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Steglatro

Generic Name: Ertugliflozin L-pyroglutamic Acid
Class: Sodium-glucose Cotransporter 2 (SGLT2) Inhibitors
Chemical Name: (1S,2S,3S,4R,5S)-5-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-1-(hydroxymethyl)-6,8-dioxabicyclo[3.2.1]octane-2,3,4-triol with (2S)-5-oxopyrrolidine-2-carboxylic acid
Molecular Formula: C27H32ClNO10
CAS Number: 1210344-57-2

Medically reviewed by Drugs.com. Last updated on Nov 18, 2019.

Introduction

Antidiabetic agent; sodium-glucose cotransporter 2 (SGLT2) inhibitor.1 11 19

Uses for Steglatro

Type 2 Diabetes Mellitus

Used as monotherapy as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus.1 2

Used in combination with other antidiabetic agents as an adjunct to diet and exercise in patients with type 2 diabetes mellitus who have not achieved adequate glycemic control.1 3 4 5 6 7 9 10 12 13

Used in fixed combination with metformin (Segluromet) as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus who are not adequately controlled with ertugliflozin or metformin monotherapy, or in patients who are already receiving therapy with both drugs.9

Used in fixed combination with sitagliptin (Steglujan) as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus when treatment with both drugs is appropriate.10

Current guidelines for the treatment of type 2 diabetes mellitus generally recommend metformin as first-line therapy in addition to lifestyle modifications due to its well-established safety and efficacy (e.g., beneficial effects on glycosylated hemoglobin [hemoglobin A1c; HbA1c], weight, and cardiovascular mortality).598 604 Consider patient's comorbidities when selecting additional antidiabetic agents.598 604

Some SGLT2 inhibitors have shown beneficial effects on cardiovascular disease outcomes and CKD progression.604 Evidence of macrovascular risk reduction with ertugliflozin not conclusively demonstrated in clinical trials.1 9 10

Patients with type 2 diabetes mellitus who have established atherosclerotic cardiovascular disease (ASCVD) should receive a drug with demonstrated cardiovascular disease benefit (e.g., glucagon-like peptide-1 [GLP-1] receptor agonist [e.g., liraglutide], SGLT2 inhibitor [e.g., canagliflozin, empagliflozin]).604 In patients with ASCVD and heart failure or with an increased risk of heart failure, an SGLT2 inhibitor with demonstrated cardiovascular benefit may be preferred.604

In patients with type 2 diabetes mellitus and CKD, an SGLT2 inhibitor or GLP-1 receptor agonist with demonstrated ability to reduce the risk of CKD progression, cardiovascular events, or both (e.g., canagliflozin, empagliflozin, liraglutide) should be considered.604

In patients without ASCVD, heart failure, or CKD, the decision regarding the addition of other antidiabetic agents (e.g., sulfonylurea, thiazolidinedione, dipeptidyl peptidase-4 [DPP-4] inhibitor, SGLT2 inhibitor, GLP-1 receptor agonist, basal insulin) should be based on drug-specific effects and individual patient factors.604

Not indicated for type 1 diabetes mellitus or treatment of diabetic ketoacidosis.1 9 10

Steglatro Dosage and Administration

General

  • Correct volume depletion before initiating ertugliflozin therapy.1 Assess renal function prior to treatment and periodically thereafter.1

Administration

Oral Administration

Administer ertugliflozin or ertugliflozin in fixed combination with sitagliptin orally once daily in the morning, with or without food.1 10

Administer ertugliflozin in fixed combination with metformin hydrochloride orally twice daily with meals.10

Dosage

Available as ertugliflozin L-pyroglutamic acid; dosage expressed in terms of ertugliflozin.1 9 10

Adults

Type 2 Diabetes Mellitus
Ertugliflozin
Oral

Initially, 5 mg once daily.1

If well tolerated, increase dosage to 15 mg once daily in patients who require additional glycemic control.1

Ertugliflozin/Metformin Hydrochloride Fixed-combination Therapy
Oral

Initial dosage based on patient's current regimen with ertugliflozin and/or metformin hydrochloride.9 May increase dosage gradually based on effectiveness and tolerability.9

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.9

Patients currently receiving ertugliflozin: Initially, total daily dosage of 1 g of metformin hydrochloride and an ertugliflozin dosage similar to the patient's existing total daily dosage, given in 2 divided doses daily.9

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.9

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.10

If well tolerated, increase dosage to 15 mg of ertugliflozin and 100 mg of sitagliptin once daily in patients who require additional glycemic control.10

