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. |
| Molecular Weight | Metformin hydrochloride: 165.62 Da (as HCl salt; base: 129.16 Da); ertugliflozin: 436.94 Da |
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 | Avoid unless benefit outweighs risk; not recommended due to insufficient human data and potential for fetal harm based on animal studies showing decreased fetal weight and increased skeletal variations at maternal toxic doses. |
| 2nd trimester | Avoid unless benefit outweighs risk; not recommended due to insufficient human data and potential for fetal harm. Consider other glucose-lowering agents with established safety profiles. |
| 3rd trimester | Avoid unless benefit outweighs risk; not recommended. May increase risk of neonatal hypoglycemia and other adverse outcomes. Insulin is preferred for glycemic control during pregnancy. |
Clinical note
Comprehensive clinical and safety monograph for SEGLUROMET (SEGLUROMET).
| Placental transfer | Predicted to cross the placenta based on molecular weight (metformin component: ~129 Da; ertugliflozin component: ~436 Da) and animal studies showing transfer of ertugliflozin across the placenta in rats. Human data are lacking. |
| Breastfeeding |
■ 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 dialysisAcute or chronic metabolic acidosis, including diabetic ketoacidosisHypersensitivity to metformin, ertugliflozin, or any components of the productBreastfeeding (due to potential risk)Pregnancy (contraindicated per labeling; use not recommended)
| 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. |
Loading safety data…
| Excretion into human milk is unknown. Due to potential for serious adverse reactions in nursing infants, including hypoglycemia, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. |
| Lactation Rating | L4 - Possibly Hazardous (FDA: Not recommended; similar to metformin, which is excreted into milk; limited data on ertugliflozin transfer; risk of infant hypoglycemia and other adverse effects). |
| 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. |
| 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. |
| Food/Dietary | Avoid excessive alcohol intake; may increase risk of lactic acidosis and hypoglycemia. No specific food restrictions but take with meals to reduce gastrointestinal upset. |
| Clinical Pearls | SEGLUROMET combines ertugliflozin and metformin. Ertugliflozin is an SGLT2 inhibitor; monitor for genital mycotic infections, volume depletion, and rare ketoacidosis. Metformin may cause lactic acidosis; contraindicated if eGFR <30 mL/min/1.73 m². Assess renal function before initiation and periodically. Use with caution in patients on diuretics or ACE inhibitors due to hypotension risk. |
| Patient Advice | Take with meals to reduce metformin gastrointestinal side effects. · Maintain adequate fluid intake to prevent dehydration. · Monitor for signs of urinary tract or genital fungal infections and report promptly. · Seek immediate medical attention for symptoms of lactic acidosis (e.g., unusual tiredness, muscle pain, abdominal discomfort). · Do not skip or double doses; if a dose is missed, take it with the next meal unless almost time for the next dose. · Regularly check blood glucose as directed. · Carry a medical alert identification indicating diabetes. · Avoid alcohol or limit intake due to increased risk of lactic acidosis and hypoglycemia. |