SEGLUROMET
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SEGLUROMET (SEGLUROMET).
SEGLUROMET is a fixed-dose combination of ertugliflozin and metformin. Ertugliflozin is a sodium-glucose co-transporter 2 (SGLT2) inhibitor that reduces renal glucose reabsorption, increasing urinary glucose excretion. Metformin decreases hepatic glucose production, decreases intestinal glucose absorption, and improves insulin sensitivity.
| Metabolism | Ertugliflozin is primarily metabolized by UGT1A9 and UGT2B7 to glucuronide conjugates. Metformin is excreted unchanged in the urine, with negligible metabolism. |
| Excretion | Segluromet (ertugliflozin and metformin) is primarily excreted via renal (ertugliflozin: ~40.9% unchanged in urine; metformin: ~90% unchanged in urine) and fecal/biliary routes (ertugliflozin: ~50.2% in feces as parent and metabolites; metformin: <1% in bile). |
| Half-life | Ertugliflozin: terminal half-life ~16.6 hours (range 10-20 h), supporting once daily dosing. Metformin: terminal half-life ~6.2 hours (range 4-8.7 h) in patients with normal renal function; prolonged in renal impairment. |
| Protein binding | Ertugliflozin: ~93.6% bound to plasma proteins (mainly albumin). Metformin: negligible binding to plasma proteins (<1%). |
| Volume of Distribution | Ertugliflozin: Vd ~85.6 L (1.14 L/kg for 75 kg), indicating extensive tissue distribution. Metformin: Vd ~654 L (9.3 L/kg), suggesting high tissue uptake (predominantly in erythrocytes, GI tract, and liver). |
| Bioavailability | Ertugliflozin: absolute oral bioavailability ~98-100%. Metformin: absolute oral bioavailability ~50-60% (decreased by food; taken with meals to reduce GI side effects). |
| Onset of Action | Ertugliflozin: onset of SGLT2 inhibition within 1-2 hours post-dose; clinical glycemic effect observable after first dose. Metformin: onset of glucose-lowering effect within 1-3 days; maximal effect may take 1-2 weeks. |
| Duration of Action | Ertugliflozin: duration of action ~24 hours (once daily dosing). Metformin: duration of action ~12-24 hours, typically given twice daily with meals. |
Initial: 2.5 mg ertugliflozin/1000 mg metformin twice daily. Titrate based on efficacy and tolerability. Maximum: 5 mg ertugliflozin/2000 mg metformin twice daily.
| Dosage form | TABLET |
| Renal impairment | eGFR ≥60 mL/min/1.73 m²: No adjustment. eGFR 45-59 mL/min/1.73 m²: Maximum 5 mg ertugliflozin/1000 mg metformin twice daily. eGFR <45 mL/min/1.73 m²: Contraindicated. |
| Liver impairment | Child-Pugh Class A: No adjustment. Child-Pugh Class B or C: Contraindicated. |
| Pediatric use | Not indicated in pediatric patients. |
| Geriatric use | Initiate at lower dose; assess renal function. Avoid use if eGFR <45 mL/min/1.73 m². |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SEGLUROMET (SEGLUROMET).
| Breastfeeding | Metformin is excreted into milk; M/P ratio unknown, but levels are low. Ertugliflozin is present in animal milk; human data absent. Use with caution, as renal effects in infant are unknown. |
| Teratogenic Risk | SEGLUROMET (metformin and ertugliflozin) has limited data. Metformin is generally considered low risk in pregnancy, with some studies suggesting no increased risk of major malformations. Ertugliflozin is not recommended in second and third trimesters due to potential fetal renal toxicity. Avoid in pregnancy unless benefit outweighs risk. |
■ FDA Black Box Warning
Lactic acidosis: Metformin-associated lactic acidosis (MALA) is a rare but serious complication. Risk factors include renal impairment, acute conditions that affect renal function, concomitant use of certain drugs, age ≥65 years, radiographic studies with intravascular iodinated contrast, surgery, or other procedures, hypoxic states, excessive alcohol intake, and hepatic impairment.
| Serious Effects |
["Severe renal impairment (eGFR <30 mL/min/1.73 m²)","End-stage renal disease or dialysis","Acute or chronic metabolic acidosis, including diabetic ketoacidosis","Hypersensitivity to ertugliflozin, metformin, or any component"]
| Precautions | ["Lactic acidosis: Discontinue in clinical situations predisposing to hypoxia or renal impairment.","Volume depletion: Risk of hypotension, especially in patients with impaired renal function (eGFR <60 mL/min/1.73 m²), elderly, or on diuretics.","Ketoacidosis: Rare but serious, atypical presentation (euglycemic DKA). Discontinue if suspected.","Acute kidney injury: Monitor renal function.","Urosepsis and pyelonephritis: Evaluate for UTI.","Lower limb amputation: Increased risk, primarily toe amputations; monitor for signs or symptoms.","Genital mycotic infections: Increased risk.","Hypoglycemia: When used with insulin or sulfonylureas.","Vitamin B12 deficiency: Long-term metformin use; monitor levels.","Increased LDL-C: Monitor lipid profile.","Severe and disabling arthralgia: Consider discontinuation."] |
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| Fetal Monitoring |
| Monitor maternal renal function (serum creatinine, eGFR) and blood glucose. Assess fetal growth and amniotic fluid volume, especially with use in second/third trimester. Monitor for signs of volume depletion in mother. |
| Fertility Effects | No specific data on SEGLUROMET. Metformin may improve ovulation in women with PCOS. Ertugliflozin may affect hormonal balance via weight loss; impact on fertility is not established. |