Steglujan

ertugliflozin and sitagliptin · Tablet, Film Coated · Oral

Prescription (Rx) Dipeptidyl Peptidase 4 Inhibitor

Uses

1 INDICATIONS AND USAGE STEGLUJAN ® is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Limitations of Use Not recommended for use to improve glycemic control in patients with type 1 diabetes mellitus [see Warnings and Precautions (5.1) ]. Has not been studied in patients with a history of pancreatitis. It is unknown whether patients with a history of pancreatitis are at increased risk for the development of pancreatitis while using STEGLUJAN [see Warnings and Precautions (5.2) ] . STEGLUJAN is a combination of ertugliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, and sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Limitations of Use: Not recommended for use to improve glycemic control in patients with type 1 diabetes mellitus. ( 1 ) Has not been studied in patients with a history of pancreatitis. ( 1 , 5.2 )

Dosage and administration

Assess renal function before initiating and as clinically indicated. ( 2.1 ) Correct volume depletion before initiating. ( 2.1 ) Recommended starting dosage is 5 mg ertugliflozin/100 mg sitagliptin orally once daily, taken in the morning, with or without food. ( 2.2 ) Increase dosage to 15 mg ertugliflozin/100 mg sitagliptin orally once daily in those tolerating STEGLUJAN and needing additional glycemic control. ( 2.2 ) Use is not recommended in patients with an estimated glomerular filtration rate (eGFR) less than 45 mL/min/1.73 m 2 . ( 2.2 ) Withhold STEGLUJAN for at least 4 days, if possible, prior to surgery or procedures associated with prolonged fasting. ( 2.3 ) 2.1 Prior to Initiation of STEGLUJAN Assess renal function before initiating STEGLUJAN and as clinically indicated [see Warnings and Precautions (5.4) ] . Assess volume status. In patients with volume depletion, correct this condition before initiating STEGLUJAN [see Warnings and Precautions (5.5) and Use in Specific Populations (8.5 , 8.6) ]. 2.2 Recommended Dosage The recommended starting dosage of STEGLUJAN is 5 mg ertugliflozin/100 mg sitagliptin orally once daily, taken in the morning, with or without food. For patients treated with ertugliflozin who are being switched to STEGLUJAN, the dosage of ertugliflozin can be maintained. For additional glycemic control, the dosage may be increased to 15 mg ertugliflozin/100 mg sitagliptin orally once daily in patients tolerating STEGLUJAN. Use is not recommended in patients with an estimated glomerular filtration rate (eGFR) less than 45 mL/min/1.73 m 2 . Use of STEGLUJAN is contraindicated in patients with severe renal impairment (eGFR less than 30 mL/min/1.73 m 2 ), end-stage renal disease (ESRD) or on dialysis [see Contraindications (4) ] . 2.3 Temporary Interruption for Surgery Withhold STEGLUJAN for at least 4 days, if possible, prior to surgery or procedures associated with prolonged fasting. Resume STEGLUJAN when the patient is clinically stable and has resumed oral intake [see Warnings and Precautions (5.1) and Clinical Pharmacology (12.2) ]. 2.4 Recommendations Regarding Missed Dose If a dose is missed, instruct patients to take the dose as soon as possible. Advise patients not to double up the next dose.

Dosage forms and strengths

5 mg/100 mg tablets: contain ertugliflozin 5 mg and sitagliptin 100 mg and are beige, almond-shaped debossed with "554" on one side and plain on the other side. STEGLUJAN 15 mg/100 mg tablets: contain ertugliflozin 15 mg and sitagliptin 100 mg and are brown, almond-shaped debossed with "555" on one side and plain on the other side. Tablets: Ertugliflozin 5 mg and sitagliptin 100 mg ( 3 ) Ertugliflozin 15 mg and sitagliptin 100 mg ( 3 )

Contraindications

4 CONTRAINDICATIONS STEGLUJAN is contraindicated in patients with: Severe renal impairment (eGFR less than 30 mL/min/1.73 m 2 ), end-stage renal disease (ESRD), or on dialysis [see Warnings and Precautions (5.4) and Use in Specific Populations (8.6) ] . Hypersensitivity to sitagliptin, ertugliflozin, or any excipient, in STEGLUJAN. Reactions such as anaphylaxis or angioedema have occurred [see Warnings and Precautions (5.9) and Adverse Reactions (6.2) ]. Severe renal impairment (eGFR less than 30 mL/min/1.73 m 2 ), end-stage renal disease, or dialysis. ( 4 ) Hypersensitivity to sitagliptin, ertugliflozin, or any excipient in STEGLUJAN. ( 4 , 5.9 , 6.2 )

