Ertugliflozin (Monograph)

Brand name: Steglatro
Drug class: Sodium-glucose Cotransporter 2 (SGLT2) Inhibitors

Medically reviewed by Drugs.com on Apr 10, 2025. Written by ASHP.

Introduction

Antidiabetic agent; sodium-glucose cotransporter 2 (SGLT2) inhibitor.

Uses for Ertugliflozin

Type 2 Diabetes Mellitus

Glycemic Control

Used as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Used as monotherapy or in combination with other antidiabetic agents (e.g., metformin, sitagliptin, sulfonylurea, insulin).

Commercially available as a single entity preparation and in fixed combination with metformin (Segluromet) or sitagliptin (Steglujan).

Guidelines from the American Diabetes Association (ADA) and other experts generally recommend the use of SGLT2 inhibitors and/or glucagon-like peptide 1 receptor agonists in patients with type 2 diabetes and established/high risk of atherosclerotic cardiovascular disease (ASCVD), heart failure, and/or chronic kidney disease. When selecting treatment regimen, consider factors such as cardiovascular and renal comorbidities, drug efficacy and adverse effects, hypoglycemic risk, presence of overweight or obesity, cost, access, and patient preferences. Weight management should be included as a distinct treatment goal and other healthy lifestyle behaviors should also be considered.

Not indicated for treatment of type 1 diabetes mellitus.

Not indicated to improve glycemic control in type 2 diabetes mellitus in patients with eGFR <45 mL/minute per 1.73 m².

Reduction in Risk of Cardiovascular Events

Some SGLT2 inhibitors (e.g., canagliflozin, dapagliflozin, empagliflozin) have demonstrated cardiovascular risk reduction benefits^{† [off-label]} in patients with type 2 diabetes mellitus and established ASCVD (or high risk of ASCVD). In addition to lowering blood glucose, SGLT2 inhibitors appear to modify nonglycemic cardiovascular risk factors such as blood pressure, body weight, adiposity, and arterial stiffness.

In a cardiovascular outcomes trial, ertugliflozin did not demonstrate a statistically significant reduction in major adverse cardiovascular events, but secondary outcome of heart failure hospitalizations appeared to be consistent with the effects observed in other SGLT2 inhibitor trials.

For the treatment of patients with type 2 diabetes mellitus and established ASCVD (or high risk of ASCVD), current clinical practice guidelines generally recommend use of an SGLT2 inhibitor with proven efficacy in cardiovascular outcome trials.

Beneficial Effects on Renal Function

Some SGLT2 inhibitors (e.g., canagliflozin, dapagliflozin, empagliflozin) have demonstrated beneficial effects on renal function^{† [off-label]} in patients with type 2 diabetes mellitus and chronic kidney disease (CKD).

Efficacy of ertugliflozin was not demonstrated in a study in patients with type 2 diabetes mellitus and stage 3 CKD (estimated GFR ≥30 to <60 mL/min/1.73 m²).

For the treatment of patients with type 2 diabetes mellitus and CKD, current clinical practice guidelines generally recommend use of an SGLT2 inhibitor with proven benefit in reducing adverse renal outcomes.

Ertugliflozin Dosage and Administration

General

Pretreatment Screening

• Assess renal function.

• Assess volume status; volume depletion should be corrected prior to initiation.

Patient Monitoring

• Assess renal function as clinically indicated.

• Monitor for signs and symptoms of volume depletion.

• Monitor for signs and symptoms of urinary tract and genital mycotic infections.

• Monitor for infections or ulcers of the lower limbs.

Dispensing and Administration Precautions

• The Institute for Safe Medication Practices (ISMP) includes Steglatro (ertugliflozin) and Spravato (esketamine) on the ISMP List of Confused Drug Names, and recommends special safeguards to ensure the accuracy of prescriptions for these drugs.

Other General Considerations

• Withhold ertugliflozin therapy for at least 4 days, if possible, prior to major surgery or procedures requiring prolonged fasting. Resume therapy when patient is stable and has resumed oral intake.

Administration

Oral Administration

Commercially available as single-entity tablets or in fixed combination with sitagliptin (Steglujan) or immediate-release metformin hydrochloride (Segluromet).

Ertugliflozin: Administer once daily in the morning with or without food.

Fixed combination of ertugliflozin and metformin hydrochloride: Administer twice daily with meals.

Fixed combination of ertugliflozin and sitagliptin: Administer once daily in the morning with or without food.