Patients currently receiving ertugliflozin: Maintain current ertugliflozin dosage with sitagliptin 100 mg once daily.10

Prescribing Limits

Adults

Type 2 Diabetes Mellitus
Ertugliflozin
Oral

Maximum 15 mg daily.1

Ertugliflozin/Metformin Hydrochloride Fixed-combination Therapy
Oral

Maximum 15 mg of ertugliflozin and 2 g of metformin hydrochloride daily (in divided doses).9

Ertugliflozin/Sitagliptin Fixed-combination Therapy
Oral

Maximum 15 mg of ertugliflozin and 100 mg of sitagliptin daily.10

Special Populations

Hepatic Impairment

Ertugliflozin Monotherapy
Oral

Mild or moderate hepatic impairment: No dosage adjustment necessary.1

Severe hepatic impairment: Data lacking on use of ertugliflozin; use not recommended.1

Ertugliflozin/Metformin Hydrochloride Fixed-combination Therapy
Oral

Use of the fixed combination of ertugliflozin and metformin hydrochloride not recommended.9

Ertugliflozin/Sitagliptin Fixed-combination Therapy
Oral

Mild or moderate hepatic impairment: No dosage adjustment necessary.10

Severe hepatic impairment: Data lacking on use of the fixed combination of ertugliflozin and sitagliptin; use not recommended.10

Renal Impairment

Ertugliflozin Monotherapy
Oral

Mild renal impairment (eGFR 60–89 mL/minute per 1.73 m2): No dosage adjustment necessary.1

Moderate renal impairment (eGFR 30 to <60 mL/minute per 1.73 m2): Do not initiate ertugliflozin.1 (See Renal Impairment under Cautions.) Continued use not recommended in patients with an eGFR persistently between 30 and <60 mL/minute per 1.73 m2.1

Severe renal impairment (eGFR <30 mL/minute per 1.73 m2): Contraindicated.1

Ertugliflozin/Metformin Hydrochloride Fixed-combination Therapy
Oral

Mild renal impairment (eGFR 60–89 mL/minute per 1.73 m2): No dosage adjustment necessary.9

Moderate renal impairment (eGFR 30 to <60 mL/minute per 1.73 m2): Do not initiate the fixed combination of ertugliflozin and metformin hydrochloride.9 Continued use not recommended in patients with an eGFR persistently between 30 and <60 mL/minute per 1.73 m2.9

Severe renal impairment (eGFR <30 mL/minute per 1.73 m2): Contraindicated.9

Ertugliflozin/Sitagliptin Fixed-combination Therapy
Oral

Mild renal impairment (eGFR 60–89 mL/minute per 1.73 m2): No dosage adjustment necessary.10

Moderate renal impairment (eGFR 30 to <60 mL/minute per 1.73 m2): Do not initiate the fixed combination of ertugliflozin and sitagliptin.10 Continued use not recommended in patients with an eGFR persistently between 30 and <60 mL/minute per 1.73 m2.10

Severe renal impairment (eGFR <30 mL/minute per 1.73 m2): Contraindicated.10

Cautions for Steglatro

Contraindications

  • History of serious hypersensitivity reaction to ertugliflozin or any ingredient in the formulation.1 9 10

  • Severe renal impairment (eGFR <30 mL/minute per 1.73 m2), end-stage renal disease (ESRD), or on dialysis.1 9 10

Warnings/Precautions

Hypotension

May cause intravascular volume contraction.1 Symptomatic hypotension can occur, particularly in patients with impaired renal function (eGFR <60 mL/minute per 1.73 m2), geriatric patients, or patients receiving diuretics.1 Assess and correct intravascular volume status prior to initiating ertugliflozin in such patients.1

Monitor patients for signs and symptoms of hypotension after initiating therapy.1

Ketoacidosis

Ketoacidosis (e.g., diabetic ketoacidosis, ketoacidosis, ketosis) requiring hospitalization reported with SGLT2 inhibitors; may occur without markedly elevated blood glucose concentrations (e.g., <250 mg/dL).1 39 40 41 42 50

Evaluate for the presence of acidosis, including ketoacidosis, in patients experiencing signs or symptoms of acidosis regardless of the patient's blood glucose concentration; discontinue SGLT2 inhibitor and initiate appropriate treatment to correct acidosis if confirmed.1 39 40 50 (See Advice to Patients.)

