SEGLUROMET

Boxed Warning 8/2026 Dosage and Administration Recommendations Regarding Missed Dose ( 2.5 ) 8/2026 Warnings and Precautions Lactic Acidosis ( 5.1 ) Genitourinary Infections, including Urosepsis, Pyelonephritis, Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene), and Genital Mycotic Infections ( 5.5 ) 8/2026 8/2026

1 INDICATIONS AND USAGE SEGLUROMET ® is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. SEGLUROMET is a combination of ertugliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, and metformin, a biguanide, indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. ( 1 ) Limitations of Use: Not recommended for use to improve glycemic control in patients with type 1 diabetes mellitus. ( 1 ) Limitations of Use Not recommended for use to improve glycemic control in patients with type 1 diabetes mellitus [see Warnings and Precautions (5.2) ].

2 DOSAGE AND ADMINISTRATION Assess renal function prior to initiation and as clinically indicated. ( 2.1 ) Correct volume depletion before initiation. ( 2.1 ) Individualize the starting dosage based on the patient's current regimen. ( 2.2 ) Maximum recommended dosage is 7.5 mg ertugliflozin/1,000 mg metformin orally twice daily. ( 2.2 ) Take orally twice daily with meals, with gradual dose escalation. ( 2.2 ) Do not use in patients with an estimated glomerular filtration rate (eGFR) below 30 mL/minute/1.73 m 2 . Use is not recommended in patients with an eGFR less than 45 mL/min/1.73 m 2 . ( 2.2 ) Use 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. ( 2.2 ) SEGLUROMET may need to be discontinued at time of, or prior to, iodinated contrast imaging procedures. ( 2.3 ) Withhold SEGLUROMET for at least 4 days, if possible, prior to surgery or procedures associated with prolonged fasting. ( 2.4 ) 2.1 Prior to Initiation of SEGLUROMET Assess renal function before initiating SEGLUROMET and as clinically indicated [see Warnings and Precautions (5.1 , 5.4) ] . Assess volume status. In patients with volume depletion, correct this condition before initiating SEGLUROMET [see Warnings and Precautions (5.4) and Use in Specific Populations (8.5 , 8.6) ]. 2.2 Recommended Dosage Individualize the starting dosage of SEGLUROMET, ertugliflozin and metformin hydrochloride (HCI), based on the patient’s current regimen, while not exceeding the maximum recommended oral daily dosage of 15 mg ertugliflozin and 2,000 mg metformin HCl: In patients on metformin HCI, switch to SEGLUROMET tablets containing 2.5 mg ertugliflozin, with a similar total oral daily dosage of metformin HCl. In patients on ertugliflozin, switch to SEGLUROMET tablets containing 500 mg metformin HCl, with a similar total oral daily dosage of ertugliflozin. In patients already treated with ertugliflozin and metformin HCl, switch to SEGLUROMET tablets containing the same total oral daily dosage of ertugliflozin and a similar daily dosage of metformin HCI. Take SEGLUROMET orally twice daily with meals, with gradual dosage escalation for those initiating metformin HCl to reduce the gastrointestinal side effects due to metformin [see Adverse Reactions (6.1) ]. Dosing may be adjusted based on effectiveness and tolerability. Use of SEGLUROMET is not recommended in patients with an estimated glomerular filtration rate (eGFR) less than 45 mL/min/1.73 m 2 . Use of SEGLUROMET 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 Discontinuation for Iodinated Contrast Imaging Procedures Discontinue SEGLUROMET at the time of, or prior to, an iodinated contrast imaging procedure in patients with an eGFR less than 60 mL/min/1.73 m 2 ; in patients with a history of liver disease, alcoholism or heart failure; or in patients who will be administered intra-arterial iodinated contrast. Re-evaluate eGFR 48 hours after the imaging procedure; restart SEGLUROMET if renal function is stable [see Warnings and Precautions (5.1) ] . 2.4 Temporary Interruption for Surgery Withhold SEGLUROMET for at least 4 days, if possible, prior to surgery or procedures associated with prolonged fasting. Resume SEGLUROMET when the patient is clinically stable and has resumed oral intake [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.2) ]. 2.5 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.

3 DOSAGE FORMS AND STRENGTHS Tablets: ertugliflozin 2.5 mg and metformin HCl 500 mg, pink, oval, debossed with "2.5/500" on one side and plain on the other side. Tablets: ertugliflozin 2.5 mg and metformin HCl 1,000 mg, pink, oval, debossed with "2.5/1000" on one side and plain on the other side. Tablets: ertugliflozin 7.5 mg and metformin HCl 500 mg, red, oval, debossed with "7.5/500" on one side and plain on the other side. Tablets: ertugliflozin 7.5 mg and metformin HCl 1,000 mg, red, oval, debossed with "7.5/1000" on one side and plain on the other side. Tablets: Ertugliflozin 2.5 mg and metformin hydrochloride 500 mg ( 3 ) Ertugliflozin 2.5 mg and metformin hydrochloride 1,000 mg ( 3 ) Ertugliflozin 7.5 mg and metformin hydrochloride 500 mg ( 3 ) Ertugliflozin 7.5 mg and metformin hydrochloride 1,000 mg ( 3 )

