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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
Author(s) -
Inoue Hiroyuki,
Tamaki Yoko,
Kashihara Yushi,
Muraki Shota,
Kakara Makoto,
Hirota Takeshi,
Ieiri Ichiro
Publication year - 2019
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.13807
Subject(s) - dulaglutide , exenatide , metformin , liraglutide , medicine , dipeptidyl peptidase 4 , pharmacology , type 2 diabetes , sitagliptin , type 2 diabetes mellitus , diabetes mellitus , endocrinology
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.