Prior to initiating ertugliflozin therapy, consider factors that may predispose patients to ketoacidosis (e.g., pancreatic insulin deficiency, reduced caloric intake, alcohol abuse).1 50

Consider temporarily discontinuing SGLT2 inhibitor in patients with clinical situations known to predispose to ketoacidosis (e.g., prolonged fasting due to acute illness or surgery).1 50

Some clinicians suggest monitoring of urine and/or plasma ketone levels if patients feel unwell, regardless of ambient glucose concentrations.40 42

Renal Effects

Causes intravascular volume contraction and can cause renal impairment.1 51

May increase Scr concentration and decrease eGFR; geriatric patients and patients with impaired renal function may be more susceptible to these changes.1 Adverse effects related to renal function can occur following initiation of the drug.1

Prior to initiating ertugliflozin therapy, consider factors that may predispose patients to acute kidney injury, such as hypovolemia, chronic renal insufficiency, heart failure, and concomitant medications (e.g., diuretics, ACE inhibitors, angiotensin II receptor antagonists, NSAIAs).1

Consider temporarily discontinuing ertugliflozin in any setting of reduced oral intake (e.g., acute illness, fasting) or fluid losses (e.g., GI illness, excessive heat exposure).1

Evaluate renal function prior to initiation of ertugliflozin and monitor periodically thereafter.1 Discontinue ertugliflozin and initiate appropriate treatment if kidney injury occurs.1 51

Urosepsis and Pyelonephritis

Treatment with an SGLT2 inhibitor increases the risk for urinary tract infections.1 Serious urinary tract infections (e.g., urosepsis, pyelonephritis requiring hospitalization) reported in patients receiving an SGLT2 inhibitor.1 50

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).50

Monitor patients for urinary tract infections and initiate treatment if indicated.1 50

Lower Limb Amputation

Analysis of data from clinical studies evaluating another SGLT2 inhibitor (canagliflozin) revealed a twofold increase in leg and foot amputations, mostly affecting the toes and midfoot, in patients receiving the drug.52 53 55 56

Lower limb amputations reported in 0.2 or 0.5% of patients receiving ertugliflozin 5 or 15 mg daily, respectively, compared with 0.1% of patients receiving a comparator drug during clinical trials.1

Causal association between ertugliflozin and lower limb amputation not established.1

Concomitant Therapy with Hypoglycemic Agents

When adding ertugliflozin to therapy with an insulin secretagogue (e.g., a sulfonylurea) or insulin, consider reducing dosage of the concomitant insulin secretagogue or insulin to reduce the risk of hypoglycemia.1 (See Specific Drugs and Laboratory Tests under Interactions.)

Fournier Gangrene

Fournier gangrene (necrotizing fasciitis of the perineum), a rare but serious life-threatening bacterial infection requiring urgent surgical intervention, reported during postmarketing surveillance of men and women with type 2 diabetes mellitus receiving an SGLT2 inhibitor.1 59 60 61 62

Assess patient for necrotizing fasciitis if pain or tenderness, erythema, or swelling in the genital or perineal area occurs in addition to fever or malaise.1 60

If Fournier gangrene suspected, discontinue ertugliflozin and initiate treatment immediately with broad-spectrum antibiotics and, if necessary, surgical debridement.1 60 Closely monitor blood glucose concentrations and initiate alternative antidiabetic agent to maintain glycemic control.1 60

Genital Mycotic Infections

Increases risk of genital mycotic infections in males (e.g., balanitis) and females (e.g., vulvovaginal mycotic infection).1 Patients with a history of genital mycotic infections and uncircumcised males are more likely to develop such infections.1

Monitor patients for genital mycotic infections and institute appropriate treatment if these infections occur.1

Risk of Bone Fracture

Increased risk of bone fractures and dose-related decreases in bone mineral density in older adults observed in patients receiving another SGLT2 inhibitor (canagliflozin).43

Effects on Lipoproteins

Increases in LDL-cholesterol can occur.1 Monitor serum LDL-cholesterol concentrations and treat such lipid elevations according to the standard of care.1

Use of Fixed Combinations

When ertugliflozin is used in fixed combination with metformin hydrochloride, sitagliptin, or other drugs, consider the cautions, precautions, contraindications, and interactions associated with the concomitant agent(s) in addition to those associated with ertugliflozin.1 9 10

Specific Populations

Pregnancy

Studies in animals indicate that ertugliflozin use during pregnancy may affect renal development and maturation, especially during the second and third trimesters of pregnancy.1

