Fixed dose combination of dapagliflozin, glimepiride and extended-release metformin tablets in patients with type 2 diabetes poorly controlled by metformin and glimepiride: A phase III, open label, randomized clinical study in India

IF 5.7 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes, Obesity & Metabolism Pub Date : 2025-02-14 DOI:10.1111/dom.16218

Rakesh Sahay DM (Endocrinology), Dinesh Gangwani MD (Medicine), Manish Singh MD (Medicine), Sandeep Gupta MD (Medicine), Narendra Kale DNB (General Medicine), Manoj Srivastava MD (Medicine), Prakash Kurmi MD (Medicine), Jayesh Ambaliya MD (General Medicine), Nilesh Lomte DM (Endocrinology), Sandip Gofne MD (Medicine), Saurabh Agarwal MD (Medicine), Priyanka Kashid MBBS, Vikas Agarwal DM (Cardiology), Pradeep Rai MD (General Medicine), Surendra Sharma DM (Endocrinology), L. Sreenivasa Murthy MD (General Medicine), Mandodari Rajurkar MPH, Shruti Saha DM (Pharmacology), Piyush Patel MD (Pharmacology), Dipak Patil MD (Pharmacology), Pravin Ghadge MD (Pharmacology), Lalit Lakhwani MD (Pharmacology), Suyog Mehta MD (Pharmacology), Sadhna J. Joglekar MD (Pharmacology)

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Abstract

Aim

To evaluate the efficacy and safety of a triple fixed-dose combination (FDC) therapy of dapagliflozin + glimepiride + metformin hydrochloride extended-release (DAPA + GLIM + MET ER) tablets in Indian patients with type 2 diabetes mellitus (T2DM) inadequately controlled by combination of GLIM + MET.

Materials and Methods

A phase III, randomized, open-label, active-controlled study was conducted for a maximum 30 weeks (primary treatment [16 weeks]; uptitration [12 weeks] and follow-up [2 weeks]). Eligible patients were randomized in a 1:1 ratio to receive either the FDC of DAPA + GLIM + MET ER or the FDC of GLIM + MET prolonged-release (PR) once-daily. The primary efficacy endpoint was a change in glycated haemoglobin (HbA1c) from baseline to week 16.

Results

The mean reduction in HbA1c from baseline to week 16 was significantly greater with the FDC of DAPA + GLIM + MET ER compared to the FDC of GLIM + MET PR (−1.98% ± 1.01% vs. −1.64% ± 0.86%, p = 0.0047). The mean reduction in HbA1c from baseline to week 12 was significantly greater with the FDC of DAPA + GLIM + MET ER versus dual FDC (p < 0.0001). The proportion of patients achieving HbA1c <7.0% was significantly greater with the FDC of DAPA + GLIM + MET ER versus dual FDC at week 12 (19.1% vs. 6.5%; p = 0.0002) and week 16 (52.6% vs. 36.7%; p = 0.0015). A significant decrease in HbA1c, fasting and post-prandial blood glucose from baseline to weeks 12, 16, and 28 was observed in both arms. The incidence of TEAEs was similar across both arms.

Conclusion

This study demonstrated that the FDC of DAPA + GLIM + MET ER tablets once daily was significantly better than dual FDC in achieving glycaemic control in patients with poorly controlled T2DM. Both treatments were well-tolerated.

Trial Registration

CTRI/2022/03/041424, registered on 28 March 2022.

Abstract Image

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固定剂量联合达格列净、格列美脲和二甲双胍缓释片治疗二甲双胍和格列美脲控制不良的2型糖尿病患者：一项在印度进行的开放标签随机III期临床研究

目的：评估达帕格列净+格列美脲+盐酸二甲双胍缓释片（DAPA + GLIM + MET ER）三联固定剂量复方（FDC）疗法对格列美脲+盐酸二甲双胍联合用药控制不佳的印度 2 型糖尿病（T2DM）患者的疗效和安全性：进行了一项为期最长 30 周的 III 期随机、开放标签、主动对照研究（初始治疗 [16 周]；升级治疗 [12 周] 和随访 [2 周]）。符合条件的患者按 1:1 的比例随机接受每日一次的 DAPA + GLIM + MET ER FDC 或 GLIM + MET 长效缓释 (PR) FDC。主要疗效终点是糖化血红蛋白（HbA1c）从基线到第16周的变化：与 GLIM + MET PR FDC 相比，DAPA + GLIM + MET ER FDC 从基线到第 16 周的 HbA1c 平均降幅明显更大（-1.98% ± 1.01% vs. -1.64% ± 0.86%，p = 0.0047）。从基线到第 12 周，DAPA + GLIM + MET ER FDC 的 HbA1c 平均降幅显著高于双 FDC（p 结论：DAPA + GLIM + MET ER FDC 的 HbA1c 平均降幅显著高于双 FDC：这项研究表明，在实现对控制不佳的 T2DM 患者的血糖控制方面，每日一次的 DAPA + GLIM + MET ER 片剂 FDC 明显优于双 FDC。两种疗法的耐受性均良好：试验注册：CTRI/2022/03/041424，注册日期：2022年3月28日。

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来源期刊

Diabetes, Obesity & Metabolism 医学-内分泌学与代谢

CiteScore

10.90

自引率

6.90%

发文量

319

审稿时长

3-8 weeks

期刊介绍： Diabetes, Obesity and Metabolism is primarily a journal of clinical and experimental pharmacology and therapeutics covering the interrelated areas of diabetes, obesity and metabolism. The journal prioritises high-quality original research that reports on the effects of new or existing therapies, including dietary, exercise and lifestyle (non-pharmacological) interventions, in any aspect of metabolic and endocrine disease, either in humans or animal and cellular systems. ‘Metabolism’ may relate to lipids, bone and drug metabolism, or broader aspects of endocrine dysfunction. Preclinical pharmacology, pharmacokinetic studies, meta-analyses and those addressing drug safety and tolerability are also highly suitable for publication in this journal. Original research may be published as a main paper or as a research letter.