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Volume 47, Issue 7
July 2024
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Original Article| April 23 2024
Giuseppe Daniele
;
1Section of Metabolic Diseases and Diabetes, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
Corresponding author: Giuseppe Daniele, giuseppe.daniele@unipi.it
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Andrea Tura
;
Andrea Tura
2Metabolic Unit, Consiglio Nazionale delle Ricerche Institute of Neuroscience, Padova, Italy
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Alex Brocchi;
Alex Brocchi
1Section of Metabolic Diseases and Diabetes, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
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Alessandro Saba;
Alessandro Saba
3Department of Surgical, Medical, Molecular, and Critical Care Pathology, University of Pisa, Pisa, Italy
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Beatrice Campi;
Beatrice Campi
3Department of Surgical, Medical, Molecular, and Critical Care Pathology, University of Pisa, Pisa, Italy
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Veronica Sancho-Bornez;
Veronica Sancho-Bornez
1Section of Metabolic Diseases and Diabetes, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
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Angela Dardano
;
Angela Dardano
1Section of Metabolic Diseases and Diabetes, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
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Corresponding author: Giuseppe Daniele, giuseppe.daniele@unipi.it
Diabetes Care 2024;47(7):1131–1139
Article history
Received:
November 01 2023
Accepted:
April 02 2024
PubMed:
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Citation
Giuseppe Daniele, Andrea Tura, Alex Brocchi, Alessandro Saba, Beatrice Campi, Veronica Sancho-Bornez, Angela Dardano, Stefano Del Prato; β-Cell Function, Incretin Effect, and Glucose Kinetics in Response to a Mixed Meal in Patients With Type 2 Diabetes Treated With Dapagliflozin Plus Saxagliptin. Diabetes Care 20 June 2024; 47 (7): 1131–1139. https://doi.org/10.2337/dc23-2051
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OBJECTIVE
To explore the complementary effects of a combination of dipeptidyl peptidase 4 and sodium–glucose cotransporter 2 inhibitors added to metformin on hormonal and metabolic responses to meal ingestion.
RESEARCH DESIGN AND METHODS
Forty-five patients (age 58 ± 8 years; HbA1c 58 ± 6 mmol/mol; BMI 30.7 ± 3.2 kg/m2) with type 2 diabetes uncontrolled with metformin were evaluated at baseline and 3 and 28 days after 5 mg saxagliptin (SAXA), 10 mg dapagliflozin (DAPA), or 5 mg saxagliptin plus 10 mg dapagliflozin (SAXA+DAPA) using a mixed-meal tolerance test (MMTT) spiked with dual-tracer glucose to assess glucose metabolism, insulin secretion, and sensitivity.
RESULTS
At day 3, fasting and mean MMTT glucose levels were lower with SAXA+DAPA (−31.1 ± 1.6 and −91.5 ± 12.4 mg/dL) than with SAXA (−7.1 ± 2.1 and −53 ± 10.5 mg/dL) or DAPA (−17.0 ± 1.1 and −42.6 ± 10.0 mg/dL, respectively; P < 0.001). Insulin secretion rate (SAXA+DAPA +75%; SAXA +11%; DAPA +3%) and insulin sensitivity (+2.2 ± 1.7, +0.4 ± 0.7, and +0.4 ± 0.4 mg ⋅ kg−1⋅ min−1, respectively) improved with SAXA+DAPA (P < 0.007). Mean glucagon-like peptide 1 (GLP-1) was higher with SAXA+DAPA than with SAXA or DAPA. Fasting glucagon increased with DAPA and SAXA+DAPA but not with SAXA. Fasting endogenous glucose production (EGP) increased with SAXA+DAPA and DAPA. During MMTT, EGP suppression was greater (48%) with SAXA+DAPA (vs. SAXA 44%; P = 0.02 or DAPA 34%; P = 0.2). Metabolic clearance rate of glucose (MCRglu) increased more with SAXA+DAPA. At week 4, insulin secretion rate, β-cell glucose sensitivity, and insulin sensitivity had further increased in the SAXA+DAPA group (P = 0.02), with no additional changes in GLP-1, glucagon, fasting or MMTT EGP, or MCRglu.
CONCLUSIONS
SAXA+DAPA provided superior glycemic control compared with DAPA or SAXA, with improved β-cell function, insulin sensitivity, GLP-1 availability, and glucose clearance.
Clinical trial reg. nos. NCT03714594, clinicaltrials.gov, and EudraCT2016-005140-41, https://eudract.ema.europa.eu
This article contains supplementary material online at https://doi.org/10.2337/figshare.25541839.
© 2024 by the American Diabetes Association
2024
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at https://www.diabetesjournals.org/journals/pages/license.
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