Limited data with ertugliflozin in pregnant women not sufficient to determine a drug-associated risk for major birth defects or miscarriage, and 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.1

Lactation

Distributed into milk in rats; not known whether distributed into human milk.1 Discontinue nursing or the drug.1

Pediatric Use

Safety and efficacy not established in pediatric patients <18 years of age.1 9 10

Geriatric Use

In clinical trials, geriatric patients receiving ertugliflozin more likely to experience certain adverse reactions related to volume depletion compared with younger patients.1

Diminished efficacy expected in geriatric patients with renal impairment.1

Hepatic Impairment

Data lacking on the use of ertugliflozin in patients with severe hepatic impairment; such use not recommended.1

Renal Impairment

Assess renal function prior to initiation of ertugliflozin therapy and periodically thereafter.1

Safety and efficacy of ertugliflozin not established in patients with moderate renal impairment (eGFR 30–59 mL/minute per 1.73 m2).1 In a clinical trial in patients with type 2 diabetes mellitus inadequately controlled on diet and exercise with or without other antidiabetic agents, the addition of ertugliflozin (5 or 15 mg once daily) to background antidiabetic agents did not improve glycemic control compared with placebo.1 8 Patients who received ertugliflozin had increased risk of renal impairment, renal-related adverse effects, and adverse effects related to volume depletion compared with placebo-treated patients.1 8

Not expected to be effective in patients with severe renal impairment (including those with ESRD or undergoing dialysis); contraindicated in such patients.1 (See Contraindications.)

Common Adverse Effects

Female genital mycotic infection,1 2 3 6 7 male genital mycotic infections,1 2 3 6 7 urinary tract infections,1 3 6 7 headache,1 vaginal pruritus,1 increased urination,1 nasopharyngitis,1 6 back pain,1 decreased weight,1 thirst.1

Interactions for Steglatro

Major metabolic pathway is glucuronidation; principally glucuronidated by uridine diphosphate-glucuronosyltransferase (UGT) isoenzymes 1A9 and 2B7.1 17

Did not inhibit UGT1A6, 1A9, or 2B7 in vitro; was a weak inhibitor of UGT1A1 and 1A4.1 Ertugliflozin glucuronides did not inhibit UGT1A1, 1A4, 1A6, 1A9, or 2B7 in vitro.1

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

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 1B3.1 Ertugliflozin and ertugliflozin glucuronides did not meaningfully inhibit OAT1, OAT3, OCT2, OATP1B1, or OATP1B3.1

Substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP).1 Ertugliflozin and ertugliflozin glucuronides did not meaningfully inhibit P-gp.1

Drugs Metabolized by Hepatic Microsomal Enzymes

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

Drugs Affected by Organic Anion Transporters

Substrates of OAT1 or OAT3: Pharmacokinetic interactions unlikely.1

Drugs Affected by Organic Cation Transporters

Substrates of OCT2: Pharmacokinetic interactions unlikely.1

Drugs Affected by P-glycoprotein Transport

P-gp substrates: Pharmacokinetic interactions unlikely.1

Drugs Affected by Uridine Diphosphate-glucuronosyltransferase

Substrates of UGT1A1, 1A4, 1A6, 1A9, or 2B7: Pharmacokinetic interactions unlikely.1

Drugs Affected by Organic Anion Transport Polypeptides

Substrates of OATP1B1 or OATP1B3: Pharmacokinetic interactions unlikely.1

Specific Drugs and Laboratory Tests

Drug or Test

Interaction

Comments

Diuretics

Possible increased incidence of symptomatic hypotension1

Assess and correct intravascular volume prior to ertugliflozin initiation; monitor for signs and symptoms of hypotension after initiating therapy1

Insulin or insulin secretagogue (e.g., sulfonylureas)

Increased risk of hypoglycemia 1

Glimepiride: No clinically important effect on pharmacokinetics of either drug1

Reduced dosage of insulin or insulin secretagogue may be required to reduce the risk of hypoglycemia1

Mefenamic acid

Increased ertugliflozin peak plasma concentration and AUC; increases not clinically relevant1

Metformin

No clinically important effect on pharmacokinetics of either drug 1

No dosage adjustment necessary1

Rifampin

Decreased ertugliflozin peak plasma concentration and AUC 1

No dosage adjustment necessary1

Simvastatin

No clinically important effect on pharmacokinetics of either drug1

No dosage adjustment necessary1

Sitagliptin

No clinically important effect on pharmacokinetics of either drug1

No dosage adjustment necessary1

Urine glucose tests (e.g., 1,5-anhydroglucitol assay)

