STEGLATRO™

(ertugliflozin) 5 mg, 15 mg tablets

Efficacy Profile

STEGLATRO added to metformin and sitagliptin

Learn about the results of the placebo-controlled, randomized study VERTIS SITA2:

  • A1C (primary end point)
  • Study design
  • FPG (secondary end point)
  • BW (secondary end point)
  • (STEGLATRO is not indicated for weight loss.)
  • SBP (secondary end point)
  • (STEGLATRO is not indicated for the treatment of hypertension.)

A1C

As an adjunct to diet and exercise for appropriate adults with type 2 diabetes:

Powerful A1C reductions with STEGLATRO added to metformin and sitagliptin1

Primary end point: A1C change from baseline at week 26a,b

Vertis Sita2: A1C Data for STEGLATRO™ (ertugliflozin)

(a) N includes all randomized and treated patients with a baseline measurement of the outcome variable. At week 26, the primary A1C end point was missing for 10%, 11%, and 7% of patients, and during the trial, rescue medication was initiated by 16%, 1%, and 2% of patients randomized to placebo, STEGLATRO 5 mg, and STEGLATRO 15 mg, respectively. Missing week 26 measurements were imputed using multiple imputation with a mean equal to the baseline value of the patient. Results include measurements collected after initiation of rescue medication. For those patients who did not receive rescue medication and had values measured at 26 weeks, the mean changes from baseline for A1C were –0.2%, –0.8%, and –0.9% for placebo, STEGLATRO 5 mg, and STEGLATRO 15 mg, respectively.

(b) Intent-to-treat analysis using ANCOVA adjusted for baseline value, prior antihyperglycemic medication, and baseline eGFR.

ANCOVA, analysis of covariance; BL, baseline; eGFR, estimated glomerular filtration rate; LS, least squares.

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Study design

A total of 463 adults with type 2 diabetes inadequately controlled (A1C between 7% and 10.5%) on metformin (≥1500 mg/day for ≥8 weeks) and sitagliptin 100 mg once daily participated in a randomized, double-blind, multicenter, 26-week, placebo-controlled study to evaluate the efficacy and safety of STEGLATRO. Patients entered a 2-week, single-blind, placebo run-in period and were randomized to placebo, STEGLATRO 5 mg, or STEGLATRO 15 mg. The primary efficacy end point was the change from baseline in A1C at week 26.1

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FPG

As an adjunct to diet and exercise for appropriate adults with type 2 diabetes:

Significant FPG reductions with STEGLATRO added to metformin and sitagliptin1

Secondary end point: Change in FPG from baseline at week 26c

Vertis Sita2: FPG Data for STEGLATRO™ (ertugliflozin)

(c) Intent-to-treat analysis using ANCOVA adjusted for baseline value, prior antihyperglycemic medication, and baseline eGFR.

ANCOVA, analysis of covariance; BL, baseline; eGFR, estimated glomerular filtration rate; FPG, fasting plasma glucose; LS, least squares.

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Body weight

As an adjunct to diet and exercise for appropriate adults with type 2 diabetes:

Significant reductions in body weight with STEGLATRO added to metformin and sitagliptin1,2

Secondary end point: Change in body weight from baseline at week 26

Vertis Sita2: Body Weight Data for STEGLATRO™ (ertugliflozin)

STEGLATRO is not indicated for weight loss.

BL, baseline; LS, least squares.

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SBP

As an adjunct to diet and exercise for appropriate adults with type 2 diabetes:

Significant reductions in SBP with STEGLATRO added to metformin and sitagliptin1,2

Secondary end point: Change in systolic blood pressure from baseline at week 26

Vertis Sita2: SBP Data for STEGLATRO™ (ertugliflozin)

STEGLATRO is not indicated for the treatment of hypertension.

BL, baseline; LS, least squares; SBP, systolic blood pressure.

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Indication

STEGLATRO is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. STEGLATRO is not recommended in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.

Selected Safety Information

Contraindications: STEGLATRO is contraindicated in patients with severe renal impairment, end-stage renal disease, or on dialysis, and/or a history of a serious hypersensitivity reaction to ertugliflozin.

Hypotension: STEGLATRO causes intravascular volume contraction. Symptomatic hypotension may occur after initiating STEGLATRO, particularly in patients with impaired renal function (estimated glomerular filtration rate [eGFR] less than 60 mL/min/1.73 m2), elderly patients (≥65 years), patients with low systolic blood pressure, or patients on diuretics. Before initiating STEGLATRO, volume status should be assessed and corrected if indicated. Monitor for signs and symptoms after initiating therapy.