If a dose of ertugliflozin is missed, it should be taken as soon as it is remembered followed by resumption of regular schedule. If missed dose is not remembered until it is almost time for next dose, missed dose should be skipped and regular schedule resumed. Dose should not be doubled to make up for missed dose.

Dosage

Available as ertugliflozin L-pyroglutamic acid; dosage expressed in terms of ertugliflozin.

Adults

Type 2 Diabetes Mellitus

Ertugliflozin

Oral

Initially, 5 mg once daily.

If well tolerated, increase dosage to 15 mg once daily in patients who require additional glycemic control.

Ertugliflozin/Metformin Hydrochloride Fixed-combination Therapy

Oral

Initial dosage based on patient's current regimen with ertugliflozin and/or metformin hydrochloride. May increase dosage gradually based on effectiveness and tolerability to maximum of 15 mg of ertugliflozin and 2 g of metformin hydrochloride daily.

Patients currently receiving metformin hydrochloride: Initially, total daily dosage of 5 mg of ertugliflozin (administered as fixed-combination tablets containing 2.5 mg of ertugliflozin) and a metformin hydrochloride dosage similar to patient's existing total daily dosage, given in 2 divided doses daily.

Patients currently receiving ertugliflozin: Initially, total daily dosage of 1 g of metformin hydrochloride (administered as fixed-combination tablets containing 500 mg of metformin hydrochloride) and an ertugliflozin dosage similar to the patient's existing total daily dosage, given in 2 divided doses daily.

Patients currently receiving ertugliflozin and metformin hydrochloride (administered as separate tablets): Initially, give fixed combination containing same total daily dosage of ertugliflozin and a metformin hydrochloride dosage similar to patient's existing total daily dosage, in 2 divided doses daily.

Ertugliflozin/Sitagliptin Fixed-combination Therapy

Oral

Initially, 5 mg of ertugliflozin and 100 mg of sitagliptin once daily in the morning without regard to meals.

If well tolerated, increase dosage to 15 mg of ertugliflozin and 100 mg of sitagliptin once daily in patients who require additional glycemic control.

Patients currently receiving ertugliflozin: Maintain current ertugliflozin dosage with sitagliptin 100 mg once daily.

Special Populations

Hepatic Impairment

Ertugliflozin Monotherapy

Oral

Mild or moderate hepatic impairment: No dosage adjustment necessary.

Severe hepatic impairment: Data lacking; use not recommended.

Ertugliflozin/Metformin Hydrochloride Fixed-combination Therapy

Oral

Use of fixed combination of ertugliflozin and metformin hydrochloride not recommended.

Ertugliflozin/Sitagliptin Fixed-combination Therapy

Oral

Mild or moderate hepatic impairment: No dosage adjustment necessary.

Severe hepatic impairment: Data lacking; use not recommended.

Renal Impairment

Ertugliflozin Monotherapy

Oral

Use not recommended when eGFR <45 mL/minute per 1.73 m².

Ertugliflozin/Metformin Hydrochloride Fixed-combination Therapy

Oral

Use not recommended when eGFR <45 mL/minute per 1.73 m².

Severe renal impairment (eGFR <30 mL/minute per 1.73 m²), end stage kidney disease, dialysis: Contraindicated.

Ertugliflozin/Sitagliptin Fixed-combination Therapy

Oral

Use not recommended when eGFR <45 mL/minute per 1.73 m².

Severe renal impairment (eGFR <30 mL/minute per 1.73 m²), end stage kidney disease, dialysis: Contraindicated.

Geriatric Patients

No dosage adjustment necessary based solely on age. Renal function should be monitored more frequently after initiation.

Cautions for Ertugliflozin

Contraindications

• Hypersensitivity to ertugliflozin or any ingredient in the formulation.

Warnings/Precautions

Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis

Ketoacidosis requiring hospitalization reported in patients with type 1 or type 2 diabetes mellitus receiving SGLT2 inhibitors; may occur without markedly elevated blood glucose concentrations (e.g., <250 mg/dL).

Evaluate for presence of ketoacidosis in patients experiencing severe metabolic acidosis regardless of the patient's blood glucose concentration; discontinue ertugliflozin and initiate appropriate treatment if confirmed. Monitor patient for resolution prior to restarting the drug.

Prior to initiating ertugliflozin therapy, consider factors that may predispose patients to ketoacidosis (e.g., insulin deficiency, reduced caloric intake, acute febrile illness, ketogenic diet, surgery, volume depletion, alcohol abuse). Risk factors for development of ketoacidosis should be resolved prior to initiation.

Educate patients on signs and symptoms of ketoacidosis and instruct them to discontinue ertugliflozin and seek medical attention immediately if signs and symptoms occur.

