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Changes in β-Cell Function and Insulin Sensitivity During Treatment With Dapagliflozin Alone or in Combination With

Curtis Triplitt1,2, Eugenio Cersosimo1,2, Mariam Alatrach1,2

  • 1Division of Diabetes, Department of Medicine, University of Texas Health Science Center, San Antonio, TX.

Diabetes Care
|July 8, 2025
PubMed
Abstract

Insights

Sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide 1 receptor agonists (GLP-1RAs) improve beta-cell function in type 2 diabetes. Combination therapy with SGLT2is and GLP-1RAs showed superior improvements in beta-cell function and insulin sensitivity.

Area of Science:

  • Endocrinology
  • Metabolic Diseases
  • Pharmacology

Background:

  • Type 2 diabetes (T2D) is characterized by impaired beta-cell function (BCF).
  • Sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide 1 receptor agonists (GLP-1RAs) are increasingly used for T2D management.
  • The combined effects of SGLT2is and GLP-1RAs on BCF require further investigation.

Purpose of the Study:

  • To evaluate the impact of SGLT2is and GLP-1RAs, alone or in combination, on BCF in patients with T2D.
  • To test the hypothesis that combination therapy offers superior BCF improvement compared to monotherapy.

Main Methods:

  • Ninety patients with T2D participated in an acute oral glucose tolerance test (OGTT) and therapy over 1 and 4 months.
  • Medications included placebo, dapagliflozin (SGLT2i), exenatide (GLP-1RA), and dapagliflozin/exenatide combination.
  • Calculated indices included corrected Matsuda index (cMI), insulin secretion, and BCF.

Main Results:

  • Acute administration showed increased cMI with dapagliflozin, exenatide, and combination therapy versus placebo.
  • After 1 and 4 months, cMI remained elevated with exenatide and further increased with dapagliflozin and combination therapy.
  • Insulin secretion was higher with exenatide and combination therapy compared to dapagliflozin and placebo.
  • BCF index significantly increased with dapagliflozin, exenatide, and combination therapy acutely and at follow-up, with the combination showing the greatest effect.

Conclusions:

  • Both dapagliflozin and exenatide monotherapy lead to sustained improvements in BCF and insulin sensitivity.
  • Combination therapy with dapagliflozin and exenatide significantly enhanced BCF and insulin sensitivity beyond the effects of either agent alone.

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