Empagliflozin + Metformin

Oral
Type 2 diabetes mellitus

ESRD and patients undergoing dialysis: Contraindicated. eGFR <30 mL/min/1.73 m²: Contraindicated. eGFR <45 mL/min/1.73 m²: Not recommended. Dosage and treatment recommendations may vary among countries and between individual products (refer to specific product guidelines).

Contraindicated.

Empagliflozin + Metformin Should be taken with food.

Diabetic pre-coma; acute or chronic metabolic acidosis (e.g. diabetic ketoacidosis with or without coma, lactic acidosis), alcoholism or acute alcohol intoxication; acute or chronic disease that may cause hypoxia (e.g. cardiac or respiratory failure, recent MI); acute conditions that may alter renal function (e.g. severe infection, dehydration, shock). Hepatic and severe renal impairment (eGFR <30 mL/min/1.73 m²) including ESRD and patients on dialysis. Concomitant intravascular administration of iodinated contrast agents.

Patient with hypotension; risk factors for acute kidney injury (e.g. hypovolaemia); predisposition to diabetic ketoacidosis including patients on a very low carbohydrate diet, pancreatic disorders suggesting insulin deficiency (e.g. history of pancreatitis or pancreatic surgery), insulin dose reduction, caloric restriction, alcohol abuse, acute febrile illness, severe dehydration; history of genital mycotic infections; stress-related states (e.g. infection, fever, trauma, surgery). Patients undergoing surgery. Consider temporary treatment discontinuation for at least 3 days prior to surgery. Hospitalised patients. Not indicated for use in patients with type 1 diabetes mellitus. Mild to moderate renal impairment (eGFR <45 mL/min/1.73 m²). Elderly. Pregnancy and lactation.

Significant: Bone fractures, genital mycotic infections (e.g. vulvovaginal mycotic infection, vulvovaginal candidiasis, vulvovaginitis, candida balanitis, balanoposthitis), hypersensitivity reactions (e.g. angioedema, rash, urticaria), symptomatic hypotension, acute kidney injury, severe UTI (including urosepsis and pyelonephritis); hepatic injury; vitamin B₁₂ deficiency (prolonged use); hypoglycaemia (particularly when used concomitantly with insulin or insulin secretagogues).
Gastrointestinal disorders: Nausea, vomiting, diarrhoea, abdominal pain, constipation, taste disturbance.
Investigations: Increased haematocrit.
Metabolism and nutrition disorders: Loss of appetite, thirst.
Renal and urinary disorders: Increased urination.
Potentially Fatal: Lactic acidosis, diabetic ketoacidosis. Rarely, necrotising fasciitis of the perineum (Fournier's gangrene).

Monitor serum glucose, HbA_1c (twice a year for those who have stable glycaemic control and are meeting the treatment goals; quarterly for patients not meeting the treatment goals or with therapy changes), renal function (before treatment initiation and as clinically indicated), volume status (e.g. blood pressure, electrolytes), haematologic parameters (e.g. Hb, haematocrit, RBC indices) annually, vitamin B₁₂ serum concentration every 1-2 years (particularly to those with risk factors for vitamin B deficiency). Assess for signs and symptoms of genital mycotic infection, UTI, heart failure, diabetic foot infection, lactic acidosis and ketoacidosis.

Symptoms: Metformin: Lactic acidosis. Management: Prompt supportive treatment instituted in the hospital setting. May perform haemodialysis to remove metformin and lactate.

Empagliflozin: Increased risk of hypoglycaemia with insulin and insulin secretagogues (e.g. sulfonylureas). May potentiate diuretic effect and increase risk of hypotension and dehydration with thiazides and loop diuretics. May enhance the renal excretion of lithium and reduce the blood lithium levels.
Metformin: May increase risk of lactic acidosis with topiramate or other carbonic anhydrase inhibitors (e.g. zonisamide, acetazolamide, dichlorphenamide), NSAIDs (including COX-2 inhibitors, ACE inhibitors, angiotensin II receptor antagonists, diuretics [especially loop diuretics]). Enhanced gastrointestinal absorption and efficacy with organic cation transporters-1 (OCT1) inducers (e.g. rifampicin). Reduced efficacy with OCT1 inhibitors (e.g. verapamil). Decreased renal elimination resulting in increased plasma concentration with organic cation transporters (OCT2) inhibitors (e.g. cimetidine, dolutegravir, isavuconazole, ranolazine, trimethoprim, vandetanib). Altered efficacy and renal elimination with OCT1 and OCT2 inhibitors (e.g. crizotinib, olaparib).
Potentially Fatal: Metformin: May cause contrast-induced nephropathy leading to metformin accumulation and increased risk of lactic acidosis with intravascular iodinated contrast agents.

Metformin: Food decreases and slightly delays absorption. Alcohol may potentiate the risk of lactic acidosis.

Empagliflozin: May cause false-positive result for urine glucose test. May interfere with 1,5-anhydrogluicitol (1,5-AG) assay.

Description:
Mechanism of Action: Empagliflozin is a potent, selective, and reversible inhibitor of sodium-glucose co-transporter 2 (SGLT2), the main transporter responsible for glucose reabsorption from the glomerular filtrate back into the circulation. Inhibition of SGLT2 causes a reduction in the reabsorption of filtered glucose and lowers renal threshold for glucose, thereby increasing urinary glucose excretion and reducing serum glucose concentration. Additionally, empagliflozin increases Na delivery to the distal tubule and decreases Na reabsorption, which may lead to reduced cardiac preload and afterload and downregulation of sympathetic activity.
Metformin is a biguanide antidiabetic agent that improves glucose tolerance by lowering both basal and postprandial plasma glucose. It reduces hepatic glucose production by inhibiting gluconeogenesis and glycogenolysis, delays intestinal absorption of glucose, and enhances insulin sensitivity by improving peripheral glucose uptake and utilisation in the muscle.
Pharmacokinetics:
Absorption: Empagliflozin: Rapidly absorbed from the gastrointestinal tract. Time to peak plasma concentration: Approx 1.5 hours.
Metformin: Slowly and incompletely absorbed from the gastrointestinal tract. Food decreases and slightly delays absorption. Absolute bioavailability: Approx 50-60%. Time to peak plasma concentration: 2-3 hours.
Distribution: Empagliflozin: Plasma protein binding: 86.2%.
Metformin: Partitions into erythrocytes; concentrates in kidney, liver, and gastrointestinal tract. Crosses the placenta; enters breast milk (small amounts). Volume of distribution: 654 ± 358 L.
Metabolism: Empagliflozin: Metabolised mainly via glucuronidation by uridine diphosphate glucuronosyltransferases UGT2B7, UGT1A3, UGT1A8, and UGT1A9 into minor metabolites.
Excretion: Empagliflozin: Via urine (54.4%; 50% as unchanged drug); faeces (41.2%, mainly as unchanged drug). Terminal elimination half-life: Approx 12.4 hours.
Metformin: Via urine (90% as unchanged drug). Elimination half-life: 4-9 hours (plasma); approx 17.6 hours (blood).

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 11949646, Empagliflozin. https://pubchem.ncbi.nlm.nih.gov/compound/Empagliflozin. Accessed Nov. 25, 2024.

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 4091, Metformin. https://pubchem.ncbi.nlm.nih.gov/compound/Metformin. Accessed Apr. 29, 2025.

Store between 15-30°C.

Antidiabetic Agents

A10BD20 - metformin and empagliflozin ; Belongs to the class of combinations of oral blood glucose lowering drugs. Used in the treatment of diabetes.

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