Withhold ertugliflozin if possible in temporary clinical situations that may predispose patients to ketoacidosis; resume therapy once patient is clinically stable and able to resume oral intake. For patients who undergo scheduled surgery or procedures associated with prolonged fasting, withhold ertugliflozin for ≥4 days if possible.

Some clinicians suggest monitoring of urine and/or plasma ketone levels if patients feel unwell, regardless of ambient glucose concentrations.

Lower Limb Amputation

Lower limb amputations reported with therapy. In a long-term cardiovascular outcomes study, occurrence of non-traumatic lower limb amputations was reported with event rates of 4.7, 5.7, and 6.0 events per 1000 patient-years in placebo, ertugliflozin 5 mg, and ertugliflozin 15 mg treatment arms, respectively. Amputations of toe and foot were most frequent; some patients had multiple amputations, some involving both lower limbs.

Lower limb infections, gangrene, and diabetic foot ulcers were most common precipitating medical events leading to need for amputation. Patients with amputations were more likely to be male, having higher hemoglobin A_1c at baseline, have a history of peripheral artery disease, amputation, or peripheral revascularization procedure, diabetic foot, and to have been taking diuretics or insulin.

Before initiating, consider factors in history that may predispose to need for amputations, such as history of amputation, peripheral vascular disease, neuropathy, and diabetic foot ulcers.

Counsel patients on importance of routine preventative foot care. Monitor for signs and symptoms of infection (including osteomyelitis), new pain or tenderness, and sores or ulcers involving lower limbs, and discontinue if these complications occur.

Volume Depletion

May cause intravascular volume depletion. Symptomatic hypotension or acute transient changes in serum creatinine can occur, particularly in patients with impaired renal function (eGFR <60 mL/minute per 1.73 m²), geriatric patients, or patients receiving loop diuretics.

Prior to initiation in patients with one or more of these characteristics, assess volume status and renal function. Correct intravascular volume depletion prior to initiating ertugliflozin.

Monitor patients for signs and symptoms of volume depletion and assess renal function after initiating therapy.

Urosepsis and Pyelonephritis

Treatment with an SGLT2 inhibitor increases risk for urinary tract infections. Serious urinary tract infections (e.g., urosepsis, pyelonephritis requiring hospitalization) reported in patients receiving an SGLT2 inhibitor.

Prior to initiating ertugliflozin therapy, consider patient factors that may predispose to serious urinary tract infections (e.g., history of difficulty urinating; infection of the bladder, kidneys, or urinary tract).

Monitor patients for urinary tract infections and initiate treatment if indicated.

Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogue

When adding ertugliflozin to therapy with an insulin secretagogue (e.g., sulfonylurea) or insulin, consider reducing dosage of concomitant insulin secretagogue or insulin to reduce risk of hypoglycemia.

Necrotizing Fasciitis of the Perineum (Fournier's Gangrene)

Fournier's gangrene (necrotizing fasciitis of the perineum), a rare but serious life-threatening bacterial infection requiring urgent surgical intervention, reported during postmarketing surveillance of males and females with type 2 diabetes mellitus receiving an SGLT2 inhibitor.

Assess patients for necrotizing fasciitis if pain or tenderness, erythema, or swelling in genital or perineal area occurs in addition to fever or malaise.

If Fournier's gangrene suspected, discontinue ertugliflozin and initiate treatment immediately with broad-spectrum antibiotics and, if necessary, surgical debridement. Closely monitor blood glucose concentrations and initiate alternative antidiabetic agent to maintain glycemic control.

Genital Mycotic Infections

Increases risk of genital mycotic infections in males (e.g., balanitis) and females (e.g., vulvovaginal mycotic infection). Patients with a history of genital mycotic infections and uncircumcised males are more likely to develop such infections.

Monitor patients for genital mycotic infections and institute appropriate treatment if these infections occur.

Laboratory Test Interference

SGLT2 inhibitors, including ertugliflozin, increase urinary glucose excretion and result in false-positive urine glucose tests. Manufacturer states that 1,5-anhydroglucitol assay unreliable for monitoring glycemic control in patients taking SGLT2 inhibitors. Alternate methods of monitoring glycemic control should be used.

Use of Fixed Combinations

When ertugliflozin is used in fixed combination with metformin hydrochloride, sitagliptin, or other drugs, consider the cautions, precautions, contraindications, and drug interactions associated with the concomitant agent(s) in addition to those associated with ertugliflozin.