SGLT2 inhibitors increase urinary glucose excretion and will result in false-positive urine glucose tests1

Use alternative methods to monitor glycemic control1

Steglatro Pharmacokinetics

Absorption

Bioavailability

Absolute oral bioavailability: 100%.1 Peak plasma concentration attained 1 hour after oral dosing in fasted state.1 17

Food

Administration with a 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.1 These changes not considered clinically meaningful.1

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.1

Severe hepatic impairment: Data lacking.1

Mild renal impairment: AUC increased 1.6-fold compared with individuals with normal renal function.1

Moderate renal impairment: AUC increased 1.7-fold compared with individuals with normal renal function.1

Severe renal impairment: AUC increased 1.6-fold compared with individuals with normal renal function.1

Distribution

Plasma Protein Binding

93.6%.1

Special Populations

Renal or moderate hepatic impairment does not alter plasma protein binding.1

Elimination

Metabolism

Metabolized principally by UGT1A9 and UGT2B7 to inactive metabolites.1

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.1

Half-life

Approximately 16.6 hours.1

Stability

Storage

Oral

Tablets

20–25°C (may be exposed to 15–30°C).1 Protect from moisture; store in dry place.1

Actions

  • Inhibits SGLT2, a transporter expressed in proximal renal tubules and responsible for majority of reabsorption of filtered glucose from the tubular lumen.1 11 12 13 17

  • Reduces reabsorption of filtered glucose and lowers the renal threshold for glucose in a dose-dependent manner, leading to increased urinary glucose excretion.1 11 12 13

  • Increases glucose excretion independent of insulin secretion.12

Advice to Patients

  • Importance of patient reading medication guide before initiating therapy and each time the drug is dispensed.1 9 10 14 15 16

  • Importance of informing patients of the potential risks and benefits of ertugliflozin and of alternative therapies.1

  • Importance of informing patients about the importance of adherence to dietary instructions, regular physical activity, periodic blood glucose monitoring and HbA1c testing, recognition and management of hypoglycemia and hyperglycemia, and assessment of diabetes complications.1

  • Importance of promptly seeking medical advice during periods of stress such as fever, trauma, infection, or surgery as medication requirements may change.1

  • Importance of taking ertugliflozin exactly as directed by clinician.1 Importance of advising patients about what to do if a dose of ertugliflozin is missed.1 (See Administration under Dosage and Administration.)

  • Importance of informing patients that the incidence of hypoglycemia may be increased if ertugliflozin is used concomitantly with insulin and/or an insulin secretagogue.1 Importance of informing patients that a lower dosage of insulin or insulin secretagogue may be required to reduce the risk of hypoglycemia if used concomitantly with ertugliflozin.1

  • Importance of informing patients that symptomatic hypotension may occur with ertugliflozin and to report such symptoms to their clinicians.1 Inform patients that ertugliflozin-induced dehydration may increase the risk of hypotension and that patients should maintain adequate fluid intake.1

  • Importance of informing patients that ketoacidosis, which can be a life-threatening condition, has been reported with ertugliflozin therapy.1 Importance of informing patients and their caregivers of the signs and symptoms of ketoacidosis (e.g., tachypnea or hyperventilation, anorexia, abdominal pain, nausea, vomiting, lethargy, mental status change) and of instructing patients to discontinue ertugliflozin and seek medical attention immediately should they experience any such signs or symptoms.1 39 42 50 Advise patients to use a ketone dipstick to check for ketones in their urine (when possible) if symptoms of ketoacidosis occur, even if blood glucose is not elevated (e.g., <250 mg/dL).1 50

  • Importance of informing patients that acute kidney injury has been reported with ertugliflozin therapy.1 Advise patients to seek medical advice immediately if they have reduced oral intake (such as due to acute illness or fasting) or increased fluid losses (such as due to vomiting, diarrhea, or excessive heat exposure), as it may be appropriate to temporarily discontinue ertugliflozin in those settings.1 Importance of regular renal function testing while receiving ertugliflozin.1

  • Importance of informing patients of the potential for urinary tract infections, which may be serious, with ertugliflozin therapy.1 50 Advise patients of the signs and symptoms of urinary tract infection and the need to contact a clinician if such signs and symptoms occur.1 50

  • Importance of informing patients of the potential for an increased risk of amputations with ertugliflozin therapy.1 Advise patients of the importance of routine preventative foot care.1 Advise patients to monitor for new pain, tenderness, sores or ulcers, or infections involving the leg or foot and to seek prompt medical advise if such signs or symptoms develop.1