Ketoacidosis: Ketoacidosis, a serious life-threatening condition requiring urgent hospitalization, has been reported in patients with type 1 and type 2 diabetes receiving sodium glucose co-transporter 2 (SGLT2) inhibitors, including STEGLATRO. Some cases were fatal. Assess patients with signs and symptoms of metabolic acidosis for ketoacidosis, regardless of blood glucose level. If ketoacidosis is suspected, STEGLATRO should be discontinued, patients should be evaluated, and prompt treatment should be instituted. Before initiating STEGLATRO, consider risk factors for ketoacidosis, including pancreatic insulin deficiency from any cause, caloric restriction, and alcohol abuse. In patients treated with STEGLATRO, consider monitoring for ketoacidosis and temporarily discontinuing STEGLATRO in clinical situations known to predispose to ketoacidosis (eg, prolonged fasting due to acute illness or surgery).

Acute Kidney Injury and Impairment in Renal Function: STEGLATRO causes intravascular volume contraction and can cause renal impairment. There have been postmarketing reports of acute kidney injury, some requiring hospitalization and dialysis, in patients receiving SGLT2 inhibitors. Before initiating STEGLATRO, consider factors that may predispose patients to acute kidney injury. Consider temporarily discontinuing STEGLATRO in any setting of reduced oral intake or fluid losses; monitor patients for signs and symptoms of acute kidney injury. If acute kidney injury occurs, discontinue STEGLATRO promptly and institute treatment.

STEGLATRO increases serum creatinine and decreases eGFR. Patients with moderate renal impairment (eGFR 30 to less than 60 mL/min/1.73 m2) may be more susceptible to these changes. Renal function abnormalities can occur after initiating STEGLATRO. Renal function should be evaluated prior to initiating STEGLATRO and periodically thereafter. Use of STEGLATRO is not recommended when eGFR is persistently between 30 and less than 60 mL/min/1.73 m2 and is contraindicated in patients with an eGFR less than 30 mL/min/1.73 m2.

Urosepsis and Pyelonephritis: There have been postmarketing reports of serious urinary tract infections, including urosepsis and pyelonephritis, requiring hospitalization in patients receiving SGLT2 inhibitors. Cases of pyelonephritis also have been reported in patients treated with STEGLATRO in clinical trials. Treatment with SGLT2 inhibitors increases the risk for urinary tract infections. Evaluate patients for signs and symptoms of urinary tract infections and treat promptly, if indicated.

Lower Limb Amputations: An increased risk for lower limb amputation has been observed in clinical studies with another SGLT2 inhibitor. Across seven Phase 3 clinical trials with STEGLATRO, nontraumatic lower limb amputations were reported in 1 (0.1%) patient in the comparator group, 3 (0.2%) patients in the STEGLATRO 5-mg group, and 8 (0.5%) patients in the STEGLATRO 15-mg group. A causal association between STEGLATRO and lower limb amputation has not been definitively established. Before initiating STEGLATRO, consider factors that may predispose patients to the need for amputations. Monitor patients and discontinue STEGLATRO if complications occur. Counsel patients about the importance of routine preventative foot care.

Hypoglycemia With Concomitant Use With Insulin and Insulin Secretagogues: Insulin and insulin secretagogues (eg, sulfonylurea) are known to cause hypoglycemia. STEGLATRO may increase the risk of hypoglycemia when used in combination with insulin and/or an insulin secretagogue. Therefore, a lower dose of insulin or insulin secretagogue may be required to minimize the risk of hypoglycemia when used in combination with STEGLATRO.

Necrotizing Fasciitis of the Perineum (Fournier's Gangrene): A rare but serious and life-threatening necrotizing infection requiring urgent surgical intervention has been reported in post-marketing surveillance in females and males with diabetes mellitus receiving SGLT2 inhibitors. Serious outcomes have included hospitalization, multiple surgeries, and death. Patients treated with STEGLATRO presenting with pain or tenderness, erythema, or swelling in the genital or perineal area, along with fever or malaise, should be assessed for necrotizing fasciitis. If suspected, start treatment immediately with broad-spectrum antibiotics and, if necessary, surgical debridement. Discontinue STEGLATRO, closely monitor blood glucose levels, and provide appropriate alternative therapy for glycemic control.

Genital Mycotic Infections: STEGLATRO increases the risk of genital mycotic infections. Patients who have a history of genital mycotic infections or who are uncircumcised are more likely to develop genital mycotic infections. Monitor and treat appropriately.

Increases in Low-Density Lipoprotein Cholesterol (LDL-C): Dose-related increases in LDL-C can occur with STEGLATRO. Monitor and treat as appropriate.

Macrovascular Outcomes: There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with STEGLATRO.

The most common adverse reactions associated with STEGLATRO (≥5%) were female genital mycotic infections.

Before prescribing STEGLATRO™ (ertugliflozin), please read the accompanying Prescribing Information. The Medication Guide also is available.

References

1. 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(3):530–540.

2. Data available on request from Merck Professional Services-DAP, WP1-27, PO Box 4, West Point, PA 19486-0004. Please specify information package US-STE-00104.

US-STE-0029704/19