Specific Populations

Pregnancy

Insufficient data to evaluate drug-associated risk of adverse developmental outcomes. Studies in animals indicate that ertugliflozin use during pregnancy may affect renal development and maturation, especially during the second and third trimesters of pregnancy.

Poorly controlled diabetes mellitus during pregnancy carries risks to the mother and fetus; however, ertugliflozin therapy is not recommended in pregnant women during the second and third trimesters of pregnancy.

Lactation

No data on presence of ertugliflozin in human milk, effects on breast-fed child, or effects on milk production. Distributed into milk in rats. Not recommended for use in women who are breast-feeding.

Pediatric Use

Safety and efficacy not established.

Geriatric Use

In clinical trials, geriatric patients receiving ertugliflozin more likely to experience certain adverse reactions related to volume depletion compared with younger patients.

Hepatic Impairment

Data lacking on the use of ertugliflozin in patients with severe hepatic impairment; such use not recommended.

Renal Impairment

Assess renal function prior to initiation and periodically thereafter. Use not recommended in patients with eGFR <45 mL/minute per 1.73 m².

In a placebo-controlled trial of patients with stage 3 chronic kidney disease (eGFR ≥30 to <60 mL/minute per 1.73 m²), ertugliflozin did not demonstrate improvement in glycemic control.

Common Adverse Effects

Ertugliflozin monotherapy (≥5%): female genital mycotic infections.

Ertugliflozin in combination with metformin hydrochloride (≥5%): female genital mycotic infections, diarrhea, nausea, vomiting, flatulence, abdominal discomfort, indigestion, asthenia, headache.

Ertugliflozin in combination with sitagliptin: female genital mycotic infections, upper respiratory tract infections, nasopharyngitis, headache.

Drug Interactions

Major metabolic pathway is glucuronidation; principally glucuronidated by uridine diphosphate-glucuronosyltransferase (UGT) isoenzymes 1A9 and 2B7.

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Minimally metabolized by CYP isoenzymes. Ertugliflozin and ertugliflozin glucuronides do not inhibit CYP isoenzymes 1A2, 2B6, 2C9, 2C19, 2C8, 2D6, or 3A4 in vitro; do not induce CYP isoenzymes 1A2, 2B6, or 3A4 in vitro. Not a time-dependent inhibitor of CYP3A in vitro.

Drugs metabolized by CYP isoenzymes 1A2, 2B6, 2C9, 2C19, 2C8, 2D6, or 3A4: Pharmacokinetic interactions unlikely.

Drugs Affecting Efflux Transport Systems

Does not inhibit UGT1A6, 1A9, or 2B7 in vitro; is a weak inhibitor of UGT1A1 and 1A4. Ertugliflozin glucuronides do not inhibit UGT1A1, 1A4, 1A6, 1A9, or 2B7 in vitro. Pharmacokinetic interactions unlikely with substrates of UGT1A1, 1A4, 1A6, 1A9, or 2B7.

Not a substrate of organic anion transporters (OAT) 1 or OAT3, organic cation transporters (OCT) 1 or OCT2, or organic anion transport polypeptides (OATP) 1B1 or 1B3. Ertugliflozin and ertugliflozin glucuronides do not meaningfully inhibit OAT1, OAT3, OCT2, OATP1B1, or OATP1B3. Pharmacokinetic interactions unlikely with substrates of OAT1 or OAT3.

Substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). Ertugliflozin and ertugliflozin glucuronides do not meaningfully inhibit P-gp. Pharmacokinetic interactions unlikely with P-gp substrates.

Substrates of OCT2: Pharmacokinetic interactions unlikely.

Substrates of OATP1B1 or OATP1B3: Pharmacokinetic interactions unlikely.

Specific Drugs and Laboratory Tests

Ertugliflozin Pharmacokinetics

Absorption

Bioavailability

Absolute oral bioavailability: 100%. Peak plasma concentration attained 1 hour after oral dosing in fasted state.

Food

Administration with high-fat, high-calorie meal decreased peak plasma concentration by 29% and prolonged time to peak plasma concentration by approximately 1 hour, but did not alter AUC; not considered clinically meaningful.

Special Populations

Moderate hepatic impairment (Child-Pugh class B): AUC and peak plasma concentrations decreased by 13 and 21%, respectively; these decreases not considered clinically meaningful.

Severe hepatic impairment: Data lacking.

Mild renal impairment: AUC increased 1.6-fold compared with individuals with normal renal function.

Moderate renal impairment: AUC increased 1.7-fold compared with individuals with normal renal function.

Severe renal impairment: AUC increased 1.6-fold compared with individuals with normal renal function.

