Cargando…

Up-Titration Strategy After DPP-4 Inhibitor-Based Oral Therapy for Type 2 Diabetes: A Randomized Controlled Trial Shifting to a Single-Dose GLP-1 Enhancer Versus Adding a Variable Basal Insulin Algorithm

INTRODUCTION: It is unclear whether adding basal insulin or enhancing incretin signaling with a glucagon-like peptide-1 receptor agonist (GLP-1RA) is more effective as an up-titration strategy after dipeptidyl peptidase-4 inhibitor (DPP-4i)-based oral antidiabetic drug (OAD) therapy. GLP-1RAs can be...

Descripción completa

Detalles Bibliográficos
Autores principales: Miyagi, Masahiko, Uchino, Hiroshi, Kumashiro, Naoki, Higa, Mariko, Shin, Koki, Sasamoto, Makiko, Kitazato, Hiroji, Tamaki, Motoyuki, Matsuhisa, Munehide, Hirose, Takahisa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Healthcare 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6167274/
https://www.ncbi.nlm.nih.gov/pubmed/30121725
http://dx.doi.org/10.1007/s13300-018-0486-1
_version_ 1783360159466127360
author Miyagi, Masahiko
Uchino, Hiroshi
Kumashiro, Naoki
Higa, Mariko
Shin, Koki
Sasamoto, Makiko
Kitazato, Hiroji
Tamaki, Motoyuki
Matsuhisa, Munehide
Hirose, Takahisa
author_facet Miyagi, Masahiko
Uchino, Hiroshi
Kumashiro, Naoki
Higa, Mariko
Shin, Koki
Sasamoto, Makiko
Kitazato, Hiroji
Tamaki, Motoyuki
Matsuhisa, Munehide
Hirose, Takahisa
author_sort Miyagi, Masahiko
collection PubMed
description INTRODUCTION: It is unclear whether adding basal insulin or enhancing incretin signaling with a glucagon-like peptide-1 receptor agonist (GLP-1RA) is more effective as an up-titration strategy after dipeptidyl peptidase-4 inhibitor (DPP-4i)-based oral antidiabetic drug (OAD) therapy. GLP-1RAs can be injected without dose adjustment, unlike basal insulin. Our objective was to examine the efficacy of changing patients inadequately controlled with oral DPP-4i-based OAD therapy to injectable GLP-1RA and discontinuing the DPP4i versus adding basal insulin glargine (IGlar) with the continuation of the oral DPP4i. METHODS: Sixty patients with type 2 diabetes (T2DM) and glycated hemoglobin (HbA1c) between 7.0% and 10.0% on DPP-4i-based OAD therapy were randomized to either adding IGlar and remaining on the DPP-4i or liraglutide and discontinuing the DPP-4i for 24 weeks. Patients in the IGlar group started with 0.1 unit/kg and were titrated according to the algorithm. In the liraglutide group, the DPP-4i was replaced with liraglutide 0.9 mg/day, the maximum dose in Japan. We evaluated HbA1c, glycated albumin (GA), and anthropometrics. RESULTS: HbA1c was significantly lower at week 24 (− 1.0 ± 0.9% in the IGlar group and − 0.6 ± 0.8% in the liraglutide group), but the difference between groups was not significant. Changes in GA were similar (− 2.9 ± 3.2% vs. − 2.6 ± 3.2%) in both groups. Body weight (BW) was significantly lower only in the liraglutide group (+ 0.5 ± 2.6 kg vs. − 2.2 ± 2.0 kg). The rate of minor hypoglycemic episodes was similar for both groups. CONCLUSION: For poorly controlled T2DM on DPP-4i-based OAD therapy, switching to single-dose liraglutide to enhance incretin signaling is as effective as dose-titrated basal IGlar, but significant BW reduction was only seen in the liraglutide group. These results suggest that enhancing incretin signaling with a single-dose injectable GLP-1 RA might be an alternative to dose-titrated basal insulin therapy in patients with T2DM poorly controlled with DPP-4i-based OAD therapy. These findings should be confirmed in a longer and larger trial. TRIAL REGISTRATION: Trial Registry (UMIN-CTR) as UMIN000012224. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13300-018-0486-1) contains supplementary material, which is available to authorized users.
