Indicated as adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus who are already treated with sitagliptin or metformin and have inadequate glycemic control on sitagliptin or metformin alone Adjust dose gradually considering effectiveness and tolerability 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 Gastrointestinal: Constipation, vomiting Neurologic: Headache Worsening renal function, including acute renal failure (sometimes requiring dialysis) Myalgia, pain in extremity, and back pain Severe disabling arthralgia Pruritus Mouth ulceration; stomatitis Discontinue metformin at the time of or before an iodinated contrast imaging procedure in patients with an e GFR between 30-60 m L/minute/1.73 m²; in patients with a history of liver disease, alcoholism, or heart failure; or in patients who will be administered intra-arterial iodinate contrast 80 years only if Cr Cl 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 materials and for any surgical procedure Risk of hypoglycemia esp 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 Unknown if patients with history of pancreatitis are at increased risk 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 a possible cause for severe joint pain and discontinue drug if appropriate Cases of lactic acidosis reported primarily in diabetic patients with significant renal impairment, including both intrinsic renal disease and renal hypoperfusion, often in the setting of multiple concomitant medical/surgical problems and multiple concomitant medications; monitor renal function of the elderly closely; withhold metformin promptly in presence of any condition associated with hypoxemia, dehydration, or sepsis The postmarketing metformin-associated lactic acidosis cases primarily occurred in patients with significant renal impairment; the risk of metformin accumulation and metformin-associated lactic acidosis increases with severity of renal impairment because metformin is substantially excreted by the kidney 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 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 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 Gradually escalate the dose to reduce the gastrointestinal side effects due to metformin Immediate-release: Administer q12hr with meals Extended-release: Administer once daily, with a meal preferably in the evening Maintain the same total daily dose of sitagliptin and metformin when changing between immediate-release and extended-release, without exceeding the maximum recommended daily dose Swallow whole; do not split, crush, or chew The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information. Biguanides lower your blood-glucose level by attenuating your liver glucose production, boost glucose update by improving insulin sensitivity. You may lose some weight when you start taking metformin, which further helps your diabetes control. Metformin can additionally improve blood cholesterol levels, which are often a problem among type 2 diabetes. Metformin is primarily used in the obese not responding to dietary therapy. Metformin can increase insulin sensitivity and reduce insulin requirements. Additionally, biguanides can lower fasting levels of insulin in plasma. Metformin is suitable for a mono-therapy and in combination with sulfonylureas and other secretagogues, thiazolidinediones, and insulin. 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