Efficacy of imeglimin treatment versus metformin dose escalation on glycemic control in subjects with type 2 diabetes treated with a dipeptidyl peptidase‐4 inhibitor plus low‐dose metformin: A multicenter, prospective, randomized, open‐label, parallel‐group comparison study (MEGMI study)

• Published in: Diabetes, obesity & metabolism Vol. 27; no. 3; pp. 1466 - 1476
• Main Authors: Takahashi, Akihiro, Nomoto, Hiroshi, Yokoyama, Hiroki, Yokozeki, Kei, Furusawa, Sho, Oe, Yuki, Kameda, Reina, Kawata, Shinichiro, Miyoshi, Arina, Nagai, So, Miya, Aika, Kameda, Hiraku, Nakamura, Akinobu, Atsumi, Tatsuya
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.03.2025; Wiley Subscription Services, Inc
• Subjects: Adverse events; Aged; Blood Glucose - drug effects; Blood Glucose - metabolism; Body weight; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Dipeptidyl-Peptidase IV Inhibitors - administration & dosage; Dipeptidyl-Peptidase IV Inhibitors - adverse effects; Dipeptidyl-Peptidase IV Inhibitors - therapeutic use; Dose-Response Relationship, Drug; DPP‐IV inhibitor; Drug Therapy, Combination; Fatty liver; Female; Gastrointestinal tract; Glycated Hemoglobin - analysis; Glycated Hemoglobin - metabolism; Glycemic Control - methods; Hemoglobin; Humans; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - adverse effects; Hypoglycemic Agents - therapeutic use; imeglimin; Liver diseases; Male; Metformin; Metformin - administration & dosage; Metformin - adverse effects; Metformin - therapeutic use; Middle Aged; Peptidase; Prospective Studies; randomised trial; Treatment Outcome; Triazines; type 2 diabetes; metformin; imeglimin; randomised trial; type 2 diabetes; DPP‐IV inhibitor
• ISSN: 1462-8902; 1463-1326; 1463-1326
• DOI: 10.1111/dom.16150

Aims To compare the efficacy of adding imeglimin versus that of metformin dose escalation on glycemic control in subjects with type 2 diabetes treated with a dipeptidyl peptidase‐4 inhibitor plus low‐dose metformin (500–1000 mg/day). Materials and Methods In this multicentre, open‐labelled, prospective, randomized, parallel‐group comparison study, the addition of imeglimin (2000 mg/day) or metformin escalation was applied for 24 weeks in eligible subjects. The primary endpoint was the mean change in glycated haemoglobin (HbA1c) over 24 weeks. As the secondary endpoints, the occurrence of adverse events, changes in metabolic parameters, biomarkers and factors associated with HbA1c improvement were analysed. Results Seventy‐three eligible subjects were enrolled. Of them, 65 participants comprised the full analysis set. At 24 weeks, the addition of imeglimin (n = 33) resulted in greater improvement in HbA1c compared with metformin dose escalation (n = 32) (from 7.61 ± 0.48% to 6.93 ± 0.49% in imeglimin and from 7.56 ± 0.61% to 7.09 ± 0.56% in metformin escalation; change difference: −0.21% [95% confidence interval: −0.41%, −0.01%] [p = 0.038]); however, seven subjects in the imeglimin group discontinued imeglimin because of serious adverse events on gastrointestinal tract. In intra‐group pre/post comparisons, imeglimin treatment significantly reduced body weight and improved liver enzyme elevation. There was a significant correlation between improvement levels of HbA1c and indicators of fatty liver disease in the imeglimin group. Conclusions Imeglimin in combination with a dipeptidyl peptidase‐4 inhibitor and low‐dose metformin improved HbA1c compared with metformin dose escalation.