XIGDUO XR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for XIGDUO XR (XIGDUO XR).
XIGDUO XR is a combination of dapagliflozin, an SGLT2 inhibitor that reduces renal glucose reabsorption, and metformin, an AMPK activator that decreases hepatic glucose production and increases insulin sensitivity.
| Metabolism | Dapagliflozin: Primarily via UGT1A9; Metformin: Not metabolized, excreted unchanged in urine. |
| Excretion | Dapagliflozin: renal (75% as unchanged drug and glucuronide metabolites); fecal (21%). Metformin: renal (90% unchanged) via tubular secretion. |
| Half-life | Dapagliflozin: terminal half-life ~12.9 hours after single dose, supporting once-daily dosing. Metformin: plasma elimination half-life ~6.2 hours; prolonged in renal impairment. |
| Protein binding | Dapagliflozin: ~91% bound to plasma proteins (albumin). Metformin: negligible binding to plasma proteins (<5%). |
| Volume of Distribution | Dapagliflozin: apparent Vd ~118 L; extensive tissue distribution. Metformin: Vd 654±358 L (mean±SD); distributes into erythrocytes and tissues. |
| Bioavailability | Dapagliflozin: absolute oral bioavailability ~78% (tablet). Metformin: absolute oral bioavailability 50-60% (immediate-release); XR formulation 100% relative to IR (bioequivalent under fed conditions). |
| Onset of Action | Dapagliflozin: onset of urinary glucose excretion within 3 hours; glycemic effects seen after 1-2 days. Metformin: onset of glucose-lowering effect within 24-48 hours; maximal effect in 1-2 weeks. |
| Duration of Action | Dapagliflozin: >24 hours due to half-life; once-daily dosing provides sustained SGLT2 inhibition. Metformin: 8-12 hours per dose; extended-release formulation allows once-daily dosing with peak at 7 hours. |
| Brand Substitutes | Switdapa M 10mg/1000mg XR Tablet, Dapazol M 10/1000 Tablet ER, Gluflozin MF Forte 10/1000 Tablet ER, Justoza M 10mg/1000mg Tablet ER, Zinodap M 10/1000 Tablet ER, Dapamac M 10mg/500mg Tablet ER, Justoza-M 10/500 Tablet ER, Sgltd M 10mg/500mg Tablet ER, Zinodap M 10mg/500mg Tablet ER, Switdapa-M 10/500 XR Tablet |
XIGDUO XR (dapagliflozin/metformin ER) usual starting dose: 5 mg dapagliflozin/500 mg metformin once daily, with gradual dose escalation based on glycemic response; maximum dose: 10 mg dapagliflozin/2000 mg metformin once daily.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | Contraindicated if eGFR <30 mL/min/1.73 m2. Not recommended if eGFR 30-45 mL/min/1.73 m2 (dapagliflozin component not effective). For eGFR 45-60 mL/min/1.73 m2, maximum dose is 5 mg dapagliflozin/1000 mg metformin. Discontinue if eGFR persistently falls below 45 mL/min/1.73 m2. |
| Liver impairment | Avoid use in Child-Pugh Class C (severe hepatic impairment). Use with caution in Child-Pugh Class B; metformin-associated lactic acidosis risk. No specific dose recommendation; assess liver function and consider alternative therapy. |
| Pediatric use | Safety and efficacy in pediatric patients (<18 years) have not been established. Not recommended. |
| Geriatric use | Start at lower dose (2.5 mg dapagliflozin/500 mg metformin if available; otherwise 5 mg/500 mg) with careful titration. Monitor renal function (eGFR) frequently due to age-related decline. Increased risk of hypovolemia, diuretic effects, and lactic acidosis. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for XIGDUO XR (XIGDUO XR).
| Breastfeeding | Not recommended during breastfeeding. Dapagliflozin: unknown if excreted in human milk; animal studies show milk excretion. Metformin: excreted in human milk (M/P ratio 0.35-0.6); infant exposure approximately 0.3% of maternal weight-adjusted dose. Theoretical risk of neonatal hypoglycemia or diarrhea. Avoid use. |
| Teratogenic Risk | XIGDUO XR (dapagliflozin/metformin extended-release) is contraindicated in the second and third trimesters due to dapagliflozin component causing increased neonatal renal morbidity and mortality. First trimester: limited data but animal studies show fetal renal toxicity at maternal exposures; caution advised. Metformin is generally low risk but associated with reduced birth weight. Overall, risk potential for urogenital and renal developmental toxicity, especially after organogenesis. |
■ FDA Black Box Warning
Lactic acidosis: Metformin-associated lactic acidosis is rare but fatal. Risk factors include renal impairment, acute heart failure, sepsis, dehydration, alcohol intake, and use of contrast agents. Discontinue if suspected.
| Serious Effects |
["Severe renal impairment (eGFR < 30 mL/min/1.73 m2)","Acute or chronic metabolic acidosis including diabetic ketoacidosis","History of serious hypersensitivity to dapagliflozin or metformin","Concomitant use of alcohol or alcohol-containing products (metformin)"]
| Precautions | ["Lactic acidosis risk","Acute kidney injury and impairment in renal function","Volume depletion, hypotension, and electrolyte imbalances","Ketoacidosis in type 2 diabetes","Urosepsis and pyelonephritis","Lower limb amputation risk (dapagliflozin)","Necrotizing fasciitis of the perineum (Fournier gangrene)","Hypoglycemia when used with insulin or insulin secretagogues","Vitamin B12 deficiency (metformin)","Genital mycotic infections","Increased LDL-C (dapagliflozin)"] |
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| Fetal Monitoring | Monitor renal function (serum creatinine, eGFR) and fetal growth via ultrasound. Assess for polyhydramnios and fetal renal abnormalities. Maternal monitoring: blood glucose, HbA1c, and blood pressure. During lactation, monitor infant for hypoglycemia and growth. |
| Fertility Effects | Metformin may improve fertility in women with PCOS by restoring ovulation. Dapagliflozin: no direct effect on fertility in animal studies, but weight loss may affect menstrual cycles. Male fertility: no significant adverse effects reported. Overall, potential indirect positive effect on fertility in insulin-resistant states. |