Search. Learn. Save

Platform for Pharmaceutical Products for Healthcare Professionals
Search By
☰ Generic Formulas

Generic Formulas X

Ertugliflozin And Sitagliptin

Ertugliflozin and Sitagliptin: A Comprehensive Overview of Fixed-Dose Combination Therapy in Type 2 Diabetes

Introduction

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance and impaired insulin secretion, leading to elevated blood glucose levels. Effective management of T2DM often requires a combination of lifestyle modifications and pharmacological interventions. One such combination is the fixed-dose combination (FDC) of Ertugliflozin and Sitagliptin, marketed under the brand name Steglujan. This therapeutic approach aims to provide enhanced glycemic control through complementary mechanisms of action.

Pharmacology and Mechanism of Action

  • Ertugliflozin: As a sodium-glucose cotransporter 2 (SGLT2) inhibitor, ertugliflozin works by blocking the SGLT2 protein in the kidneys, responsible for reabsorbing glucose back into the bloodstream. By inhibiting this transporter, ertugliflozin promotes the excretion of excess glucose through urine, thereby lowering blood glucose levels.

  • Sitagliptin: A dipeptidyl peptidase-4 (DPP-4) inhibitor, sitagliptin enhances the body's incretin system. It inhibits the DPP-4 enzyme, which is responsible for breaking down incretin hormones like glucagon-like peptide-1 (GLP-1). By prolonging the activity of these hormones, sitagliptin increases insulin release and decreases glucagon secretion in a glucose-dependent manner, leading to improved glycemic control.

When combined, these two agents offer a multifaceted approach to managing T2DM, addressing both insulin resistance and excess glucose production.

Clinical Indications

Steglujan is indicated for:

  • Adults with T2DM inadequately controlled on diet and exercise alone: For patients whose blood glucose levels remain elevated despite optimal lifestyle interventions.

  • Adults already on both ertugliflozin and sitagliptin: To simplify dosing regimens and improve adherence.

  • Adults with T2DM inadequately controlled on metformin and sitagliptin: Offering a combination therapy that includes an SGLT2 inhibitor.

By combining these agents, Steglujan provides a convenient once-daily oral option for patients, potentially improving adherence and overall treatment outcomes.

Efficacy and Clinical Studies

The efficacy of Steglujan has been evaluated in several clinical trials:

  • VERTIS SITA Study: This phase III, randomized, double-blind, multicenter, placebo-controlled 26-week study assessed the efficacy and safety of co-initiation of ertugliflozin and sitagliptin compared with placebo in patients with T2DM inadequately controlled on diet and exercise. The study found that both ertugliflozin/sitagliptin treatments provided significant reductions in HbA1c compared with placebo. At week 26, 35.7% and 31.3% of patients receiving ertugliflozin 5 mg and 15 mg, respectively, achieved HbA1c <7.0%, compared with 8.3% in the placebo group cite turn search.

  • VERTIS SITA2 Study: This study evaluated the addition of ertugliflozin to patients with T2DM inadequately controlled with metformin and sitagliptin. After 26 weeks, both ertugliflozin 5 mg and 15 mg groups showed significant reductions in HbA1c compared with placebo. Additionally, improvements in fasting plasma glucose, body weight, and systolic blood pressure were observed cite turn search.

Safety Profile

While Steglujan is generally well-tolerated, potential side effects may include:

  • Gastrointestinal issues: Such as nausea, vomiting, and diarrhea, particularly during the initiation phase.

  • Genital mycotic infections: Due to increased glucose excretion in the urine, which can promote fungal growth.

  • Urinary tract infections (UTIs): A known risk with SGLT2 inhibitors.

  • Lactic acidosis: A rare but serious complication associated with metformin use, necessitating caution in patients with renal impairment.

Patients should be monitored regularly for renal function, and the medication should be discontinued in cases of acute kidney injury or significant renal decline.

Dosage and Administration

Steglujan is available in various strengths, typically combining 5 mg or 15 mg of ertugliflozin with 100 mg of sitagliptin. The specific dosage should be individualized based on the patient's current regimen, renal function, and treatment goals. It is recommended to take Steglujan with meals to minimize gastrointestinal side effects. Dosing adjustments may be necessary for patients with renal impairment, and the medication is contraindicated in those with severe renal dysfunction.

Benefits Beyond Glycemic Control

In addition to improving glycemic control, Steglujan offers several other benefits:

  • Weight Reduction: By promoting urinary glucose excretion, ertugliflozin leads to calorie loss, contributing to modest weight loss.

  • Blood Pressure Reduction: The osmotic diuretic effect results in mild reductions in systolic and diastolic blood pressure.

Conclusion

Ertugliflozin and Sitagliptin represent a valuable addition to the therapeutic arsenal for managing type 2 diabetes mellitus. Their complementary mechanisms of action, once-daily dosing, and additional benefits such as weight and blood pressure reduction make Steglujan an attractive option for many patients. However, clinicians must remain vigilant regarding potential adverse effects and contraindications to ensure optimal patient outcomes.

References

  1. Verywell Health. "Latest Medication Options for Diabetes." Available at: https://www.verywellhealth.com/new-diabetes-medications-5111874

  2. Mayo Clinic. "Ertugliflozin and Metformin (Oral Route) Side Effects." Available at: https://www.mayoclinic.org/drugs-supplements/ertugliflozin-and-metformin-oral-route/side-effects/drg-20406689

  3. PubMed. "Fixed-dose combination of ertugliflozin and metformin hydrochloride for the treatment of type 2 diabetes." Available at: https://pubmed.ncbi.nlm.nih.gov/30724637

  4. Mayo Clinic. "Ertugliflozin and Metformin (Oral Route) Description."