Warnings and precautions

Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis: Consider ketone monitoring in patients at risk for ketoacidosis, as indicated. Assess for ketoacidosis regardless of presenting blood glucose levels and discontinue STEGLUJAN if ketoacidosis is suspected. Monitor patients for resolution of ketoacidosis before restarting. ( 5.1 ) Pancreatitis: There have been postmarketing reports of acute pancreatitis in patients taking sitagliptin, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis. If pancreatitis is suspected, promptly discontinue. ( 5.2 ) Lower Limb Amputation: Monitor patients for infections or ulcers of lower limbs, and institute appropriate treatment. ( 5.3 ) Acute Renal Failure: There have been postmarketing reports of acute renal failure in patients taking sitagliptin, sometimes requiring dialysis. Monitor renal function. ( 5.4 ) Volume Depletion: May result in acute kidney injury. Before initiating, assess and correct volume status in patients with renal impairment, or low systolic blood pressure elderly patients, or patients on diuretics. Monitor for signs and symptoms during therapy. ( 5.5 ) Genitourinary Infections, including Urosepsis, Pyelonephritis, Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene), and Genital Mycotic Infections: Monitor patients for signs and symptoms of genitourinary infections and treat promptly, if indicated. Immediately evaluate patients presenting with pain or tenderness, erythema, or swelling in the genital or perineal area, along with fever or malaise, for necrotizing fasciitis and if suspected, discontinue STEGLUJAN, and promptly institute appropriate medical and/or surgical intervention. ( 5.6 ) Heart Failure: Heart failure has been observed with two other members of the DPP-4 inhibitor class. Consider risks and benefits in patients who have known risk factors for heart failure. Monitor patients for signs and symptoms. ( 5.7 ) Hypoglycemia: Consider a lower dose of insulin or insulin secretagogue to reduce risk of hypoglycemia when used in combination. ( 5.8 ) Hypersensitivity: There have been postmarketing reports of serious allergic and hypersensitivity reactions in patients treated with sitagliptin such as anaphylaxis, angioedema, and exfoliative skin conditions including Stevens-Johnson syndrome. In such cases, promptly discontinue, assess for other potential causes, institute appropriate monitoring and treatment, and initiate alternative treatment for diabetes. ( 5.9 ) Severe and Disabling Arthralgia: Severe and disabling arthralgia has been reported in patients taking DPP-4 inhibitors. Consider as a possible cause for severe joint pain and discontinue if appropriate. ( 5.10 ) Pemphigoid: There have been postmarketing reports of bullous pemphigoid requiring hospitalization in patients taking DPP-4 inhibitors. Tell patients to report development of blisters or erosions. If bullous pemphigoid is suspected, discontinue. ( 5.11 ) 5.1 Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis In patients with type 1 diabetes mellitus, STEGLUJAN significantly increases the risk of diabetic ketoacidosis, a life-threatening event, beyond the background rate. In placebo-controlled trials of patients with type 1 diabetes mellitus, the risk of ketoacidosis was markedly increased in patients who received sodium glucose transporter 2 (SGLT2) inhibitors compared to patients who received placebo; this risk may be greater with higher doses. STEGLUJAN is not indicated for glycemic control in patients with type 1 diabetes mellitus. Type 2 diabetes mellitus and pancreatic disorders (e.g., history of pancreatitis or pancreatic surgery) are also risk factors for ketoacidosis. There have been postmarketing reports of fatal events of ketoacidosis in patients with type 2 diabetes mellitus using SGLT2 inhibitors. Precipitating conditions for diabetic ketoacidosis or other ketoacidosis include under-insulinization due to insulin dose reduction or missed insulin doses, acute febrile illness, reduced caloric intake, ketogenic diet, surgery, volume depletion, and alcohol abuse. Signs and symptoms are consistent with dehydration and severe metabolic acidosis and include nausea, vomiting, abdominal pain, generalized malaise, and shortness of breath. Blood glucose levels at presentation may be below those typically expected for diabetic ketoacidosis (e.g., less than 250 mg/dL). Ketoacidosis and glucosuria may persist longer than typically expected. Urinary glucose excretion persists for 4 days after discontinuing STEGLUJAN [see Clinical Pharmacology (12.2) ]; however, there have been postmarketing reports of ketoacidosis and/or glucosuria lasting greater than 6 days and some up to 2 weeks after discontinuation of SGLT2 inhibitors. Consider ketone monitoring in patients at risk for ketoacidosis if indicated by the clinical situation. Assess for ketoacidosis regardless of presenting blood glucose levels in patients who present with signs and symptoms consistent with severe metabolic acidosis. If ketoacidosis is suspected, discontinue STEGLUJAN, promptly evaluate, and treat ketoacidosis, if confirmed. Monitor patients for resolution of ketoacidosis before restarting STEGLUJAN. Withhold STEGLUJAN, if possible, in temporary clinical situations that could predispose patients to ketoacidosis. Resume STEGLUJAN when the patient is clinically stable and has resumed oral intake [see Dosage and Administration (2.3) ]. Educate all patients on the signs and symptoms of ketoacidosis and instruct patients to discontinue STEGLUJAN and seek medical attention immediately if signs and symptoms occur. 5.2 Pancreatitis There have been postmarketing reports of acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, in patients taking sitagliptin, a component of STEGLUJAN.

