Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Clinical and Translational Research Center, Kobe University Hospital, Kobe, Japan.
J Diabetes Investig. 2024 Sep;15(9):1211-1219. doi: 10.1111/jdi.14226. Epub 2024 May 4.
AIMS/INTRODUCTION: Insulin resistance syndrome and lipoatrophic diabetes are rare conditions characterized by the development of treatment-refractory diabetes with severe insulin resistance. We recently conducted a 24 week, multicenter, single-arm trial (EMPIRE-01) that demonstrated a certain level of effectiveness and safety of empagliflozin for these conditions. To evaluate treatment safety over a longer period, we have now performed an additional 28 week trial (EMPIRE-02) that followed on from EMPIRE-01.
The primary and secondary outcomes were safety and efficacy evaluations, respectively. All eight subjects of the EMPIRE-01 trial participated in EMPIRE-02.
Twenty adverse events (AEs) were recorded among five individuals during the combined 52 week treatment period of both trials. Whereas one case of chronic hepatitis B was moderate in severity, all other AEs were mild. There were thus no serious AEs or events necessitating discontinuation or suspension of treatment or a reduction in drug dose. Whereas ketoacidosis or marked increases in serum ketone body levels were not observed, the mean body mass of the subjects was decreased slightly after completion of EMPIRE-02. The improvement in mean values of glycemic parameters observed in EMPIRE-01 was not sustained in EMPIRE-02, mostly because of one individual whose parameters deteriorated markedly, likely as a result of nonadherence to diet therapy. The improvement in glycemic parameters was sustained during EMPIRE-02 after exclusion of this subject from analysis.
Empagliflozin demonstrated a certain level of safety and efficacy for the treatment of insulin resistance syndrome and lipoatrophic diabetes over 52 weeks, confirming its potential as a therapeutic option.
目的/引言：胰岛素抵抗综合征和脂肪萎缩性糖尿病是罕见的疾病，其特征是发展为严重胰岛素抵抗的难治性糖尿病。我们最近进行了一项为期 24 周、多中心、单臂试验（EMPIRE-01），证明恩格列净对这些疾病具有一定的疗效和安全性。为了评估更长时间的治疗安全性，我们现在进行了一项额外的 28 周试验（EMPIRE-02），该试验是在 EMPIRE-01 之后进行的。
主要和次要结局分别为安全性和疗效评估。EMPIRE-01 试验的所有 8 名受试者均参加了 EMPIRE-02 试验。
在两项试验的联合 52 周治疗期间，有 5 名个体共记录到 20 例不良事件（AE）。虽然一例慢性乙型肝炎为中度严重，但所有其他 AE 均为轻度。因此，没有严重的 AE 或需要停药、暂停治疗或减少药物剂量的事件。虽然未观察到酮症酸中毒或血清酮体水平显著升高，但 EMPIRE-02 完成后，受试者的平均体重略有下降。在 EMPIRE-01 中观察到的血糖参数平均值的改善在 EMPIRE-02 中并未持续，这主要是由于一名个体的参数明显恶化，可能是由于饮食疗法不依从所致。在排除该个体后，血糖参数的改善在 EMPIRE-02 期间仍持续。
恩格列净在 52 周内治疗胰岛素抵抗综合征和脂肪萎缩性糖尿病显示出一定的安全性和疗效，证实了其作为一种治疗选择的潜力。
