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 (2024)

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Volume 47, Issue 7

July 2024

Original Article| April 23 2024

Giuseppe Daniele

;

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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Stefano Del Prato

Stefano Del Prato

4Interdisciplinary Research Center for Health Science, Sant’Anna School of Advanced Studies, 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:

38652656

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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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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 (2024)

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