Efficacy of DPP-4 inhibitors, GLP-1 analogues, and SGLT2 inhibitors as add-ons to metformin monotherapy in T2DM patients: a model-based meta-analysis

Hiroyuki Inoue, Yoko Tamaki, Yushi Kashihara, Shota Muraki, Makoto Kakara, Takeshi Hirota, Ichiro Ieiri

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Aims: The aim of the present study was to quantitate the hypoglycaemic effects of dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP-1r) and sodium glucose cotransporter 2 inhibitors (SGLT2i) as add-on treatments to metformin monotherapy in patients with type 2 diabetes mellitus (T2DM) using a model-based meta-analysis (MBMA). Methods: A systematic literature search of public databases was conducted to develop models that describe the time courses of the fasting plasma glucose (FPG)- and haemoglobin A1c (HbA1c)-lowering effects of three antidiabetic classes using NONMEM 7.3.0. Results: Seventy-six publications were eligible for this study, and 873 FPG and 1086 HbA1c values were collected. We developed a physiological indirect response model that described the time courses of FPG and HbA1c and simulated reductions in these values 90 days after the initiation of add-on treatments. FPG and HbA1c reductions with once weekly exenatide, liraglutide and dulaglutide were greater than those with other drugs. Mean changes from baseline FPG and HbA1c with these drugs were as follows: exenatide (−22.5 and −16.6%), liraglutide (−22.1 and −16.3%), and dulaglutide (−19.3 and −14.3%). The hypoglycaemic effects of DPP-4i and SGLT2i were similar. Conclusions: Once weekly exenatide, liraglutide and dulaglutide provided better hypoglycaemic effects among the antidiabetic drugs analysed. Long-acting GLP-1r appears to be more useful for T2DM patients inadequately controlled with metformin monotherapy.

Original languageEnglish
Pages (from-to)393-402
Number of pages10
JournalBritish journal of clinical pharmacology
Volume85
Issue number2
DOIs
Publication statusPublished - Feb 1 2019

Fingerprint

Glucagon-Like Peptide 1
Metformin
Hypoglycemic Agents
Type 2 Diabetes Mellitus
Meta-Analysis
Fasting
Hemoglobins
Glucose
Sodium-Glucose Transport Proteins
Dipeptidyl-Peptidase IV Inhibitors
Pharmaceutical Preparations
Publications
Databases
Therapeutics
Liraglutide
exenatide
dulaglutide

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

Cite this

Efficacy of DPP-4 inhibitors, GLP-1 analogues, and SGLT2 inhibitors as add-ons to metformin monotherapy in T2DM patients : a model-based meta-analysis. / Inoue, Hiroyuki; Tamaki, Yoko; Kashihara, Yushi; Muraki, Shota; Kakara, Makoto; Hirota, Takeshi; Ieiri, Ichiro.

In: British journal of clinical pharmacology, Vol. 85, No. 2, 01.02.2019, p. 393-402.

Research output: Contribution to journalArticle

@article{cdda5dcd6c7b4b678c4c59cf6f1565de,
title = "Efficacy of DPP-4 inhibitors, GLP-1 analogues, and SGLT2 inhibitors as add-ons to metformin monotherapy in T2DM patients: a model-based meta-analysis",
abstract = "Aims: The aim of the present study was to quantitate the hypoglycaemic effects of dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP-1r) and sodium glucose cotransporter 2 inhibitors (SGLT2i) as add-on treatments to metformin monotherapy in patients with type 2 diabetes mellitus (T2DM) using a model-based meta-analysis (MBMA). Methods: A systematic literature search of public databases was conducted to develop models that describe the time courses of the fasting plasma glucose (FPG)- and haemoglobin A1c (HbA1c)-lowering effects of three antidiabetic classes using NONMEM 7.3.0. Results: Seventy-six publications were eligible for this study, and 873 FPG and 1086 HbA1c values were collected. We developed a physiological indirect response model that described the time courses of FPG and HbA1c and simulated reductions in these values 90 days after the initiation of add-on treatments. FPG and HbA1c reductions with once weekly exenatide, liraglutide and dulaglutide were greater than those with other drugs. Mean changes from baseline FPG and HbA1c with these drugs were as follows: exenatide (−22.5 and −16.6{\%}), liraglutide (−22.1 and −16.3{\%}), and dulaglutide (−19.3 and −14.3{\%}). The hypoglycaemic effects of DPP-4i and SGLT2i were similar. Conclusions: Once weekly exenatide, liraglutide and dulaglutide provided better hypoglycaemic effects among the antidiabetic drugs analysed. Long-acting GLP-1r appears to be more useful for T2DM patients inadequately controlled with metformin monotherapy.",
author = "Hiroyuki Inoue and Yoko Tamaki and Yushi Kashihara and Shota Muraki and Makoto Kakara and Takeshi Hirota and Ichiro Ieiri",
year = "2019",
month = "2",
day = "1",
doi = "10.1111/bcp.13807",
language = "English",
volume = "85",
pages = "393--402",
journal = "British Journal of Clinical Pharmacology",
issn = "0306-5251",
publisher = "Wiley-Blackwell",
number = "2",

