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Meta-Analysis
. 2023 Nov;14(11):1246-1261.
doi: 10.1111/jdi.14070. Epub 2023 Aug 23.

Efficacy, safety and tolerability of imeglimin in patients with type 2 diabetes mellitus: A meta-analysis of randomized controlled trials

Katsuhiko Hagi  1 , Masahiro Nitta  1 , Hirotaka Watada  2 , Kohei Kaku  3 , Kohjiro Ueki  4
Affiliations
Meta-Analysis

Efficacy, safety and tolerability of imeglimin in patients with type 2 diabetes mellitus: A meta-analysis of randomized controlled trials

Katsuhiko Hagi et al. J Diabetes Investig. 2023 Nov.

Abstract

Aims/introduction: This meta-analysis aimed to evaluate the efficacy and safety/tolerability of imeglimin, a novel oral antihyperglycemic agent, administered as monotherapy and adjunctive therapy in patients with type 2 diabetes mellitus.

Materials and methods: Parallel-group randomized controlled trials comparing imeglimin with placebo in adults with type 2 diabetes mellitus were included. Risk ratios or weighted mean differences (WMD) and 95% confidence intervals (CIs) were calculated using random effects models. The primary outcome for efficacy was the change in glycated hemoglobin (HbA1c). Secondary outcomes included other efficacy-related outcomes, specific adverse events, and changes in body weight and lipid parameters.

Results: Nine randomized controlled trials (n = 1,655) were included. When analyzed by dose, there was a significant difference in glycated hemoglobin (%) between imeglimin monotherapy and placebo at doses >1,000 mg twice daily (1,000 mg: studies N = 3, patients n = 517, WMD = -0.714, P < 0.001; 1,500 mg: N = 5, n = 448, WMD = -0.531, P = 0.020; 2,000 mg: N = 1, n = 149, WMD = -0.450, P = 0.005). Imeglimin adjunctive therapy significantly improved glycated hemoglobin over placebo at doses of 1,000 mg (N = 1, n = 214, WMD = -0.600, P < 0.001) and 1,500 mg (N = 2, n = 324, WMD = -0.576, P < 0.001). Subgroup analysis of the primary outcome showed that imeglimin was effective regardless of chronic kidney disease category, with studies carried out in Japan and in patients with lower body mass index showing a trend toward improved imeglimin efficacy. There were no significant differences between imeglimin and placebo in the risk of all-cause discontinuation and the proportion of patients who presented with at least one adverse event.

Conclusions: Imeglimin is efficacious, safe, and well tolerated as monotherapy and adjunctive therapy.

Keywords: Imeglimin; Meta-analysis; Type 2 diabetes mellitus.

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Conflict of interest statement

KH and MN are employees of Sumitomo Pharma Co., Ltd. HW has received fees for medical writing support from Novo Nordisk; grants from Astellas Pharma, AstraZeneca, Daiichi Sankyo, Eli Lilly Japan, Johnson & Johnson, Kowa, Kyowa Hakko Kirin, Merck Sharp & Dohme, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Nippon Boehringer Ingelheim, Novartis Pharma, Novo Nordisk Pharma, Ono Pharmaceutical, Pfizer Japan, Sanofi, Sumitomo Dainippon Pharma, Taisho Toyama Pharmaceutical, Takeda Pharmaceutical and Terumo; and speaker fees from Astellas Pharma, AstraZeneca, Eli Lilly Japan, Fujifilm Pharma, Kissei Pharmaceutical, Kowa Pharmaceutical, Merck Sharp & Dohme, Mitsubishi Tanabe Pharma, Nippon Boehringer Ingelheim, Novartis, Novo Nordisk, Ono Pharmaceutical, Sanofi, Sanwa Kagaku Kenkyusho, Sumitomo Dainippon Pharma and Takeda Pharmaceutical. KK has received grants from Nippon Boehringer Ingelheim, Taisho Pharmaceutical and Mitsubishi Tanabe Pharma; consulting fees from Sanwa Kagaku Kenkyusho; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Astellas, Taisho Pharmaceutical, Nippon Boehringer Ingelheim, Mitsubishi Tanabe Pharma, Sumitomo Pharma, Elli Lily Japan, Kowa and Novo Nordisk Pharma. KU has received grants from Boehringer Ingelheim, Mitsubishi Tanabe, Sumitomo Pharma, Sanofi, Novo Nordisk, Kyowa‐Kirin, Ono Pharmaceutical and Takeda Pharmaceutical; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Novo Nordisk, Mitsubishi Tanabe, AstraZeneca, Eli Lilly, Ono Pharmaceutical, Sumitomo Pharma, Kowa, Daiichi Sankyo, Taisho Pharmaceutical, Boehringer Ingelheim and Bayer; and has participated in a Data Safety Monitoring Board or Advisory Board for Abbott, Kyowa‐Kirin, Bayer, Terumo, AstraZeneca, Eli Lilly, Sumitomo Pharma, Mitsubishi Tanabe and Novo Nordisk. HW, KK and KU are Editorial Board members of Journal of Diabetes Investigation, and co‐authors of this article. To minimize bias, they were excluded from all editorial decision‐making related to the acceptance of this article for publication.

Approval of the research protocol: N/A.

Informed consent: N/A.

Registry and the registration no. of the study/trial: The study protocol was registered at OSF on 2022‐03‐27 (https://osf.io/t2nuw/).

Animal studies: N/A.

Figures

Figure 1
Figure 1
Flow diagram describing the search process. †Excluded for being clearly not relevant or a duplicate search result.
Figure 2
Figure 2
Forest plot of the weighted mean difference (WMD) for changed glycated hemoglobin (%) by imeglimin dose (monotherapy) (a) and forest plot of the WMD for changed glycated hemoglobin (%) by imeglimin dose (adjunctive therapy) (b). b.i.d., twice daily; CI, confidence interval.
See this image and copyright information in PMC

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