DAPAGLIFLOZIN AND METFORMIN
Clinical safety rating: safe
Alcohol and contrast dye can increase risk of lactic acidosis Can cause lactic acidosis a rare but serious metabolic complication.
Dapagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor that reduces renal glucose reabsorption, increasing urinary glucose excretion. Metformin is a biguanide that decreases hepatic glucose production, decreases intestinal glucose absorption, and improves insulin sensitivity.
| Metabolism | Dapagliflozin: primarily metabolized by uridine diphosphate-glucuronosyltransferase 1A9 (UGT1A9) to an inactive metabolite. Metformin: not metabolized; excreted unchanged in urine. |
| Excretion | Metformin: 90% renal unchanged; ~10% fecal. Dapagliflozin: 75% renal (mostly unchanged glucuronide), 21% fecal. |
| Half-life | Metformin: ~6.2 h (plasma), prolonged in renal impairment. Dapagliflozin: ~12.9 h (terminal), supports once-daily dosing. |
| Protein binding | Metformin: <5% bound to plasma proteins. Dapagliflozin: ~91% bound primarily to albumin. |
| Volume of Distribution | Metformin: 3.1 L/kg (extensive tissue distribution). Dapagliflozin: 1.3 L/kg (moderate distribution). |
| Bioavailability | Metformin: 40-60% (oral). Dapagliflozin: ~78% (oral). |
| Onset of Action | Metformin: 1-2 h (serum glucose reduction), peak effect 4-8 h. Dapagliflozin: Onset of urinary glucose excretion within 1 h post-dose. |
| Duration of Action | Metformin: 8-12 h (glucose lowering). Dapagliflozin: 24 h (sustained UGE), once-daily dosing. |
Initial: dapagliflozin 5 mg/metformin 500 mg orally twice daily, or dapagliflozin 5 mg/metformin 1000 mg orally twice daily. Titrate based on efficacy and tolerability. Maximum: dapagliflozin 10 mg/metformin 2000 mg per day.
| Dosage form | TABLET |
| Renal impairment | eGFR ≥60 mL/min/1.73m2: no adjustment. eGFR 45-59: maximum dapagliflozin 10 mg/metformin 1000 mg per day; limit metformin dose. eGFR 30-44: initiate dapagliflozin 5 mg once daily; maximum dapagliflozin 10 mg once daily; metformin contraindicated. eGFR <30: contraindicated. |
| Liver impairment | Child-Pugh Class A: no adjustment. Class B: not recommended due to lack of data. Class C: contraindicated (metformin associated with lactic acidosis risk). |
| Pediatric use | Not approved for pediatric patients; safety and efficacy not established in patients <18 years. |
| Geriatric use | Age ≥65 years: initiate dapagliflozin 5 mg once daily; monitor renal function and volume status. Age ≥85 years: not recommended due to reduced renal reserve. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Alcohol and contrast dye can increase risk of lactic acidosis Can cause lactic acidosis a rare but serious metabolic complication.
| FDA category | Human |
| Breastfeeding | Dapagliflozin: No human data; animal studies show excretion into milk; risk to infant unknown. Metformin: Excreted into milk with M/P ratio approximately 0.35; infant exposure 0.3-0.5% of weight-adjusted maternal dose; considered compatible with breastfeeding by most guidelines. Combination: Caution advised; monitor infant for hypoglycemia and renal effects. |
| Teratogenic Risk |
■ FDA Black Box Warning
Lactic acidosis associated with metformin accumulation; risk factors include renal impairment, concomitant use of certain drugs, age >65 years, radiologic studies with contrast, surgery, alcohol intake, hepatic impairment, and hypoxic states.
| Common Effects | Diarrhea |
| Serious Effects |
Severe renal impairment (eGFR <45 mL/min/1.73 m²), end stage renal disease, dialysis, acute or chronic metabolic acidosis including diabetic ketoacidosis, history of serious hypersensitivity to dapagliflozin or metformin.
| Precautions | Lactic acidosis risk, acute kidney injury, hypotension, ketoacidosis in type 2 diabetes, lower limb amputation, genital mycotic infections, urinary tract infections, increased LDL-C, pancreatitis, vitamin B12 deficiency (metformin), and hypersensitivity reactions. |
Loading safety data…
| First trimester: Limited human data; animal studies show renal toxicity. Second and third trimesters: Dapagliflozin may cause fetal renal dysfunction and oligohydramnios; metformin is associated with reduced risk of congenital anomalies vs insulin but may increase risk of preeclampsia. Overall, dapagliflozin is contraindicated in pregnancy due to SGLT2 inhibitor class effects. |
| Fetal Monitoring | Monitor maternal blood glucose, HbA1c, renal function (serum creatinine, eGFR), and hydration status. Fetal monitoring includes ultrasound for amniotic fluid volume and fetal growth in third trimester; assess for signs of oligohydramnios or fetal renal abnormalities. |
| Fertility Effects | Metformin may improve ovulation in women with polycystic ovary syndrome. Dapagliflozin: No significant effects on fertility in animal studies; human data limited. Combination: Possible favorable effect on metabolic parameters that may improve fertility in insulin-resistant states. |