Distribution

Plasma Protein Binding

93.6%.

Special Populations

Renal or moderate hepatic impairment does not alter plasma protein binding.

Elimination

Metabolism

Metabolized principally by UGT1A9 and UGT2B7 to inactive metabolites.

Elimination Route

41 and 50% of total radioactivity excreted in urine and feces, respectively, with 1.5 and 33.8% in urine and feces, respectively, as parent drug.

Half-life

Approximately 16.6 hours.

Stability

Storage

Oral

Tablets

20–25°C (excursions permitted to 15–30°C). Protect from moisture; store in dry place.

Actions

• Inhibits SGLT2, a transporter expressed in proximal renal tubules and responsible for majority of reabsorption of filtered glucose from the tubular lumen.

• Reduces reabsorption of filtered glucose and lowers the renal threshold for glucose in a dose-dependent manner, leading to increased urinary glucose excretion.

• Increases glucose excretion independent of insulin secretion.

Advice to Patients

• Advise the patient to read the FDA-approved patient labeling (Medication Guide) before initiating therapy and each time the drug is dispensed.

• When ertugliflozin is used in fixed combination with other drugs, inform patients of other important cautionary information about the concomitant agent(s).

• Inform patients that ertugliflozin can cause potentially fatal ketoacidosis and that type 2 diabetes mellitus and pancreatic disorders (e.g., history of pancreatitis or pancreatic surgery) are risk factors. Educate all patients on precipitating factors (such as insulin dosage reduction or missed insulin doses, infection, reduced caloric intake, ketogenic diet, surgery, dehydration, and alcohol abuse) and symptoms of ketoacidosis (including nausea, vomiting, abdominal pain, tiredness, and labored breathing). Inform patients that blood glucose may be normal even in the presence of ketoacidosis. Advise patients that they may be asked to monitor ketones. If symptoms of ketoacidosis occur, instruct patients to discontinue ertugliflozin and seek medical attention immediately.

• Inform patients of the potentially increased risk of amputation with ertugliflozin therapy. Advise patients of the importance of routine preventative foot care. Advise patients to monitor for new pain, tenderness, sores or ulcers, or infections involving the leg or foot and to seek prompt medical advice if such signs or symptoms develop.

• Inform patients that symptomatic hypotension may occur with ertugliflozin and advise patients to report such symptoms to their clinicians. Inform patients that ertugliflozin-induced dehydration may increase the risk of hypotension and that patients should maintain adequate fluid intake.

• Inform patients receiving ertugliflozin of the potential for urinary tract infections, which may be serious. Advise patients of the signs and symptoms of urinary tract infection and of the need to contact a clinician if such signs and symptoms occur.

• Inform patients that the incidence of hypoglycemia may be increased if ertugliflozin is added to insulin and/or an insulin secretagogue. Educate patients on the signs and symptoms of hypoglycemia.

• Inform patients that necrotizing infections of the perineum (Fournier's gangrene) have occurred with SGLT2 inhibitor therapy. Advise patients to promptly seek medical attention if they develop pain or tenderness, redness, or swelling of the genitals or the area from the genitals back to the rectum, in addition to fever (>38°C) or malaise.

• Inform patients that yeast infection (e.g., vulvovaginitis, balanitis, balanoposthitis) may occur. Inform female patients of the signs and symptoms of vaginal yeast infections (e.g., vaginal discharge, odor, itching) and male patients of the signs and symptoms of balanitis or balanoposthitis (e.g., rash or redness of the glans or foreskin of the penis). Advise patients of treatment options and when to seek medical advice.

• Inform patients that due to the mechanism of action of ertugliflozin, patients taking the drug will test positive for glucose in their urine. Advise patients that urine glucose tests should not be used to monitor glycemic status while taking ertugliflozin.

• Inform female patients of reproductive potential of the potential risk to a fetus from ertugliflozin. Instruct patients to notify their clinician if they are or plan to become pregnant. Advise patients that ertugliflozin use is not recommended while breast-feeding.

• Advise patients of the importance of taking ertugliflozin exactly as directed by their. clinician. Advise patients that if a dose is missed, it should be taken as soon as they remember; the dose should not be doubled to make up for a missed dose.

• Inform patients of the importance of adherence to dietary instructions, regular physical activity, periodic blood glucose monitoring and glycosylated hemoglobin (hemoglobin A_1c; HbA_1c) testing, recognition and management of hypoglycemia and hyperglycemia, and assessment of diabetes mellitus complications.

• Advise patients to inform clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.

• Advise patients of other precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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