Side effects

The following important adverse reactions are described elsewhere in the labeling: Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis [see Warnings and Precautions (5.1) ] Pancreatitis [see Warnings and Precautions (5.2) ] Lower Limb Amputation [see Warnings and Precautions (5.3) ] Acute Renal Failure [see Warnings and Precautions (5.4) ] Volume Depletion [see Warnings and Precautions (5.5) ] Genitourinary Infections, including Urosepsis, Pyelonephritis, Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene), and Genital Mycotic Infections [see Warnings and Precautions (5.6) ] Heart Failure [see Warnings and Precautions (5.7) ] Hypoglycemia with Concomitant Use with Insulin or Insulin Secretagogues [see Warnings and Precautions (5.8) ] Hypersensitivity Reactions [see Warnings and Precautions (5.9) ] Severe and Disabling Arthralgia [see Warnings and Precautions (5.10) ] Bullous Pemphigoid [see Warnings and Precautions (5.11) ] Most common adverse reactions associated with ertugliflozin (incidence ≥5%): female genital mycotic infections. ( 6.1 ) Most common adverse reactions associated with sitagliptin (incidence ≥5%): upper respiratory tract infection, nasopharyngitis and headache. In the add-on to sulfonylurea and add-on to insulin studies, hypoglycemia was also more commonly reported in patients treated with sitagliptin compared to placebo. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Merck Sharp & Dohme LLC at 1-877-888-4231 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Ertugliflozin and Sitagliptin The safety of concomitantly administered ertugliflozin and sitagliptin has been evaluated in 990 patients with type 2 diabetes mellitus treated for 26 weeks in three studies; a factorial study of ertugliflozin 5 mg or 15 mg in combination with sitagliptin 100 mg once daily compared to the individual components, a placebo-controlled study of ertugliflozin 5 mg or 15 mg as add-on therapy to sitagliptin 100 mg and metformin HCl once daily, and a placebo-controlled study of initial therapy with ertugliflozin 5 mg or 15 mg once daily in combination with sitagliptin 100 mg once daily [see Clinical Studies (14) ] . The incidence and type of adverse reactions in these three studies were similar to the adverse reactions seen with ertugliflozin and described below in Table 1 . Ertugliflozin Pool of Placebo-Controlled Trials The data in Table 1 are derived from a pool of three 26-week, placebo-controlled trials. Ertugliflozin was used as monotherapy in one trial and as add-on therapy in two trials [see Clinical Studies (14) ] . These data reflect exposure of 1,029 patients to ertugliflozin with a mean exposure duration of approximately 25 weeks. Patients received ertugliflozin 5 mg (N=519), ertugliflozin 15 mg (N=510), or placebo (N=515) once daily. The mean age of the population was 57 years and 2% were older than 75 years of age. Fifty-three percent (53%) of the population was male and 73% were White, 15% were Asian, and 7% were Black or African American. At baseline the population had diabetes for an average of 7.5 years, had a mean HbA1c of 8.1%, and 19.4% had established microvascular complications of diabetes. Baseline renal function (mean eGFR 88.9 mL/min/1.73 m 2 ) was normal or mildly impaired in 97% of patients and moderately impaired in 3% of patients. Table 1 shows common adverse reactions associated with the use of ertugliflozin. These adverse reactions were not present at baseline, occurred more commonly on ertugliflozin than on placebo, and occurred in at least 2% of patients treated with either ertugliflozin 5 mg or ertugliflozin 15 mg. Table 1: Adverse Reactions Reported in ≥2% of Patients with Type 2 Diabetes Mellitus Treated with Ertugliflozin The three placebo controlled studies included one monotherapy trial and two add-on combination trials with metformin HCl or with metformin HCl and sitagliptin. and Greater than Placebo in Pooled Placebo-Controlled Clinical Studies of Ertugliflozin Monotherapy or Combination Therapy Number (%) of Patients Placebo N = 515 Ertugliflozin 5 mg N = 519 Ertugliflozin 15 mg N = 510 Female genital mycotic infections Includes: genital candidiasis, genital infection fungal, vaginal infection, vulvitis, vulvovaginal candidiasis, vulvovaginal mycotic infection, and vulvovaginitis. Percentages calculated with the number of female patients in each group as denominator: placebo (N=235), ertugliflozin 5 mg (N=252), ertugliflozin 15 mg (N=245). 3.0% 9.1% 12.2% Male genital mycotic infections Includes: balanitis candida, balanoposthitis, genital infection, and genital infection fungal. Percentages calculated with the number of male patients in each group as denominator: placebo (N=280), ertugliflozin 5 mg (N=267), ertugliflozin 15 mg (N=265). 0.4% 3.7% 4.2% Urinary tract infections Includes: cystitis, dysuria, streptococcal urinary tract infection, urethritis, urinary tract infection. 3.9% 4.0% 4.1% Headache 2.3% 3.5% 2.9% Vaginal pruritus Includes: vulvovaginal pruritus and pruritus genital. Percentages calculated with the number of female patients in each group as denominator: placebo (N=235), ertugliflozin 5 mg (N=252), ertugliflozin 15 mg (N=245). 0.4% 2.8% 2.4% Increased urination Includes: pollakiuria, micturition urgency, polyuria, urine output increased, and nocturia. 1.0% 2.7% 2.4% Nasopharyngitis 2.3% 2.5% 2.0% Back pain 2.3% 1.7% 2.5% Weight decreased 1.0% 1.2% 2.4% Thirst Includes: thirst, dry mouth, polydipsia, and dry throat.

