Drug reference

Metformin + Dapagliflozin

SGLT2 Inhibitor · Antidiabetic

Also known as Xigduo XR, Forxiga-M, Oxra-M, SGLT2-M

SGLT2 InhibitorAntidiabeticATC A10BD21

CDSCO approvedSchedule HATC A10BD21

Pharmacokineticsplasma · t hours

ONSET: 45min · Dapagliflozin: within 30-60 minutes. Metformin: within hours.
PEAK: 2.5h · Dapagliflozin: approximately 2 hours. Metformin: 2-3 hours (immediate release), 4-8 hours (extended release).
t½: 12.9h · Dapagliflozin: approximately 12.9 hours. Metformin: approximately 6.2 hours (plasma), 17.6 hours (blood).
DURATION: 1d · Both components provide effects for approximately 24 hours.

EXCRETION

—

not curated

INTERACTIONS

—

none in our sources

PREGNANCY

Not recommended during pregnancy. Metformin is classified as Category B; Dapagliflozin is classified as Category C (earlier classifications). Animal studies show potential for adverse renal effects in late gestation with dapagliflozin.

FDA category + note

Mechanism

Metformin, a biguanide, reduces hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. Dapagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, reduces renal glucose reabsorption, leading to increased urinary glucose excretion independent of insulin. Together, they provide complementary actions to improve glycemic control in Type 2 Diabetes Mellitus. Combination rationale: The combination of metformin and dapagliflozin provides synergistic glycemic control through distinct, complementary mechanisms of action. Metformin addresses insulin resistance and hepatic glucose output, while dapagliflozin enhances urinary glucose excretion. This combination not only improves HbA1c effectively but also offers significant cardiovascular and renal protective benefits, while reducing the pill burden for patients with Type 2 Diabetes Mellitus.

Indications

As an adjunct to diet and exercise to improve glycemic control in adults with Type 2 Diabetes MellitusTo reduce the risk of cardiovascular death and hospitalization for heart failure in adults with Type 2 Diabetes Mellitus and established cardiovascular disease or multiple cardiovascular risk factorsTo reduce the risk of sustained eGFR decline, end-stage kidney disease, cardiovascular death, and hospitalization for heart failure in adults with chronic kidney disease (CKD) at risk of progression

Dosing

Adult: Initial dose is typically Dapagliflozin 5mg/Metformin 500mg or 1000mg orally once daily, usually with the evening meal. Dose can be titrated based on efficacy and tolerability. Common strengths available in India include Dapagliflozin 5mg/Metformin 500mg, 5mg/1000mg, 10mg/500mg, and 10mg/1000mg.
Pediatric: Safety and efficacy have not been established in pediatric patients under 18 years of age.
Renal adjustment: Contraindicated if eGFR <30 mL/min/1.73 m². If eGFR is 30-44 mL/min/1.73 m², initiate dapagliflozin 5mg once daily; metformin dose might need adjustment or cessation. If eGFR is 45-59 mL/min/1.73 m², initiate dapagliflozin 10mg once daily; metformin might need dose reduction.
Hepatic adjustment: Dapagliflozin does not require dose adjustment for mild to moderate hepatic impairment; use with caution in severe hepatic impairment. Metformin is generally not recommended in patients with severe hepatic impairment.
Geriatric: No dose adjustment based on age alone is required. However, assess renal function more frequently in elderly patients. Initiate with lower doses and titrate carefully.
Max dose: Maximum daily dose of dapagliflozin is 10 mg. Maximum daily dose of metformin is 2000 mg.

Pharmacokinetics

Onset

Dapagliflozin: within 30-60 minutes. Metformin: within hours.

Peak effect

Dapagliflozin: approximately 2 hours. Metformin: 2-3 hours (immediate release), 4-8 hours (extended release).

Duration

Both components provide effects for approximately 24 hours.

Half-life

Dapagliflozin: approximately 12.9 hours. Metformin: approximately 6.2 hours (plasma), 17.6 hours (blood).

Bioavailability

Dapagliflozin: approximately 78%. Metformin: 50-60% (absolute, after a 500 mg oral dose).

Protein binding

Dapagliflozin: approximately 91%. Metformin: negligible.

Metabolism

Dapagliflozin: extensively metabolized via O-deglucuronidation by UGT1A9 to inactive metabolites. Metformin: not metabolized in humans.

Excretion

Dapagliflozin: primarily renal (75% as metabolites). Metformin: primarily renal (unchanged).

Contraindications

Severe renal impairment (eGFR <30 mL/min/1.73 m²)
Metabolic acidosis, including diabetic ketoacidosis (DKA)
Hypersensitivity to metformin hydrochloride or dapagliflozin
Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma
History of serious hypersensitivity reaction to dapagliflozin

Side effects

Common

Genital mycotic infections (vulvovaginal candidiasis, balanitis)Urinary tract infectionsDiarrheaNauseaFlatulenceAbdominal discomfortIncreased urination (polyuria/pollakiuria)ThirstHeadacheDyslipidemia

Serious

Lactic acidosis (rare, but serious with metformin, especially in renal impairment)
Diabetic ketoacidosis (DKA), even with normal or mildly elevated blood glucose levels
Fournier's gangrene (perineal necrotizing fasciitis)
Hypoglycemia (especially with concomitant use of insulin or sulfonylureas)
Dehydration and hypotension
Acute kidney injury
Hypersensitivity reactions
Vitamin B12 deficiency (with long-term metformin use)

Pregnancy & lactation

Pregnancy

Lactation

It is unknown whether dapagliflozin or metformin are excreted in human milk. Due to the potential for serious adverse reactions in a breastfed infant, breastfeeding is not recommended during treatment with this combination.