Acute and long-term effects of saxagliptin on post-prandial glycemic response in obese patients with impaired glucose tolerance.


Journal

Nutrition, metabolism, and cardiovascular diseases : NMCD
ISSN: 1590-3729
Titre abrégé: Nutr Metab Cardiovasc Dis
Pays: Netherlands
ID NLM: 9111474

Informations de publication

Date de publication:
09 04 2021
Historique:
received: 25 07 2020
revised: 25 11 2020
accepted: 22 12 2020
pubmed: 24 2 2021
medline: 7 4 2021
entrez: 23 2 2021
Statut: ppublish

Résumé

Dipeptidyl-peptidase inhibitors might be useful in type 2 diabetes prevention. ACCES (ACute and Chronic Effects of Saxagliptin) was a randomized, placebo-controlled, double-blind, controlled phase 2, pilot study aiming to examine in obese patients with impaired glucose tolerance (IGT) the acute effects and the effects after 12 weeks of treatment by saxagliptin on glucose levels at fasting and postprandially after a standard breakfast, and on glucose tolerance. We included 24 obese patients with IGT. Patients were randomized to receive saxagliptin 5 mg or placebo in the morning. The treatment was taken on Visit 1 before breakfast, then continued for 12 weeks. Biochemical measurements were performed before, one, two and three hours after a standard breakfast including 75 g of carbohydrates, during Visit 1 and Visit 2 (12 weeks). Glucose variability (GV) was evaluated at Visit 1 from 24-h continuous glucose monitoring including the breakfast. A second OGTT was performed at Visit 3 (3-5 days after Visit 2). Compared with placebo-treated patients, saxagliptin-treated patients had lower 1 h and 2 h post-meal plasma glucose levels at Visit 1 and similar changes at Visit 2 (p < 0.01 to p < 0.004), with lower GV indexes after breakfast at Visit 1. At Visit 3, all patients but one in saxagliptin group and only 4 patients in placebo group turned to normal glucose tolerance. Lower glucose response to breakfast at Visit 1 was predictive of recovery of glucose tolerance. Saxagliptin has metabolically beneficial effects in glucose-intolerant obese patients by significantly lowering postprandial blood glucose levels. NCT01521312: https://clinicaltrials.gov/ct2/show/NCT01521312.

Sections du résumé

BACKGROUND AND AIMS
Dipeptidyl-peptidase inhibitors might be useful in type 2 diabetes prevention. ACCES (ACute and Chronic Effects of Saxagliptin) was a randomized, placebo-controlled, double-blind, controlled phase 2, pilot study aiming to examine in obese patients with impaired glucose tolerance (IGT) the acute effects and the effects after 12 weeks of treatment by saxagliptin on glucose levels at fasting and postprandially after a standard breakfast, and on glucose tolerance.
METHODS AND RESULTS
We included 24 obese patients with IGT. Patients were randomized to receive saxagliptin 5 mg or placebo in the morning. The treatment was taken on Visit 1 before breakfast, then continued for 12 weeks. Biochemical measurements were performed before, one, two and three hours after a standard breakfast including 75 g of carbohydrates, during Visit 1 and Visit 2 (12 weeks). Glucose variability (GV) was evaluated at Visit 1 from 24-h continuous glucose monitoring including the breakfast. A second OGTT was performed at Visit 3 (3-5 days after Visit 2). Compared with placebo-treated patients, saxagliptin-treated patients had lower 1 h and 2 h post-meal plasma glucose levels at Visit 1 and similar changes at Visit 2 (p < 0.01 to p < 0.004), with lower GV indexes after breakfast at Visit 1. At Visit 3, all patients but one in saxagliptin group and only 4 patients in placebo group turned to normal glucose tolerance. Lower glucose response to breakfast at Visit 1 was predictive of recovery of glucose tolerance.
CONCLUSION
Saxagliptin has metabolically beneficial effects in glucose-intolerant obese patients by significantly lowering postprandial blood glucose levels.
CLINICAL TRIAL REGISTRATION NUMBER
NCT01521312: https://clinicaltrials.gov/ct2/show/NCT01521312.

Identifiants

pubmed: 33618922
pii: S0939-4753(20)30551-2
doi: 10.1016/j.numecd.2020.12.025
pii:
doi:

Substances chimiques

Biomarkers 0
Blood Glucose 0
Dipeptides 0
Dipeptidyl-Peptidase IV Inhibitors 0
saxagliptin 9GB927LAJW
Adamantane PJY633525U

Banques de données

ClinicalTrials.gov
['NCT01521312']

Types de publication

Clinical Trial, Phase II Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1257-1266

Informations de copyright

Copyright © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Auteurs

Amel Rezki (A)

Department of Endocrinology, Diabetology, Nutrition, Jean Verdier Hospital, AP-HP, CRNH-IdF, CINFO, Paris Nord University, Sorbonne Paris Cité, Bondy, France; Sorbonne Paris Cité, UMR U1153 Inserm/U1125 Inra/Cnam/Université Paris 13, Bobigny, France.

Marinos Fysekidis (M)

Department of Endocrinology, Diabetology, Nutrition, Jean Verdier Hospital, AP-HP, CRNH-IdF, CINFO, Paris Nord University, Sorbonne Paris Cité, Bondy, France; Sorbonne Paris Cité, UMR U1153 Inserm/U1125 Inra/Cnam/Université Paris 13, Bobigny, France.

Sabrina Chiheb (S)

Department of Endocrinology, Diabetology, Nutrition, Jean Verdier Hospital, AP-HP, CRNH-IdF, CINFO, Paris Nord University, Sorbonne Paris Cité, Bondy, France.

Eric Vicaut (E)

Clinical Research Unit, Lariboisière-St Louis, Fernand Widal Hospital, APHP, Paris, France.

Emmanuel Cosson (E)

Department of Endocrinology, Diabetology, Nutrition, Jean Verdier Hospital, AP-HP, CRNH-IdF, CINFO, Paris Nord University, Sorbonne Paris Cité, Bondy, France; Sorbonne Paris Cité, UMR U1153 Inserm/U1125 Inra/Cnam/Université Paris 13, Bobigny, France.

Paul Valensi (P)

Department of Endocrinology, Diabetology, Nutrition, Jean Verdier Hospital, AP-HP, CRNH-IdF, CINFO, Paris Nord University, Sorbonne Paris Cité, Bondy, France. Electronic address: paul.valensi@aphp.fr.

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Classifications MeSH