Drug interactions

Table 3: Clinically Significant Drug Interactions with STEGLUJAN Insulin or Insulin Secretagogues Clinical Impact: The risk of hypoglycemia is increased when STEGLUJAN is used in combination with insulin or an insulin secretagogue. Intervention: A lower dose of insulin or insulin secretagogue may be required to minimize the risk of hypoglycemia when used in combination with STEGLUJAN. Lithium Clinical Impact: Concomitant use of an SGLT2 inhibitor with lithium may decrease serum lithium concentrations. Intervention: Monitor serum lithium concentration more frequently during STEGLUJAN initiation and dosage changes. Positive Urine Glucose Test Clinical Impact: SGLT2 inhibitors increase urinary glucose excretion and will lead to positive urine glucose tests. Intervention: Monitoring glycemic control with urine glucose tests is not recommended in patients taking SGLT2 inhibitors. Use alternative methods to monitor glycemic control. Interference with 1,5-anhydroglucitol (1,5-AG) Assay Clinical Impact: Measurements of 1,5-AG are unreliable in assessing glycemic control in patients taking SGLT2 inhibitors. Intervention: Monitoring glycemic control with 1,5-AG assay is not recommended. Use alternative methods to monitor glycemic control. See full prescribing information for information on drug interactions and interference of STEGLUJAN with laboratory tests. ( 7 )

