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Comparison of the effect on glycemic control between imeglimin and metformin in patients with type 2 diabetes -prospective randomized controlled trial-

Study for the effects of imeglimin on glycemic control in patients with type 2 diabetes

73

The total number of enrolled cases was 73, comprising 37 in the imeglimin add-on group and 36 in the metformin dose-escalation group. Of these, 8 cases were excluded due to protocol deviations, withdrawal of consent, or discontinuation of follow-up. Consequently, the maximum analysis population comprised 65 cases, with 33 in the imeglimin add-on group and 32 in the metformin dose-escalation group. Furthermore, 8 additional cases were excluded due to the occurrence of adverse events, leaving 57 cases who completed the study (26 in the imeglimin add-on group and 31 in the metformin dose-escalation group). The baseline characteristics of the imeglimin add-on group (n = 33) included 11 females (33.3%), a mean age of 66.9 +- 14.1 years, and an HbA1c level of 7.61 +- 0.48. For the metformin dose-escalation group (n = 32), baseline characteristics included 13 females (40.6%), a mean age of 66.2 +- 14.3 years, and an HbA1c level of 7.56 +- 0.61.

The enrollment pace was generally consistent with initial projections. Patient recruitment was conducted across all participating institutions except for one, with the majority of cases registered at Hokkaido University Hospital. The distribution of registered cases was as follows: Hokkaido University Hospital (18 cases), Aoki Clinic (6 cases), Kurihara Clinic (28 cases), Yokoyama Clinic (12 cases), Manda Memorial Hospital (2 cases), NTT East Sapporo Hospital (3 cases), Tomakomai City Hospital (2 cases), and Sapporo City General Hospital (2 cases). Although the target enrollment was set at 70 cases, an additional three patients who had verbally expressed their intention to participate at the time of reaching the target were also included, resulting in a total of 73 registered cases.

No serious adverse events or severe illnesses occurred during the study. However, several adverse events were reported. In the imeglimin add-on group, nausea was observed in 7 cases (18.9%), diarrhea in 4 cases (10.8%), and hypoglycemia in 1 case (2.7%). In the metformin dose-escalation group, nausea and diarrhea were each observed in 1 case (2.8%). Among these, 5 patients with nausea and 3 patients with diarrhea discontinued the study. In these discontinued cases, symptoms improved upon discontinuation of imeglimin or dose reduction of metformin. Importantly, no cases of severe hypoglycemia were reported in either group.

Among the secondary endpoints, although significant weight loss was observed in the imeglimin group during the study period, this change was not significant when compared with the body weight reduction in the metformin group. Regarding hepatic function, improvement in hepatobiliary enzymes (AST, ALT, and gamma GTP) was observed in the imeglimin group, and the change in AST after 24 weeks was significant in intergroup comparisons. The fatty liver index (FLI) was significantly reduced in both groups but did not differ between the groups. Additionally, in the imeglimin group, significant correlations were found between the improvement in HbA1c and reductions in liver enzymes and FLI.

The addition of imeglimin was more beneficial for glycemic management compared to the metformin dose escalation regimen.

Jan. 31, 2025

Dec. 26, 2024

https://dom-pubs.pericles-prod.literatumonline.com/doi/10.1111/dom.16150

No

There are no particular plans.

https://jrct.niph.go.jp/latest-detail/jRCT1011220005

Nakamura Akinobu

Hokkaido University Hospital

N-15, W-7, Kita-ku, Sapporo, Hokkaido 060-8638, Japan

akinbo@huhp.hokudai.ac.jp

Nakamura Akinobu

Hokkaido University

N-15, W-7, Kita-ku, Sapporo, Hokkaido 060-8638, Japan

+81-11-706-5915

hnomoto@med.hokudai.ac.jp

Complete

May. 11, 2022

Interventional

randomized controlled trial

open(masking not used)

active control

parallel assignment

treatment purpose

1) Age 20-90 years old
2) HbA1c 7.0-10.0%
3) patients who were treated with DPP-4 inhibitors at least for 12 weeks (Sitagliptin, teneligliptin, and anagliptin: from regular dose to maximun dose; vildagliptin, saxagliptin, trelagliptin, linagliptin, alogliptin, and omarigliptin: regular dose)
4) written informed consent

1) history of anaphylaxis of imeglimin
2) inappropriate to increase metformin
3) unstable retinopathy
4) severe hepatic dysfunction, renal dysfunction (eGFR<45 mL/min/1.73m2), or heart failure
5) female patients who are pregnant and/or willing to be pregnant
6) severe ketosis, diabetic coma
7) severe infection, surgery, serious trauma
8) inability to consume an appropriate diet
9) incompatibility with the trial for other reasons, as determined by a physician

Both

type 2 diabetes

Addition of imeglimin 2,000 mg/day or increase metformin up to 1,000-2,000 mg/day (doubling). Participants in metformin group follow an escalation regimen of metformin (from 500 mg/day to 1,000 mg/day, from 750 mg/day to 1,500 mg/day, from 1,000 mg/day to 2,000 mg/day (maintenance dose reached after more than 4 weeks of 1,500 mg of metformin)). Metformin can be increased up to 2,250 mg/day in metformin group, however, maximum dose is limited to 1,500 mg/day in case of impaired GFR (45-60 mL/min/1.73m2) and/or 75 years old and above.

The change in HbA1c at 24 weeks from baseline

1) The change in the other blood and urinary tests
2) The change in weight, abdominal circumference, blood pressure and pulse
3) The change in indices of insulin secretion and insulin resistance
4) The change in scores of fatty liver disease
5) Adverse effects
6) The factors associated with improvement of HbA1c and secondary endopoints

+81-11-706-7934

April. 26, 2022

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