Changes in β-Cell Function and Insulin Sensitivity During Treatment With Dapagliflozin Alone or in Combination With Exenatide in Type 2 Diabetes
Year: 2025
Type: other
Abstract: Objective: To examine the effects of SGLT2i alone or with GLP-1 RA on β-cell function in type 2 diabetes [T2D]. Hypothesis: SGLT-2i, combined with GLP-1 RA, provides superior improvement in β-cell function than either agent alone. Research Design and Methods: 90 patients received 180-min OGTT: (i) after 1 drug dose (ACUTE study): placebo [PCB, n=15]; dapagliflozin [DAPA, n=25]; exenatide [EXE, n=25]; [DAPA/EXE, n=25], and (ii) after 1- and 4-months of therapy. Matsuda index corrected (cMI) for urinary glucose loss, insulin secretion [IS] and β-cell function [BCF] indices were calculated during OGTT. Results: In ACUTE study, cMI in DAPA (2.29±0.33), EXE (2.03±0.12) and DAPA+EXE (2.36±0.14) were higher (p<0.05) than PCB (1.63±0.36). After 1- and 4-months, cMI remained similarly elevated in EXE and increased further (p<0.001) in DAPA and DAPA+EXE. In ACUTE study, IS in DAPA was similar to PCB but higher (p<0.001 vs. both) in EXE and DAPA/EXE. After 1- and 4-months in EXE and in DAPA+EXE, IS remained higher (p<0.01 vs. both) than DAPA. BCF index in ACUTE study was 0.40±0.04 in PCB, 62% higher (p<0.05) in DAPA (0.65±0.10), 3-fold higher in EXE (1.17±0.22) and 4-fold higher in DAPA+EXE (1.69±0.12) (all p<0.001 vs. PCB). At 1-month and 4-months BCF rose further in DAPA and EXE but did not increase further in DAPA+EXE. Conclusion: Dapagliflozin and exenatide monotherapy cause sustained improvements in β-cell function and insulin sensitivity. Combination therapy with dapagliflozin plus exenatide markedly augmented both b-cell function and insulin sensitivity above that with either agent alone.
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4412106972