Use in specific populations

Pregnancy: Advise females of the potential risk to a fetus especially during the second and third trimesters. ( 8.1 ) Lactation: Breastfeeding not recommended. ( 8.2 ) Geriatrics: Higher incidence of adverse reactions related to reduced intravascular volume. ( 8.5 ) Renal Impairment: Higher incidence of adverse reactions related to reduced intravascular volume and renal function. ( 8.6 ) 8.1 Pregnancy Risk Summary Based on animal data showing adverse renal effects, from ertugliflozin, STEGLUJAN is not recommended during the second and third trimesters of pregnancy. The limited available data with ertugliflozin and sitagliptin use during pregnancy are not sufficient to determine a drug associated risk of adverse developmental outcomes. There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy (see Clinical Considerations ) . In animal studies, adverse renal changes were observed in rats when ertugliflozin was administered during a period of renal development corresponding to the late second and third trimesters of human pregnancy. Doses approximately 13 times the maximum clinical dose caused renal pelvic and tubule dilatations and renal mineralization that were not fully reversible. There was no evidence of fetal harm in rats or rabbits at exposures of ertugliflozin approximately 300 times higher than the maximal clinical dose of 15 mg/day when administered during organogenesis (see Data ) . In rats and rabbits, sitagliptin doses of 250 and 125 mg/kg, respectively (approximately 30 and 20 times the human exposure at the maximum recommended human dose) did not adversely affect development outcomes of either species. The estimated background risk of major birth defects is 6-10% in women with pre-gestational diabetes with a HbA1c >7 and has been reported to be as high as 20-25% in women with HbA1c >10. The estimated background risk of miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity. Data Animal Data Ertugliflozin When ertugliflozin was orally administered to juvenile rats from PND 21 to PND 90, increased kidney weight, renal tubule and renal pelvis dilatation, and renal mineralization occurred at doses greater than or equal to 5 mg/kg (13-fold human exposures, based on AUC). These effects occurred with drug exposure during periods of renal development in rats that correspond to the late second and third trimester of human renal development, and did not fully reverse within a 1-month recovery period. In embryo-fetal development studies, ertugliflozin (50, 100 and 250 mg/kg/day) was administered orally to rats on gestation days 6 to 17 and to rabbits on gestation days 7 to 19. Ertugliflozin did not adversely affect developmental outcomes in rats and rabbits at maternal exposures that were approximately 300 times the human exposure at the maximum clinical dose of 15 mg/day, based on AUC. A maternally toxic dose (250 mg/kg/day) in rats (707 times the clinical dose) was associated with reduced fetal viability, and a higher incidence of a visceral malformation (membranous ventricular septal defect). In the pre- and post-natal development study in pregnant rats, ertugliflozin was administered to the dams from gestation day 6 through lactation day 21 (weaning). Decreased post-natal growth (weight gain) was observed at maternal doses ≥100 mg/kg/day (greater than or equal to 331 times the human exposure at the maximum clinical dose of 15 mg/day, based on AUC). Sitagliptin Sitagliptin administered to pregnant female rats and rabbits from gestation day 6 to 20 (organogenesis) did not adversely affect developmental outcomes at oral doses up to 250 mg/kg (rats) and 125 mg/kg (rabbits), or approximately 30 and 20 times human exposure at the maximum recommended human dose (MRHD) of 100 mg/day based on AUC comparisons. Higher doses increased the incidence of rib malformations in offspring at 1,000 mg/kg, or approximately 100 times human exposure at the MRHD. Sitagliptin administered to female rats from gestation day 6 to lactation day 21 decreased body weight in male and female offspring at 1,000 mg/kg. No functional or behavioral toxicity was observed in offspring of rats. Placental transfer of sitagliptin administered to pregnant rats was approximately 45% at 2 hours and 80% at 24 hours postdose. Placental transfer of sitagliptin administered to pregnant rabbits was approximately 66% at 2 hours and 30% at 24 hours. 8.2 Lactation Risk Summary There is no information regarding the presence of STEGLUJAN, in human milk, the effects on the breastfed infant, or the effects on milk production. Ertugliflozin and sitagliptin are present in the milk of lactating rats (see Data ) . Since human kidney maturation occurs in utero and during the first 2 years of life when lactational exposure may occur, there may be risk to the developing human kidney, based on data with ertugliflozin. Because of the potential for serious adverse reactions in a breastfed infant, advise women that the use of STEGLUJAN is not recommended while breastfeeding. Data Ertugliflozin The lacteal excretion of radiolabeled ertugliflozin in lactating rats was evaluated 10 to 12 days after parturition. Ertugliflozin-derived radioactivity exposure in milk and plasma were similar, with a milk/plasma ratio of 1.07, based on AUC.

