: Concurrent use w/ iodinated contrast agents may increase the risk of metformin-induced lactic acidosis.

Pregnancy Category Note

Pregnancy There is pregnancy exposure registry that monitors pregnancy outcomes in women exposed to drug during pregnancy; health care providers are encouraged to report any prenatal exposure to drug by calling the Pregnancy Registry at 1-800-986-8999 Limited available data in pregnant women are not sufficient to inform a drug- associated risk for major birth defects and miscarriage; published studies with metformin use during pregnancy have not reported a clear association with metformin and major birth defect or miscarriage risk; there are risks to mother and fetus associated with poorly controlled diabetes in pregnancy Poorly controlled diabetes in pregnancy increases maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, still birth, and delivery complications; poorly controlled diabetes increases fetal risk for major birth defects, still birth, and macrosomia related morbidity Discuss potential for unintended pregnancy with premenopausal women as therapy with metformin may result in ovulation in some anovulatory women Lactation There is no information regarding presence in human milk, effects on breastfed infant, or on milk production; limited published studies report that metformin is present in human milk; there are no reports of adverse effects on breastfed infants exposed to metformin; there is no information on effects of metformin on milk production; sitagliptin is present in rat milk and therefore possibly present in human milk; developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and any potential adverse effects on breastfed infant from drug or from underlying maternal condition

Adult Dose

Oral Type 2 DM The recommended starting dose in patients not currently treated with Metformin Initially 50 mg/500 mg bd. The starting dose in patients already treated with Metformin should provide sitagliptin dosed as 50 mg twice daily (100 mg total daily dose) and the dose of Metformin already being taken. For patients taking Metformin 850 mg twice daily, the recommended starting dose of this combination is 50 mg Sitagliptin/1000 mg Metformin hydrochloride twice daily. May adjust the dosing based on effectiveness and tolerability. Max daily dose: Sitagliptin 100 mg/metformin 2000 mg. Extended Release Tablet: Initially: Sitagliptin 50 mg or 100 mg/metformin extended-release 500 mg or 1,000 mg. Administer once daily with meal preferably in the evening. Gradually escalate the dose twice daily if needed. Max daily dose: Sitagliptin 100 mg/metformin extended-release 2000 mg. Hepatic impairment: Do not administer

Child Dose

<18 years: Safety and efficacy not established

Renal Dose

Renal impairment Obtain eGFR before starting metformin eGFR <30 mL/min/1.73 m²: Contraindicated eGFR 30-45 mL/min/1.73 m²: Not recommended to initiate treatment Monitor eGFR at least annually or more often for those at risk for renal impairment (eg, elderly) If eGFR falls below 45mL/min/1.73 m² while taking metformin, risks and benefits of continuing therapy should be evaluated If eGFR falls below 30 mL/min/1.73 m²: while taking metformin, discontinue the drug

Administration

Should be taken with food.