  • Importance of informing patients that necrotizing infections of the perineum (Fournier gangrene) have occurred with SGLT2 inhibitor therapy.1 60 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.1 60

  • Importance of informing patients that yeast infection may occur (e.g., vulvovaginitis, balanitis, balanoposthitis).1 Importance of informing 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).1 Advise patients of treatment options and when to seek medical advice.1

  • Importance of informing patients that due to the mechanism of action of ertugliflozin, patients taking the drug will test positive for glucose in their urine.1 Importance of not using urine glucose tests to monitor glycemic status while taking ertugliflozin.1

  • Importance of women informing their clinicians immediately if they are or plan to become pregnant or plan to breast-feed.1 Advise patients that ertugliflozin use is not recommended while breast-feeding.1 Importance of advising pregnant women about the potential risks to the fetus if ertugliflozin is used during pregnancy.1 All women of childbearing potential should be advised to report pregnancy to their clinician as soon as possible.1 (See Pregnancy and see Lactation under Cautions.)

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

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.

Ertugliflozin L-pyroglutamic Acid

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

5 mg (of ertugliflozin)

Steglatro

Merck

15 mg (of ertugliflozin)

Steglatro

Merck

Ertugliflozin L-pyroglutamic Acid Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

2.5 mg (of ertugliflozin) with Metformin Hydrochloride 500 mg

Segluromet

Merck

2.5 mg (of ertugliflozin) with Metformin Hydrochloride 1 g

Segluromet

Merck

5 mg (of ertugliflozin) with Sitagliptin Phosphate 100 mg (of sitagliptin)

Steglujan

Merck

7.5 mg (of ertugliflozin) with Metformin Hydrochloride 500 mg

Segluromet

Merck

7.5 mg (of ertugliflozin) with Metformin Hydrochloride 1 g

Segluromet

Merck

15 mg (of ertugliflozin) with Sitagliptin Phosphate 100 mg (of sitagliptin)

Steglujan

Merck

AHFS DI Essentials™. © Copyright 2020, Selected Revisions November 18, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

References

1. Merck. Steglatro (ertugliflozin) tablets prescribing information. Whitehouse Station, NJ; 2018 Oct.

2. Terra SG, Focht K, Davies M et al. Phase III, efficacy and safety study of ertugliflozin monotherapy in people with type 2 diabetes mellitus inadequately controlled with diet and exercise alone. Diabetes Obes Metab. 2017; 19:721-728. http://www.ncbi.nlm.nih.gov/pubmed/28116776?dopt=AbstractPlus

3. Rosenstock J, Frias J, Páll D et al. Effect of ertugliflozin on glucose control, body weight, blood pressure and bone density in type 2 diabetes mellitus inadequately controlled on metformin monotherapy (VERTIS MET). Diabetes Obes Metab. 2018; 20:520-529. http://www.ncbi.nlm.nih.gov/pubmed/28857451?dopt=AbstractPlus

4. Hollander P, Liu J, Hill J et al. Ertugliflozin Compared with Glimepiride in Patients with Type 2 Diabetes Mellitus Inadequately Controlled on Metformin: The VERTIS SU Randomized Study. Diabetes Ther. 2018; 9:193-207. http://www.ncbi.nlm.nih.gov/pubmed/29282633?dopt=AbstractPlus

5. Pratley RE, Eldor R, Raji A et al. Ertugliflozin plus sitagliptin versus either individual agent over 52 weeks in patients with type 2 diabetes mellitus inadequately controlled with metformin: The VERTIS FACTORIAL randomized trial. Diabetes Obes Metab. 2018; 20:1111-1120. http://www.ncbi.nlm.nih.gov/pubmed/29266675?dopt=AbstractPlus

6. Dagogo-Jack S, Liu J, Eldor R et al. Efficacy and safety of the addition of ertugliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin and sitagliptin: The VERTIS SITA2 placebo-controlled randomized study. Diabetes Obes Metab. 2018; 20:530-540. http://www.ncbi.nlm.nih.gov/pubmed/28921862?dopt=AbstractPlus

7. Miller S, Krumins T, Zhou H et al. Ertugliflozin and Sitagliptin Co-initiation in Patients with Type 2 Diabetes: The VERTIS SITA Randomized Study. Diabetes Ther. 2018; 9:253-268. http://www.ncbi.nlm.nih.gov/pubmed/29313282?dopt=AbstractPlus

8. Grunberger G, Camp S, Johnson J et al. Ertugliflozin in Patients with Stage 3 Chronic Kidney Disease and Type 2 Diabetes Mellitus: The VERTIS RENAL Randomized Study. Diabetes Ther. 2018; 9:49-66. http://www.ncbi.nlm.nih.gov/pubmed/29159457?dopt=AbstractPlus

9. Merck. Segluromet (ertugliflozin and metformin hydrochloride) tablets prescribing information. Whitehouse Station, NJ; 2018 Oct.