Pregnancy

8.1 Pregnancy Risk Summary Based on animal data showing adverse renal effects, from ertugliflozin, STEGLUJAN is not recommended during the second and third trimesters of pregnancy. The limited available data with ertugliflozin and sitagliptin use during pregnancy are not sufficient to determine a drug associated risk of adverse developmental outcomes. There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy (see Clinical Considerations ) . In animal studies, adverse renal changes were observed in rats when ertugliflozin was administered during a period of renal development corresponding to the late second and third trimesters of human pregnancy. Doses approximately 13 times the maximum clinical dose caused renal pelvic and tubule dilatations and renal mineralization that were not fully reversible. There was no evidence of fetal harm in rats or rabbits at exposures of ertugliflozin approximately 300 times higher than the maximal clinical dose of 15 mg/day when administered during organogenesis (see Data ) . In rats and rabbits, sitagliptin doses of 250 and 125 mg/kg, respectively (approximately 30 and 20 times the human exposure at the maximum recommended human dose) did not adversely affect development outcomes of either species. The estimated background risk of major birth defects is 6-10% in women with pre-gestational diabetes with a HbA1c >7 and has been reported to be as high as 20-25% in women with HbA1c >10. The estimated background risk of miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Pediatric use

8.4 Pediatric Use Safety and effectiveness of STEGLUJAN in pediatric patients under 18 years of age have not been established.

Geriatric use

8.5 Geriatric Use STEGLUJAN No dosage adjustment of STEGLUJAN is recommended based on age. Elderly patients are more likely to have decreased renal function. Because renal function abnormalities can occur after initiating ertugliflozin, and sitagliptin is known to be substantially excreted by the kidneys, renal function should be assessed more frequently in elderly patients [see Dosage and Administration (2.1) and Warnings and Precautions (5.4) ] . Ertugliflozin In ertugliflozin clinical trials, a total of 876 (25.7%) patients treated with ertugliflozin were 65 years and older, and 152 (4.5%) patients treated with ertugliflozin were 75 years and older. Patients 65 years and older had a higher incidence of adverse reactions related to volume depletion compared to younger patients; events were reported in 1.1%, 2.2%, and 2.6% of patients treated with comparator, ertugliflozin 5 mg, and ertugliflozin 15 mg, respectively [see Warnings and Precautions (5.5) and Adverse Reactions (6.1) ] . In VERTIS CV, a total of 2780 (50.5%) patients treated with ertugliflozin were 65 years and older, and 595 (10.8%) patients treated with ertugliflozin were 75 years and older. Safety and efficacy were generally similar for patients age 65 years and older compared to patients younger than 65. Sitagliptin Of the total number of subjects (N=3,884) in pre-approval clinical safety and efficacy studies of sitagliptin, 725 patients were 65 years and over, while 61 patients were 75 years and over. No overall differences in safety or effectiveness were observed between subjects 65 years and over and younger subjects. While this and other reported clinical experience have not identified differences in responses between the elderly and younger patients, greater sensitivity of some older individuals cannot be ruled out.

Overdosage

In the event of an overdose with STEGLUJAN, contact the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdosage management recommendations. Employ the usual supportive measures as dictated by the patient's clinical status. Ertugliflozin Removal of ertugliflozin by hemodialysis has not been studied. Sitagliptin In the event of an overdose, it is reasonable to employ the usual supportive measures, e.g., remove unabsorbed material from the gastrointestinal tract, employ clinical monitoring (including obtaining an electrocardiogram), and institute supportive therapy as dictated by the patient's clinical status. Sitagliptin is modestly dialyzable. In clinical studies, approximately 13.5% of the dose was removed over a 3- to 4-hour hemodialysis session. Prolonged hemodialysis may be considered if clinically appropriate. It is not known if sitagliptin is dialyzable by peritoneal dialysis.

