What is the comparison between Rybelsus (semaglutide), Farxiga (dapagliflozin), and Glipizide?

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Last updated: May 16, 2025View editorial policy

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From the Guidelines

Rybelsus (semaglutide) and Farxiga (dapagliflozin) are preferred over glipizide for the treatment of type 2 diabetes due to their superior efficacy in reducing glucose levels, cardiovascular risk, and kidney disease progression, as well as their lower risk of hypoglycemia, as shown in the most recent study 1.

Medication Comparison

The medications in question, Rybelsus (semaglutide), Farxiga (dapagliflozin), and glipizide, have different mechanisms of action:

  • Rybelsus is a GLP-1 receptor agonist that increases insulin secretion, reduces glucagon, and slows gastric emptying.
  • Farxiga is an SGLT2 inhibitor that causes the kidneys to excrete excess glucose in urine, offering additional benefits for heart and kidney protection.
  • Glipizide is a sulfonylurea that stimulates insulin release from the pancreas.

Key Considerations

When choosing a medication, factors to consider include:

  • A1C levels
  • Cardiovascular risk
  • Kidney function
  • Cost considerations
  • Patient preferences regarding side effect profiles

Side Effects and Risks

Side effects vary among the medications:

  • Rybelsus commonly causes nausea and digestive issues.
  • Farxiga may cause genital yeast infections and urinary tract infections.
  • Glipizide carries a higher risk of hypoglycemia. According to the most recent study 1, GLP-1 receptor agonists, such as Rybelsus, and SGLT2 inhibitors, such as Farxiga, have been shown to have a lower risk of hypoglycemia and superior cardiovascular and kidney benefits compared to sulfonylureas like glipizide. Additionally, a study from 2024 1 found that SGLT2 inhibitors, including Farxiga, reduce the risk of major adverse cardiovascular events and heart failure hospitalization in patients with type 2 diabetes and established cardiovascular disease. Another study from 2022 1 demonstrated that SGLT2 inhibitors, such as Farxiga, have a greater reduction in HbA1c and additional improvement in glucose control when added to other anti-hyperglycemic drugs. Therefore, based on the most recent and highest-quality evidence, Rybelsus and Farxiga are preferred over glipizide for the treatment of type 2 diabetes.

From the Research

Medications for Type 2 Diabetes

  • Rybelsus, Farxiga, and Glipizide are medications used to manage type 2 diabetes, but the provided studies do not directly compare these medications.
  • The studies focus on the role of metformin, dapagliflozin, and other antidiabetic medications in the management of type 2 diabetes 2, 3, 4, 5, 6.

Alternative Medications

  • Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, has been shown to be effective in improving glycemic control, with additional benefits of weight loss and low risk of hypoglycemia 4, 5, 6.
  • Glucagon-like peptide-1 receptor agonists have also demonstrated significant positive effects on glycemia, with added benefits in patients with obesity, renal disease, heart failure, and cardiovascular disease 2, 3.

Combination Therapy

  • Combination therapy with different mechanisms of antidiabetic agents, such as dapagliflozin and metformin, can provide advantages beyond better glycemic improvement, including reduced incidence of hypoglycemia and cardiovascular events 4, 5.
  • The fixed-dose combination of dapagliflozin and metformin has been shown to exert synergistic effects, providing better glycemic control with potential weight loss and reduced incidence of hypoglycemia 5.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Role of metformin in the management of type 2 diabetes: recent advances.

Polish archives of internal medicine, 2023

Research

Should metformin remain the first-line therapy for treatment of type 2 diabetes?

Therapeutic advances in endocrinology and metabolism, 2021

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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