format Online
Article
Text
id pubmed-6167274
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Springer Healthcare
record_format MEDLINE/PubMed
spelling pubmed-61672742018-10-08 Up-Titration Strategy After DPP-4 Inhibitor-Based Oral Therapy for Type 2 Diabetes: A Randomized Controlled Trial Shifting to a Single-Dose GLP-1 Enhancer Versus Adding a Variable Basal Insulin Algorithm Miyagi, Masahiko Uchino, Hiroshi Kumashiro, Naoki Higa, Mariko Shin, Koki Sasamoto, Makiko Kitazato, Hiroji Tamaki, Motoyuki Matsuhisa, Munehide Hirose, Takahisa Diabetes Ther Original Research INTRODUCTION: It is unclear whether adding basal insulin or enhancing incretin signaling with a glucagon-like peptide-1 receptor agonist (GLP-1RA) is more effective as an up-titration strategy after dipeptidyl peptidase-4 inhibitor (DPP-4i)-based oral antidiabetic drug (OAD) therapy. GLP-1RAs can be injected without dose adjustment, unlike basal insulin. Our objective was to examine the efficacy of changing patients inadequately controlled with oral DPP-4i-based OAD therapy to injectable GLP-1RA and discontinuing the DPP4i versus adding basal insulin glargine (IGlar) with the continuation of the oral DPP4i. METHODS: Sixty patients with type 2 diabetes (T2DM) and glycated hemoglobin (HbA1c) between 7.0% and 10.0% on DPP-4i-based OAD therapy were randomized to either adding IGlar and remaining on the DPP-4i or liraglutide and discontinuing the DPP-4i for 24 weeks. Patients in the IGlar group started with 0.1 unit/kg and were titrated according to the algorithm. In the liraglutide group, the DPP-4i was replaced with liraglutide 0.9 mg/day, the maximum dose in Japan. We evaluated HbA1c, glycated albumin (GA), and anthropometrics. RESULTS: HbA1c was significantly lower at week 24 (− 1.0 ± 0.9% in the IGlar group and − 0.6 ± 0.8% in the liraglutide group), but the difference between groups was not significant. Changes in GA were similar (− 2.9 ± 3.2% vs. − 2.6 ± 3.2%) in both groups. Body weight (BW) was significantly lower only in the liraglutide group (+ 0.5 ± 2.6 kg vs. − 2.2 ± 2.0 kg). The rate of minor hypoglycemic episodes was similar for both groups. CONCLUSION: For poorly controlled T2DM on DPP-4i-based OAD therapy, switching to single-dose liraglutide to enhance incretin signaling is as effective as dose-titrated basal IGlar, but significant BW reduction was only seen in the liraglutide group. These results suggest that enhancing incretin signaling with a single-dose injectable GLP-1 RA might be an alternative to dose-titrated basal insulin therapy in patients with T2DM poorly controlled with DPP-4i-based OAD therapy. These findings should be confirmed in a longer and larger trial. TRIAL REGISTRATION: Trial Registry (UMIN-CTR) as UMIN000012224. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13300-018-0486-1) contains supplementary material, which is available to authorized users. Springer Healthcare 2018-08-18 2018-10 /pmc/articles/PMC6167274/ /pubmed/30121725 http://dx.doi.org/10.1007/s13300-018-0486-1 Text en © The Author(s) 2018 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Research
Miyagi, Masahiko
Uchino, Hiroshi
Kumashiro, Naoki
Higa, Mariko
Shin, Koki
Sasamoto, Makiko
Kitazato, Hiroji
Tamaki, Motoyuki
Matsuhisa, Munehide
Hirose, Takahisa
Up-Titration Strategy After DPP-4 Inhibitor-Based Oral Therapy for Type 2 Diabetes: A Randomized Controlled Trial Shifting to a Single-Dose GLP-1 Enhancer Versus Adding a Variable Basal Insulin Algorithm