10. Merck. Steglujan (ertugliflozin and sitagliptin) tablets prescribing information. Whitehouse Station, NJ; 2018 Oct.

11. Cinti F, Moffa S, Impronta F et al. Spotlight on ertugliflozin and its potential in the treatment of type 2 diabetes: evidence to date. Drug Des Devel Ther. 2017; 11:2905-2919. http://www.ncbi.nlm.nih.gov/pubmed/29042751?dopt=AbstractPlus

12. Riser Taylor S, Harris KB. The clinical efficacy and safety of sodium glucose cotransporter-2 inhibitors in adults with type 2 diabetes mellitus. Pharmacotherapy. 2013; 33:984-99. http://www.ncbi.nlm.nih.gov/pubmed/23744749?dopt=AbstractPlus

13. US Food and Drug Administration. Center for Drug Evaluation and Research: Application number 209803Orig1s000, 209805Orig1s000, 209806Orig1s000: Clinical pharmacology and biopharmaceutics review(s). From FDA website. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209803,209805,209806Orig1s000ClinPharmR.pdf

14. Merck. Segluromet (ertugliflozin and metformin hydrochloride) tablets medication guide. Whitehouse Station, NJ; 2018 Oct.

15. Merck. Steglujan (ertugliflozin and sitagliptin) tablets medication guide. Whitehouse Station, NJ; 2018 Oct.

16. Merck. Steglatro (ertugliflozin) tablets medication guide. Whitehouse Station, NJ; 2018 Oct.

17. Miao Z, Nucci G, Amin N et al. Pharmacokinetics, metabolism, and excretion of the antidiabetic agent ertugliflozin (PF-04971729) in healthy male subjects. Drug Metab Dispos. 2013; 41:445-56. http://www.ncbi.nlm.nih.gov/pubmed/23169609?dopt=AbstractPlus

18. Sahasrabudhe V, Terra SG, Hickman A et al. The Effect of Renal Impairment on the Pharmacokinetics and Pharmacodynamics of Ertugliflozin in Subjects With Type 2 Diabetes Mellitus. J Clin Pharmacol. 2017; 57:1432-1443. http://www.ncbi.nlm.nih.gov/pubmed/28703316?dopt=AbstractPlus

19. . Ertugliflozin for type 2 diabetes. Med Lett Drugs Ther. 2018; 60:70-72. http://www.ncbi.nlm.nih.gov/pubmed/29667948?dopt=AbstractPlus

39. US Food and Drug Administration. FDA Drug Safety Communication: FDA warns that SGLT2 inhibitors for diabetes may result in a serious condition of too much acid in the blood. 2015 May 15. From FDA website. Accessed 2015 July 6. http://www.fda.gov/downloads/Drugs/DrugSafety/UCM446954.pdf

40. Rosenstock J, Ferrannini E. Euglycemic diabetic ketoacidosis: a predictable, detectable, and preventable safety concern with SGLT2 inhibitors. Diabetes Care. 2015; 38:1638-42. http://www.ncbi.nlm.nih.gov/pubmed/26294774?dopt=AbstractPlus

41. Erondu N, Desai M, Ways K et al. Diabetic ketoacidosis and related events in the canagliflozin type 2 diabetes clinical program. Diabetes Care. 2015; 38:1680-6. http://www.ncbi.nlm.nih.gov/pubmed/26203064?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=4542268&blobtype=pdf

42. Peters AL, Buschur EO, Buse JB et al. Euglycemic diabetic ketoacidosis: a potential complication of treatment with sodium–glucose cotransporter 2 inhibition. Diabetes Care. 2015; 38:1687–93. http://www.ncbi.nlm.nih.gov/pubmed/26078479?dopt=AbstractPlus

43. Buse JB, Vilsbøll T, Thurman J et al. Contribution of liraglutide in the fixed-ratio combination of insulin degludec and liraglutide (IDegLira). Diabetes Care. 2014; 37:2926-33. http://www.ncbi.nlm.nih.gov/pubmed/25114296?dopt=AbstractPlus