4 CONTRAINDICATIONS SEGLUROMET is contraindicated in patients with: Hypersensitivity to ertugliflozin, metformin, or any excipient in SEGLUROMET. Reactions such as angioedema or anaphylaxis have occurred [see Adverse Reactions (6.2) ]. Severe renal impairment (eGFR less than 30 mL/min/1.73 m 2 ), end stage-renal disease (ESRD), or on dialysis [see Use in Specific Populations (8.6) ] . Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. Severe renal impairment (eGFR less than 30 mL/min/1.73 m 2 ), end stage-renal disease, or patients on dialysis. ( 4 ) Metabolic acidosis, including diabetic ketoacidosis. ( 4 ) Hypersensitivity to ertugliflozin, metformin or any excipient. ( 4 )

6 ADVERSE REACTIONS The following important adverse reactions are described elsewhere in the labeling: Lactic Acidosis [see Boxed Warning and Warnings and Precautions (5.1) ] Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis [see Warnings and Precautions (5.2) ] Lower Limb Amputation [see Warnings and Precautions (5.3) ] Volume Depletion [see Warnings and Precautions (5.4) ] Genitourinary Infections, including Urosepsis, Pyelonephritis, Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene), and Genital Mycotic Infections [see Warnings and Precautions (5.5) ] Hypoglycemia with Concomitant Use with Insulin or Insulin Secretagogues [see Warnings and Precautions (5.6) ] Vitamin B 12 Deficiency [see Warnings and Precautions (5.7) ] Most common adverse reactions associated with ertugliflozin (incidence ≥5%) were female genital mycotic infections. ( 6.1 ) Most common adverse reactions associated with metformin (incidence ≥5%) were diarrhea, nausea, vomiting, flatulence, abdominal discomfort, indigestion, asthenia, and headache. ( 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 Metformin Hydrochloride The incidence and type of adverse reactions in the two 26-week, placebo-controlled trials of ertugliflozin 5 mg and 15 mg added to metformin HCl, representing a majority of data from the three 26-week, placebo-controlled trials, were similar to the adverse reactions described 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=24 …

7 DRUG INTERACTIONS Table 3: Clinically Significant Drug Interactions with SEGLUROMET Carbonic Anhydrase Inhibitors Clinical Impact: The risk of lactic acidosis may increase due to concomitant use of Topiramate or other carbonic anhydrase inhibitors (e.g., zonisamide, acetazolamide or dichlorphenamide) with metformin. These drugs frequently cause a decrease in serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Intervention: more frequent monitoring of these patients. Drugs that Reduce Metformin Clearance Clinical Impact: The risk of lactic acidosis may increase due to concomitant use of drugs that interfere with common renal tubular transport systems involved in the renal elimination of metformin (e.g., organic cationic transporter-2 [OCT2] / multidrug and toxin extrusion [MATE] inhibitors such as ranolazine, vandetanib, dolutegravir, and cimetidine) which increase systemic exposure to metformin Intervention Consider the benefits and risks of concomitant use. Alcohol Clinical Impact: Potentiate the effect of metformin on lactate metabolism. Intervention: Warn patients against excessive alcohol intake while receiving SEGLUROMET. Insulin or Insulin Secretagogues Clinical Impact: The risk of hypoglycemia is increased when ertugliflozin 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 SEGLUROMET. Drugs that Affect Glycemic Control Clinical Impact: Certain drugs tend to produce hyperglycemia and may lead to loss of glycemic control. These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, and isoniazid. Intervention: When a patient is receiving SEGLUROMET along with such drugs, the patient should be closely observed to maintain adequate glycemic control. Lithium Clinical Impact: Concomitant use of an SGLT2 inhibitor with lithium may decrease serum lithium concentrations. Intervention: Monitor serum lithium concentration more frequently during SEGLUROMET 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 SEGLUROMET. 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. Carbonic Anhydrase Inhibitors: May increase risk of lactic acidosis. Consider more frequent monitoring. ( 7 ) Drugs that Reduce Metformin Clearance: May increase risk of lactic acidosis. Consider benefits and risks of concomitant use. ( 7 ) See full prescribing information for additional drug interactions and information on interference of SEGLUROMET with laboratory tests. ( 7 )

8 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 ) Females and Males of Reproductive Potential: Advise premenopausal females of the potential for an unintended pregnancy. ( 8.3 ) 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 ) Hepatic impairment : Avoid use in patients with hepatic impairment. ( 8.7 ) 8.1 Pregnancy Risk Summary Based on animal data showing adverse renal effects, from ertugliflozin, SEGLUROMET is not recommended during the second and third trimesters of pregnancy. Published studies with metformin use during pregnancy have not reported a clear association with metformin and major birth defect or miscarriage risk (see Data ) . The limited available data with SEGLUROMET in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or miscarriage. 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 ) . 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 Human Data Published data from postmarketing studies have not reported a clear association with metformin and major birth defects, miscarriage, or adverse maternal or fetal outcomes when metformin was used during pregnancy. However, these studies cannot definitely establish the absence of any metformin-associated risk because of methodological limitations, including small sample size and inconsistent comparator groups. 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 AU …