title Up-Titration Strategy After DPP-4 Inhibitor-Based Oral Therapy for Type 2 Diabetes: A Randomized Controlled Trial Shifting to a Single-Dose GLP-1 Enhancer Versus Adding a Variable Basal Insulin Algorithm
title_full Up-Titration Strategy After DPP-4 Inhibitor-Based Oral Therapy for Type 2 Diabetes: A Randomized Controlled Trial Shifting to a Single-Dose GLP-1 Enhancer Versus Adding a Variable Basal Insulin Algorithm
title_fullStr Up-Titration Strategy After DPP-4 Inhibitor-Based Oral Therapy for Type 2 Diabetes: A Randomized Controlled Trial Shifting to a Single-Dose GLP-1 Enhancer Versus Adding a Variable Basal Insulin Algorithm
title_full_unstemmed Up-Titration Strategy After DPP-4 Inhibitor-Based Oral Therapy for Type 2 Diabetes: A Randomized Controlled Trial Shifting to a Single-Dose GLP-1 Enhancer Versus Adding a Variable Basal Insulin Algorithm
title_short Up-Titration Strategy After DPP-4 Inhibitor-Based Oral Therapy for Type 2 Diabetes: A Randomized Controlled Trial Shifting to a Single-Dose GLP-1 Enhancer Versus Adding a Variable Basal Insulin Algorithm
title_sort up-titration strategy after dpp-4 inhibitor-based oral therapy for type 2 diabetes: a randomized controlled trial shifting to a single-dose glp-1 enhancer versus adding a variable basal insulin algorithm
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6167274/
https://www.ncbi.nlm.nih.gov/pubmed/30121725
http://dx.doi.org/10.1007/s13300-018-0486-1
work_keys_str_mv AT miyagimasahiko uptitrationstrategyafterdpp4inhibitorbasedoraltherapyfortype2diabetesarandomizedcontrolledtrialshiftingtoasingledoseglp1enhancerversusaddingavariablebasalinsulinalgorithm
AT uchinohiroshi uptitrationstrategyafterdpp4inhibitorbasedoraltherapyfortype2diabetesarandomizedcontrolledtrialshiftingtoasingledoseglp1enhancerversusaddingavariablebasalinsulinalgorithm
AT kumashironaoki uptitrationstrategyafterdpp4inhibitorbasedoraltherapyfortype2diabetesarandomizedcontrolledtrialshiftingtoasingledoseglp1enhancerversusaddingavariablebasalinsulinalgorithm
AT higamariko uptitrationstrategyafterdpp4inhibitorbasedoraltherapyfortype2diabetesarandomizedcontrolledtrialshiftingtoasingledoseglp1enhancerversusaddingavariablebasalinsulinalgorithm
AT shinkoki uptitrationstrategyafterdpp4inhibitorbasedoraltherapyfortype2diabetesarandomizedcontrolledtrialshiftingtoasingledoseglp1enhancerversusaddingavariablebasalinsulinalgorithm
AT sasamotomakiko uptitrationstrategyafterdpp4inhibitorbasedoraltherapyfortype2diabetesarandomizedcontrolledtrialshiftingtoasingledoseglp1enhancerversusaddingavariablebasalinsulinalgorithm
AT kitazatohiroji uptitrationstrategyafterdpp4inhibitorbasedoraltherapyfortype2diabetesarandomizedcontrolledtrialshiftingtoasingledoseglp1enhancerversusaddingavariablebasalinsulinalgorithm
AT tamakimotoyuki uptitrationstrategyafterdpp4inhibitorbasedoraltherapyfortype2diabetesarandomizedcontrolledtrialshiftingtoasingledoseglp1enhancerversusaddingavariablebasalinsulinalgorithm
AT matsuhisamunehide uptitrationstrategyafterdpp4inhibitorbasedoraltherapyfortype2diabetesarandomizedcontrolledtrialshiftingtoasingledoseglp1enhancerversusaddingavariablebasalinsulinalgorithm
AT hirosetakahisa uptitrationstrategyafterdpp4inhibitorbasedoraltherapyfortype2diabetesarandomizedcontrolledtrialshiftingtoasingledoseglp1enhancerversusaddingavariablebasalinsulinalgorithm