1 INTRODUCTION

Whereas the immediate-release (IR) formulation of metformin has to be taken two or three times a day, the extended-release (XR) formulation enables once-daily administration and so might help to improve patient adherence, particularly in patients with polypharmacy.

Several studies have assessed metformin XR's efficacy, safety, and pharmacokinetics (PK) in healthy people and those with type 2 diabetes (T2D).^1-4 Many factors affect metformin absorption, disposition and elimination in patients with chronic kidney disease (CKD), leading to metformin accumulation. Although dose adjustment has been simulated using data from metformin XR-treated patients with various levels of kidney function,⁵ the pharmacodynamics (PD) and PK of metformin XR in patients with T2D and a defined CKD stage have not previously been studied. We therefore decided to comprehensively assess the efficacy, steady-state PK, and safety of three dose levels of metformin XR in people with T2D and CKD stage 3B.

中文翻译：

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缓释二甲双胍在 2 型糖尿病和慢性肾病 3B 期患者中的药效学和药代动力学

1 简介

虽然二甲双胍的速释 (IR) 制剂必须每天服用两到三次，但缓释 (XR) 制剂可以每天服用一次，因此可能有助于提高患者的依从性，尤其是在服用多种药物的患者中。

几项研究评估了二甲双胍 XR 在健康人和 2 型糖尿病 (T2D) 患者中的疗效、安全性和药代动力学 (PK)。^1-4许多因素影响慢性肾脏病 (CKD) 患者的二甲双胍吸收、处置和消除，导致二甲双胍蓄积。尽管使用二甲双胍 XR 治疗的具有不同肾功能水平的患者的数据模拟了剂量调整⁵，但之前尚未研究过二甲双胍 XR 在 T2D 和明确的 CKD 分期患者中的药效学 (PD) 和 PK。因此，我们决定全面评估三个剂量水平的二甲双胍 XR 在 T2D 和 CKD 3B 期患者中的疗效、稳态 PK 和安全性。