Description

(ertugliflozin and sitagliptin) tablet for oral use contains ertugliflozin L-pyroglutamic acid, a SGLT2 inhibitor, and sitagliptin phosphate, a DPP-4 inhibitor. Ertugliflozin The chemical name of ertugliflozin L-pyroglutamic acid is (1 S ,2 S ,3 S ,4 R ,5 S )-5-(4-chloro-3-(4-ethoxybenzyl)phenyl)-1-(hydroxymethyl)-6,8-dioxabicyclo[3.2.1]octane-2,3,4-triol, compound with (2 S )-5-oxopyrrolidine-2-carboxylic acid. The molecular formula is C 27 H 32 ClNO 10 and the molecular weight is 566.00. The chemical structure is: Ertugliflozin L-pyroglutamic acid is a white to off-white powder that is soluble in ethyl alcohol and acetone, slightly soluble in ethyl acetate and acetonitrile and very slightly soluble in water. Sitagliptin Sitagliptin phosphate monohydrate is described chemically as 7-[(3 R )-3-amino-1-oxo-4-(2,4,5-trifluorophenyl)butyl]-5,6,7,8-tetrahydro-3-(trifluoromethyl)-1,2,4-triazolo[4,3- a ]pyrazine phosphate (1:1) monohydrate. The empirical formula is C 16 H 15 F 6 N 5 O∙H 3 PO 4 ∙H 2 O and the molecular weight is 523.32. The structural formula is: Sitagliptin phosphate monohydrate is a white to off-white, crystalline, non-hygroscopic powder. It is soluble in water and N,N-dimethyl formamide; slightly soluble in methanol; very slightly soluble in ethanol, acetone, and acetonitrile; and insoluble in isopropanol and isopropyl acetate. STEGLUJAN is available for oral use as film-coated tablets containing: 6.48 mg ertugliflozin L-pyroglutamic acid equivalent to 5 mg of ertugliflozin and 128.5 mg sitagliptin phosphate monohydrate equivalent to 100 mg sitagliptin (STEGLUJAN 5/100) 19.43 mg ertugliflozin L-pyroglutamic acid equivalent to 15 mg of ertugliflozin and 128.5 mg sitagliptin phosphate monohydrate equivalent to 100 mg sitagliptin (STEGLUJAN 15/100) Inactive ingredients are microcrystalline cellulose, dibasic calcium phosphate anhydrous, croscarmellose sodium, sodium stearyl fumarate, magnesium stearate, and propyl gallate. The film coating contains: hypromellose, hydroxypropyl cellulose, titanium dioxide, iron oxide red, iron oxide yellow, ferrosoferric oxide/black iron oxide, and carnauba wax. Chemical Structure Chemical Structure

Mechanism of action

12.1 Mechanism of Action STEGLUJAN STEGLUJAN combines two antihyperglycemic agents with complementary mechanisms of action to improve glycemic control in patients with type 2 diabetes mellitus: ertugliflozin, a SGLT2 inhibitor, and sitagliptin, a DPP-4 inhibitor. Ertugliflozin SGLT2 is the predominant transporter responsible for reabsorption of glucose from the glomerular filtrate back into the circulation. Ertugliflozin is an inhibitor of SGLT2. By inhibiting SGLT2, ertugliflozin reduces renal reabsorption of filtered glucose and lowers the renal threshold for glucose, and thereby increases urinary glucose excretion. Sitagliptin Sitagliptin is a DPP-4 inhibitor, which is believed to exert its actions in patients with type 2 diabetes mellitus by slowing the inactivation of incretin hormones. Concentrations of the active intact hormones are increased by sitagliptin, thereby increasing and prolonging the action of these hormones. Incretin hormones, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), are released by the intestine throughout the day, and levels are increased in response to a meal. These hormones are rapidly inactivated by the enzyme, DPP-4. The incretins are part of an endogenous system involved in the physiologic regulation of glucose homeostasis. When blood glucose concentrations are normal or elevated, GLP-1 and GIP increase insulin synthesis and release from pancreatic beta cells by intracellular signaling pathways involving cyclic AMP. GLP-1 also lowers glucagon secretion from pancreatic alpha cells, leading to reduced hepatic glucose production. By increasing and prolonging active incretin levels, sitagliptin increases insulin release and decreases glucagon levels in the circulation in a glucose-dependent manner. Sitagliptin demonstrates selectivity for DPP-4 and does not inhibit DPP-8 or DPP-9 activity in vitro at concentrations approximating those from therapeutic doses.

How supplied

(ertugliflozin and sitagliptin) tablets are available in the strengths listed below: Strength Description How Supplied NDC 5 mg/100 mg tablets beige, almond-shaped, debossed with “554” on one side and plain on the other side. unit-of-use bottles of 30 0006-5367-03 unit-of-use bottles of 90 0006-5367-06 15 mg/100 mg tablets brown, almond-shaped, debossed with “555” on one side and plain on the other side. unit-of-use bottles of 30 0006-5368-03 unit-of-use bottles of 90 0006-5368-06 Store at 20°C-25°C (68°F-77°F), excursions permitted between 15°C-30°C (between 59°F-86°F) [see USP Controlled Room Temperature]. Protect from moisture. Store in a dry place.

Storage

Store at 20°C-25°C (68°F-77°F), excursions permitted between 15°C-30°C (between 59°F-86°F) [see USP Controlled Room Temperature]. Protect from moisture. Store in a dry place.

