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
Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Division of Endocrinology, Metabolism, and Rheumatology, Department of Internal Medicine, Asahikawa Medical University, Asahikawa, Japan.
Diabetes Obes Metab. 2025 Mar;27(3):1466-1476. doi: 10.1111/dom.16150. Epub 2024 Dec 26.
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).
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.
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.
Imeglimin in combination with a dipeptidyl peptidase-4 inhibitor and low-dose metformin improved HbA1c compared with metformin dose escalation.
比较在接受二肽基肽酶-4抑制剂加低剂量二甲双胍（500 - 1000毫克/天）治疗的2型糖尿病患者中，添加依美格列明与增加二甲双胍剂量对血糖控制的疗效。
在这项多中心、开放标签、前瞻性、随机、平行组比较研究中，符合条件的受试者接受依美格列明（2000毫克/天）添加治疗或二甲双胍剂量递增治疗24周。主要终点是24周内糖化血红蛋白（HbA1c）的平均变化。作为次要终点，分析不良事件的发生情况、代谢参数变化、生物标志物以及与HbA1c改善相关的因素。
共纳入73名符合条件的受试者。其中，65名参与者组成完整分析集。在24周时，与二甲双胍剂量递增组（n = 32）相比，添加依美格列明组（n = 33）的HbA1c改善更显著（依美格列明组从7.61±0.48%降至6.93±0.49%，二甲双胍剂量递增组从7.56±0.61%降至7.09±0.56%；变化差异：-0.21%[95%置信区间：-0.41%，-0.01%][p = 0.038]）；然而，依美格列明组有7名受试者因严重胃肠道不良事件停用依美格列明。在组内治疗前后比较中，依美格列明治疗显著降低体重并改善肝酶升高。依美格列明组中，HbA1c改善水平与脂肪肝疾病指标之间存在显著相关性。
与二甲双胍剂量递增相比，依美格列明联合二肽基肽酶-4抑制剂和低剂量二甲双胍可改善HbA1c。
