PMID- 37293502
OWN - NLM
STAT- MEDLINE
DCOM- 20230612
LR  - 20240227
IS  - 1664-2392 (Print)
IS  - 1664-2392 (Electronic)
IS  - 1664-2392 (Linking)
VI  - 14
DP  - 2023
TI  - Efficacy of combination therapy with GABA, a DPP-4i and a PPI as an adjunct to 
      insulin therapy in patients with type 1 diabetes.
PG  - 1171886
LID - 10.3389/fendo.2023.1171886 [doi]
LID - 1171886
AB  - INTRODUCTION: The purpose of this retrospective clinic chart review study was to 
      determine the potential of a combination therapy (CT) consisting of 
      gamma-aminobutyric acid (GABA), a dipeptidyl peptidase-4 inhibitor (DPP-4i), and a 
      proton pump inhibitor (PPI) to improve glycemic control as an adjunct to insulin 
      therapy in patients with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: 
      Nineteen patients with T1D on insulin therapy were treated with additional CT in 
      oral form. Fasting blood glucose (FBG), HbA1c, insulin dose-adjusted HbA1c 
      (IDA-A1c), daily insulin dose, insulin/weight ratio (IWR), and fasting plasma 
      C-peptide were measured after 26-42 weeks of treatments. RESULTS: FBG, HbA1c, 
      IDA-A1c, insulin dose and IWR were all significantly decreased while plasma 
      C-peptide was significantly increased by the CT. Treatment outcomes were further 
      analyzed by separation of the 19 patients into two groups. One group started on 
      the CT within 12 months of insulin treatment (early therapy, 10 patients) and 
      another group started on this therapy only after 12 months of insulin treatment 
      (late therapy, 9 patients). FBG, IDA-A1c, insulin dose, and IWR decreased 
      significantly in both the early and late CT groups, however to a better extent in 
      the early therapy group. Moreover, plasma C-peptide increased significantly only 
      in the early therapy group, and 7 of the 10 patients in this group were able to 
      discontinue insulin treatment while maintaining good glycemic control to study 
      end compared with none of the 9 patients in the late therapy group. CONCLUSION: 
      These results support the concept that the combination of GABA, a DPP-4i and a 
      PPI as an adjunct to insulin therapy improves glycemic control in patients with 
      T1D, and that the insulin dose required for glycemic control can be reduced or 
      even eliminated in some patients receiving this novel therapy.
CI  - Copyright (c) 2023 Rabinovitch, Koshelev, Lagunas-Rangel, Kosheleva, Gavra, Schioth 
      and Levit.
FAU - Rabinovitch, Alexander
AU  - Rabinovitch A
AD  - Kelowna, BC, Canada.
FAU - Koshelev, Daniil
AU  - Koshelev D
AD  - Department of Surgical Sciences, Functional Pharmacology and Neuroscience, 
      Uppsala University, Uppsala, Sweden.
AD  - Levicure LTD, Rishon Lezion, Israel.
FAU - Lagunas-Rangel, Francisco Alejandro
AU  - Lagunas-Rangel FA
AD  - Department of Surgical Sciences, Functional Pharmacology and Neuroscience, 
      Uppsala University, Uppsala, Sweden.
FAU - Kosheleva, Liudmila
AU  - Kosheleva L
AD  - Department of Surgical Sciences, Functional Pharmacology and Neuroscience, 
      Uppsala University, Uppsala, Sweden.
AD  - Levicure LTD, Rishon Lezion, Israel.
FAU - Gavra, Tali
AU  - Gavra T
AD  - Research Unit, Assuta Medical Centers, Tel Aviv, Israel.
FAU - Schioth, Helgi B
AU  - Schioth HB
AD  - Department of Surgical Sciences, Functional Pharmacology and Neuroscience, 
      Uppsala University, Uppsala, Sweden.
FAU - Levit, Shmuel
AU  - Levit S
AD  - Levicure LTD, Rishon Lezion, Israel.
AD  - Diabetes and Metabolism Institute, Assuta Medical Centers, Tel Aviv, Israel.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230524
PL  - Switzerland
TA  - Front Endocrinol (Lausanne)
JT  - Frontiers in endocrinology
JID - 101555782
RN  - 0 (Dipeptidyl-Peptidase IV Inhibitors)
RN  - 0 (Insulin)
RN  - 0 (Glycated Hemoglobin)
RN  - 0 (Proton Pump Inhibitors)
RN  - 0 (C-Peptide)
RN  - 0 (Blood Glucose)
RN  - 0 (Hypoglycemic Agents)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
SB  - IM
MH  - Humans
MH  - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use
MH  - Insulin/therapeutic use
MH  - *Diabetes Mellitus, Type 1/drug therapy/chemically induced
MH  - Glycated Hemoglobin
MH  - Proton Pump Inhibitors/therapeutic use
MH  - Retrospective Studies
MH  - C-Peptide
MH  - *Diabetes Mellitus, Type 2/drug therapy
MH  - Blood Glucose
MH  - Hypoglycemic Agents/therapeutic use
MH  - gamma-Aminobutyric Acid/therapeutic use
PMC - PMC10246767
OTO - NOTNLM
OT  - DPP-4i
OT  - GABA
OT  - PPI
OT  - insulin
OT  - type 1 diabetes
COIS- Authors SL, DK, and LK are members of Levicure LTD and have patents related to 
      the triple combination of GABA, DPP-4i, and PPI. The remaining authors declare 
      that the research was conducted in the absence of any commercial or financial 
      relationships that could be construed as a potential conflict of interest.
EDAT- 2023/06/09 06:42
MHDA- 2023/06/12 06:42
PMCR- 2023/01/01
CRDT- 2023/06/09 04:36
PHST- 2023/02/22 00:00 [received]
PHST- 2023/05/09 00:00 [accepted]
PHST- 2023/06/12 06:42 [medline]
PHST- 2023/06/09 06:42 [pubmed]
PHST- 2023/06/09 04:36 [entrez]
PHST- 2023/01/01 00:00 [pmc-release]
AID - 10.3389/fendo.2023.1171886 [doi]
PST - epublish
SO  - Front Endocrinol (Lausanne). 2023 May 24;14:1171886. doi: 
      10.3389/fendo.2023.1171886. eCollection 2023.