12.1 Mechanism of Action SEGLUROMET SEGLUROMET 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 metformin hydrochloride, a member of the biguanide class. 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. Metformin HCl Metformin is an antihyperglycemic agent which improves glucose tolerance in patients with type 2 diabetes mellitus, lowering both basal and postprandial plasma glucose. Its pharmacologic mechanisms of action are different from other classes of oral antihyperglycemic agents. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. Metformin does not produce hypoglycemia in either patients with type 2 diabetes mellitus or normal subjects (except in special circumstances) [see Warnings and Precautions (5.6) ] and does not cause hyperinsulinemia. With metformin therapy, insulin secretion remains unchanged while fasting insulin levels and day-long plasma insulin response may actually decrease.

11 DESCRIPTION SEGLUROMET (ertugliflozin and metformin hydrochloride) tablet for oral use contains ertugliflozin L-pyroglutamic acid, a SGLT2 inhibitor, and metformin HCl, a member of the biguanide class. 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. Chemical Structure Metformin HCl Metformin hydrochloride ( N , N -dimethylimidodicarbonimidic diamide hydrochloride) is not chemically or pharmacologically related to any other classes of oral antihyperglycemic agents. The structural formula is as shown: Metformin HCl is a white to off-white crystalline compound with a molecular formula of C 4 H 11 N 5 ∙HCl and a molecular weight of 165.63. Metformin hydrochloride is freely soluble in water and is practically insoluble in acetone, ether and chloroform. The pK a of metformin is 12.4. The pH of a 1% aqueous solution of metformin hydrochloride is 6.68. SEGLUROMET is available as film-coated tablets containing: 3.24 mg ertugliflozin L-pyroglutamic acid equivalent to 2.5 mg of ertugliflozin and 500 mg metformin HCl (SEGLUROMET 2.5/500) 3.24 mg ertugliflozin L-pyroglutamic acid equivalent to 2.5 mg of ertugliflozin and 1,000 mg metformin HCl (SEGLUROMET 2.5/1000) 9.71 mg ertugliflozin L-pyroglutamic acid equivalent to 7.5 mg of ertugliflozin and 500 mg metformin HCl (SEGLUROMET 7.5/500) 9.71 mg ertugliflozin L-pyroglutamic acid equivalent to 7.5 mg of ertugliflozin and 1,000 mg metformin HCl (SEGLUROMET 7.5/1000) Inactive ingredients are povidone, microcrystalline cellulose, crospovidone, sodium lauryl sulfate, and magnesium stearate. The film coating contains: hypromellose, hydroxypropyl cellulose, titanium dioxide, iron oxide red, and carnauba wax. Chemical Structure

10 OVERDOSAGE SEGLUROMET In the event of an overdose with SEGLUROMET, 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. Metformin HCl Overdose of metformin hydrochloride has occurred, including ingestion of amounts greater than 50 g (25 times the maximum recommended daily dose). Hypoglycemia was reported in approximately 10% of cases, but no causal association with metformin hydrochloride has been established. Lactic acidosis has been reported in approximately 32% of metformin overdose cases [see Warnings and Precautions (5.1) ] . Metformin is dialyzable with a clearance of up to 170 mL/min under good hemodynamic conditions. Therefore, hemodialysis may be useful for removal of accumulated drug from patients in whom metformin overdosage is suspected.

16 HOW SUPPLIED/STORAGE AND HANDLING SEGLUROMET (ertugliflozin and metformin hydrochloride) tablets are available as follows: Strength Description How Supplied NDC ertugliflozin 2.5 mg and metformin hydrochloride 500 mg tablets pink, oval, debossed with “2.5/500” on one side and plain on the other side unit-of-use bottles of 60 0006-5369-03 unit-of-use bottles of 180 0006-5369-06 ertugliflozin 2.5 mg and metformin hydrochloride 1,000 mg tablets pink, oval, debossed with “2.5/1000” on one side and plain on the other side unit-of-use bottles of 60 0006-5373-03 unit-of-use bottles of 180 0006-5373-06 ertugliflozin 7.5 mg and metformin hydrochloride 500 mg tablets red, oval, debossed with “7.5/500” on one side and plain on the other side unit-of-use bottles of 60 0006-5370-03 unit-of-use bottles of 180 0006-5370-06 ertugliflozin 7.5 mg and metformin hydrochloride 1,000 mg tablets red, oval, debossed with “7.5/1000” on one side and plain on the other side unit-of-use bottles of 60 0006-5374-03 unit-of-use bottles of 180 0006-5374-06 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.