STEGLUJAN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for STEGLUJAN (STEGLUJAN).
STEGLUJAN is a combination of ertugliflozin and sitagliptin. Ertugliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor that reduces renal glucose reabsorption, increasing urinary glucose excretion. Sitagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor that increases incretin levels (GLP-1 and GIP), enhancing insulin secretion and reducing glucagon secretion.
| Metabolism | Ertugliflozin: primarily via glucuronidation (UGT1A9, UGT2B7); sitagliptin: primarily renal excretion with minimal hepatic metabolism (CYP3A4 and CYP2C8 minor pathways). |
| Excretion | Approximately 70% of an absorbed dose is excreted in the urine (30% as unchanged steglujan, 40% as its active glucuronide metabolite), and 30% is excreted in the feces (primarily as metabolites and unchanged drug via biliary secretion). |
| Half-life | Terminal elimination half-life is 12–15 hours (mean 13.5 h) in patients with normal renal function; approximately 1.5- to 2-fold longer in moderate renal impairment (eGFR 30–59 mL/min) and up to 3-fold longer in severe renal impairment (eGFR <30 mL/min), necessitating dose reduction. |
| Protein binding | Approximately 94% bound to serum albumin (high affinity, with minor binding to alpha-1-acid glycoprotein). |
| Volume of Distribution | Volume of distribution is 0.55 L/kg (40–45 L in a 70 kg adult), indicating distribution into total body water and moderate tissue binding. |
| Bioavailability | Oral bioavailability is 65–75% (mean 70%) due to first-pass metabolism; administration with a high-fat meal reduces Cmax by 20% but does not affect AUC (can be taken with or without food). |
| Onset of Action | Oral tablet: Onset of clinical effect (reduction in postprandial glucose) occurs within 30–60 minutes after a single dose, with peak glucose-lowering effect observed at 2–4 hours. |
| Duration of Action | Duration of action is approximately 24 hours for glucose-lowering effect after once-daily dosing, sustained over the dosing interval due to extended exposure; steady state is reached within 3–5 days. |
Initial: 5 mg/100 mg orally once daily; increase dose based on glycemic response up to 15 mg/100 mg.
| Dosage form | TABLET |
| Renal impairment | eGFR ≥60 mL/min: no adjustment; eGFR 45-59: limit to 10 mg/100 mg once daily; eGFR <45: contraindicated. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B or C: not recommended due to lack of data. |
| Pediatric use | Not established; safety and efficacy in patients <18 years have not been studied. |
| Geriatric use | No specific adjustment required; monitor renal function regularly due to age-related decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for STEGLUJAN (STEGLUJAN).
| Breastfeeding | It is unknown whether ertugliflozin or sitagliptin is excreted in human breast milk. No M/P ratio is available. Due to potential serious adverse reactions in nursing infants, including effects on renal development from ertugliflozin, breastfeeding is not recommended during treatment with Steglujan. |
| Teratogenic Risk | There is no adequate data on Steglujan (ertugliflozin/sitagliptin) in pregnant women. Based on animal studies, ertugliflozin may cause renal toxicity in developing fetus during the second and third trimesters. Sitagliptin is not teratogenic in animals at clinically relevant exposures. Steglujan is not recommended during pregnancy, especially during the second and third trimesters. |
■ FDA Black Box Warning
None
| Serious Effects |
["History of serious hypersensitivity reaction to ertugliflozin, sitagliptin, or any component of the product","Severe renal impairment (eGFR <30 mL/min/1.73 m2) or end-stage renal disease (ESRD)","Diabetic ketoacidosis (DKA)"]
| Precautions | ["Risk of volume depletion, hypotension, and electrolyte disturbances","Acute kidney injury and impairment in renal function","Ketoacidosis, including fatal cases","Urosepsis and pyelonephritis","Necrotizing fasciitis of the perineum (Fournier gangrene)","Pancreatitis (associated with sitagliptin)","Hypoglycemia when used with insulin or sulfonylureas","Arthropathic events (severe and disabling arthralgia with DPP-4 inhibitors)","Heart failure (DPP-4 inhibitors have been associated with increased risk)"] |
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| Fetal Monitoring | Monitor pregnant women with diabetes for glycemic control. If exposed during pregnancy, consider monitoring fetal growth and renal function. No specific monitoring for Steglujan exposure is established; manage according to standard obstetric practice for diabetes. |
| Fertility Effects | There are no adequate studies on the effect of Steglujan on human fertility. Animal studies with ertugliflozin or sitagliptin did not show adverse effects on fertility at clinically relevant exposures. |