Patient information

Advise the patient to read the FDA-approved patient labeling ( Medication Guide ). Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis Inform patients that STEGLUJAN 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 dose 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 STEGLUJAN and seek medical attention immediately [see Warnings and Precautions (5.1) ] . Pancreatitis Inform patients that acute pancreatitis has been reported during use of sitagliptin, a component of STEGLUJAN. Inform patients that persistent severe abdominal pain, sometimes radiating to the back, which may or may not be accompanied by vomiting, is the hallmark symptom of acute pancreatitis. Instruct patients to promptly discontinue STEGLUJAN and contact their physician if persistent severe abdominal pain occurs [see Warnings and Precautions (5.2) ] . Lower Limb Amputation Counsel patients about the importance of routine preventative foot care. Instruct patients to monitor for new pain or tenderness, sores or ulcers, or infections involving the leg or foot and to seek medical advice immediately if such signs or symptoms develop [see Warnings and Precautions (5.3) ] . Volume Depletion Inform patients that symptomatic hypotension may occur with STEGLUJAN and advise them to contact their doctor if they experience such symptoms [see Warnings and Precautions (5.5) ] . Inform patients that dehydration may increase the risk for hypotension, and to have adequate fluid intake. Genitourinary Infections, including Urosepsis, Pyelonephritis, Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene), and Genital Mycotic Infections Counsel patients that genitourinary infections may occur when taking STEGLUJAN and may become serious. Educate patients on the symptoms and advise them to seek medical advice if symptoms occur. Specifically, 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, along with a fever above 100.4°F or malaise [see Warnings and Precautions (5.6) ] . Heart Failure Inform patients of the signs and symptoms of heart failure. Instruct patients to contact their health care provider as soon as possible if they experience symptoms of heart failure, including increasing shortness of breath, rapid increase in weight or swelling of the feet [see Warnings and Precautions (5.7) ] . Hypoglycemia with Concomitant Use of Insulin or Insulin Secretagogues Inform patients that the incidence of hypoglycemia may increase when STEGLUJAN is used with insulin or an insulin secretagogue. Educate patients or caregivers on the signs and symptoms of hypoglycemia [see Warnings and Precautions (5.8) ] . Hypersensitivity Reactions Inform patients that allergic reactions have been reported during postmarketing use of sitagliptin, a component of STEGLUJAN. If symptoms of allergic reactions (including rash, hives, and swelling of the face, lips, tongue, and throat that may cause difficulty in breathing or swallowing) occur, instruct patients that they must stop taking STEGLUJAN and seek medical advice promptly [see Warnings and Precautions (5.9) ] . Severe and Disabling Arthralgia Inform patients that severe and disabling joint pain may occur with this class of drugs. The time to onset of symptoms can range from one day to years. Instruct patients to seek medical advice if severe joint pain occurs [see Warnings and Precautions (5.10) ] . Bullous Pemphigoid Inform patients that bullous pemphigoid may occur with the DPP-4 class of drugs. Instruct patients to seek medical advice if blisters or erosions occur [see Warnings and Precautions (5.11) ] . Fetal Toxicity Advise pregnant patients of the potential risk to a fetus with treatment with STEGLUJAN. Instruct patients to immediately inform their healthcare provider if pregnant or planning to become pregnant [see Use in Specific Populations (8.1) ]. Lactation Advise patients that use of STEGLUJAN is not recommended while breastfeeding [see Use in Specific Populations (8.2) ]. Laboratory Tests Due to the mechanism of action of ertugliflozin, inform patients that their urine will test positive for glucose while taking STEGLUJAN. Missed Dose Instruct patients to take STEGLUJAN only as prescribed. If a dose is missed, it should be taken as soon as the patient remembers. Advise patients not to double their next dose [see Dosage and Administration (2.4) ] .

Label text from the FDA structured product label by Merck Sharp & Dohme LLC (revised Jun 3, 2026). Long sections are shortened; the complete label is on DailyMed.

Active ingredients

Ertugliflozin Pidolate in 2 products
Sitagliptin Phosphate in 2 products

Steglujan NDC products (2)

NDC	Strength & form	Labeler	Type
0006-5367	Ertugliflozin Pidolate 5 mg/1; Sitagliptin Phosphate 100 mg/1 Tablet, Film Coated	Merck Sharp & Dohme LLC	NDA
0006-5368	Ertugliflozin Pidolate 15 mg/1; Sitagliptin Phosphate 100 mg/1 Tablet, Film Coated	Merck Sharp & Dohme LLC	NDA

Frequently asked questions

What is Steglujan used for?

What are the side effects of Steglujan?

Who makes Steglujan?

Steglujan is listed by 1 labeler in the FDA NDC directory, including Merck Sharp & Dohme LLC.