50. US Food and Drug Administration. FDA Drug Safety Communication: FDA revises labels of SGLT2 inhibitors for diabetes to include warnings about too much acid in the blood and serious urinary tract infections. From FDA website. http://www.fda.gov/downloads/Drugs/DrugSafety/UCM475487.pdf

51. US Food and Drug Administration. FDA Drug Safety Communication: FDA strengthens kidney warnings for diabetes medicine canagliflozin (Invokana, Invokamet) and dapagliflozin (Farxiga, Xigduo XR). From FDA website. http://www.fda.gov/downloads/Drugs/DrugSafety/UCM506772.pdf

52. US Food and Drug Administration. FDA Drug Safety Communication: Interim clinical trial results find increased risk of leg and foot amputations, mostly affecting the toes, with the diabetes medicine canagliflozin (Invokana, Invokamet); FDA to investigate. From FDA website. http://www.fda.gov/downloads/Drugs/DrugSafety/UCM501749.pdf

53. Neal B, Perkovic V, de Zeeuw D et al. Rationale, design, and baseline characteristics of the Canagliflozin Cardiovascular Assessment Study (CANVAS)--a randomized placebo-controlled trial. Am Heart J. 2013; 166:217-223.e11. http://www.ncbi.nlm.nih.gov/pubmed/23895803?dopt=AbstractPlus

55. US Food and Drug Administration. FDA Drug Safety Communication: FDA confirms increased risk of leg and foot amputations with the diabetes medicine canagliflozin (Invokana, Invokamet, Invokamet XR). From FDA website. https://www.fda.gov/downloads/Drugs/DrugSafety/UCM558427.pdf

56. Neal B, Perkovic V, Mahaffey KW et al. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med. 2017;

59. Bersoff-Matcha SJ, Chamberlain C, Cao C et al. Fournier gangrene associated with sodium-glucose cotransporter-2 inhibitors: a review of spontaneous postmarketing cases. Ann Intern Med. 2019; http://www.ncbi.nlm.nih.gov/pubmed/31060053?dopt=AbstractPlus

60. US Food and Drug Administration. FDA Drug Safety Communication: FDA warns about rare occurrences of a serious infection of the genital area with SGLT2 inhibitors for diabetes. Silver Spring, MD; 2018 Aug 29. From FDA website. https://www.fda.gov/downloads/Drugs/DrugSafety/UCM618466.pdf

61. Cecilia-Chi W, Lim-Tio S. Fournier's syndrome: a life-threatening complication of SGLT2 inhibition in poorly controlled diabetes mellitus. 2016 Joint Annual Scientific Meeting of the Australian Diabetes Educators Association (ADEA) and Australian Diabetes Society (ADS). Abstract number 265.

62. Kumar S, Costello AJ, Colman PG. Fournier's gangrene in a man on empagliflozin for treatment of Type 2 diabetes. Diabet Med. 2017; 34:1646-1648. http://www.ncbi.nlm.nih.gov/pubmed/28887847?dopt=AbstractPlus

84. Trujillo JM, Nuffer WA. Impact of sodium-glucose cotransporter 2 inhibitors on nonglycemic outcomes in patients with type 2 diabetes. Pharmacotherapy. 2017; 37:481-491. http://www.ncbi.nlm.nih.gov/pubmed/28102030?dopt=AbstractPlus

85. Inzucchi SE, Zinman B, Wanner C et al. SGLT-2 inhibitors and cardiovascular risk: proposed pathways and review of ongoing outcome trials. Diab Vasc Dis Res. 2015; 12:90-100. http://www.ncbi.nlm.nih.gov/pubmed/25589482?dopt=AbstractPlus

598. Garber AJ, Abrahamson MJ, Barzilay JI et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endorinology on the comprehensive type 2 diabetes management algorithm - 2019 executive summary. Endocr Pract. 2019; 25:69-100. http://www.ncbi.nlm.nih.gov/pubmed/30742570?dopt=AbstractPlus

604. American Diabetes Association. 9. Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes-2019. Diabetes Care. 2019; 42:S90-S102. http://www.ncbi.nlm.nih.gov/pubmed/30559235?dopt=AbstractPlus

606. American Diabetes Association. 11. Microvascular complications and foot care: standards of medical care in diabetes-2019. Diabetes Care. 2019; 42:S124-S138. http://www.ncbi.nlm.nih.gov/pubmed/30559237?dopt=AbstractPlus

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