}

TY - JOUR

T1 - Efficacy of DPP-4 inhibitors, GLP-1 analogues, and SGLT2 inhibitors as add-ons to metformin monotherapy in T2DM patients

T2 - a model-based meta-analysis

AU - Inoue, Hiroyuki

AU - Tamaki, Yoko

AU - Kashihara, Yushi

AU - Muraki, Shota

AU - Kakara, Makoto

AU - Hirota, Takeshi

AU - Ieiri, Ichiro

PY - 2019/2/1

Y1 - 2019/2/1

N2 - Aims: The aim of the present study was to quantitate the hypoglycaemic effects of dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP-1r) and sodium glucose cotransporter 2 inhibitors (SGLT2i) as add-on treatments to metformin monotherapy in patients with type 2 diabetes mellitus (T2DM) using a model-based meta-analysis (MBMA). Methods: A systematic literature search of public databases was conducted to develop models that describe the time courses of the fasting plasma glucose (FPG)- and haemoglobin A1c (HbA1c)-lowering effects of three antidiabetic classes using NONMEM 7.3.0. Results: Seventy-six publications were eligible for this study, and 873 FPG and 1086 HbA1c values were collected. We developed a physiological indirect response model that described the time courses of FPG and HbA1c and simulated reductions in these values 90 days after the initiation of add-on treatments. FPG and HbA1c reductions with once weekly exenatide, liraglutide and dulaglutide were greater than those with other drugs. Mean changes from baseline FPG and HbA1c with these drugs were as follows: exenatide (−22.5 and −16.6%), liraglutide (−22.1 and −16.3%), and dulaglutide (−19.3 and −14.3%). The hypoglycaemic effects of DPP-4i and SGLT2i were similar. Conclusions: Once weekly exenatide, liraglutide and dulaglutide provided better hypoglycaemic effects among the antidiabetic drugs analysed. Long-acting GLP-1r appears to be more useful for T2DM patients inadequately controlled with metformin monotherapy.

AB - Aims: The aim of the present study was to quantitate the hypoglycaemic effects of dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP-1r) and sodium glucose cotransporter 2 inhibitors (SGLT2i) as add-on treatments to metformin monotherapy in patients with type 2 diabetes mellitus (T2DM) using a model-based meta-analysis (MBMA). Methods: A systematic literature search of public databases was conducted to develop models that describe the time courses of the fasting plasma glucose (FPG)- and haemoglobin A1c (HbA1c)-lowering effects of three antidiabetic classes using NONMEM 7.3.0. Results: Seventy-six publications were eligible for this study, and 873 FPG and 1086 HbA1c values were collected. We developed a physiological indirect response model that described the time courses of FPG and HbA1c and simulated reductions in these values 90 days after the initiation of add-on treatments. FPG and HbA1c reductions with once weekly exenatide, liraglutide and dulaglutide were greater than those with other drugs. Mean changes from baseline FPG and HbA1c with these drugs were as follows: exenatide (−22.5 and −16.6%), liraglutide (−22.1 and −16.3%), and dulaglutide (−19.3 and −14.3%). The hypoglycaemic effects of DPP-4i and SGLT2i were similar. Conclusions: Once weekly exenatide, liraglutide and dulaglutide provided better hypoglycaemic effects among the antidiabetic drugs analysed. Long-acting GLP-1r appears to be more useful for T2DM patients inadequately controlled with metformin monotherapy.

UR - http://www.scopus.com/inward/record.url?scp=85058059732&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85058059732&partnerID=8YFLogxK

U2 - 10.1111/bcp.13807

DO - 10.1111/bcp.13807

M3 - Article

C2 - 30394576

AN - SCOPUS:85058059732

VL - 85

SP - 393

EP - 402

JO - British Journal of Clinical Pharmacology

JF - British Journal of Clinical Pharmacology

SN - 0306-5251

IS - 2

ER -