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).

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.