Comparison Between Pioglitazone/Metformin Combination Therapy and Sitagliptin/Metformin Combination Therapy on the Efficacy in Chinese Type 2 Diabetic Adults Insufficiently Controlled with Metformin: Study Protocol of an Open-Label, Multicenter, Non-Inferiority Parallel-Group Randomized Controlled Trial

Fang Zhang; Lizhi Tang; Jing Li; Zhe Yan; Juan Li; Nanwei Tong

doi:10.2147/DMSO.S293307

Comparison Between Pioglitazone/Metformin Combination Therapy and Sitagliptin/Metformin Combination Therapy on the Efficacy in Chinese Type 2 Diabetic Adults Insufficiently Controlled with Metformin: Study Protocol of an Open-Label, Multicenter, Non-Inferiority Parallel-Group Randomized Controlled Trial

Diabetes Metab Syndr Obes. 2021 Mar 18:14:1243-1252. doi: 10.2147/DMSO.S293307. eCollection 2021.

Authors

Fang Zhang¹, Lizhi Tang¹, Jing Li¹, Zhe Yan¹, Juan Li¹, Nanwei Tong¹

Affiliation

¹ Division of Endocrinology and Metabolism, West China Hospital of Sichuan University, Chengdu, People's Republic of China.

Abstract

Introduction: The prevalence of type 2 diabetes (T2D) has risen substantially in China, where its pathophysiology is primarily characterized by insulin resistance (IR). Alleviating IR may help with the management of T2D in the Chinese population. Pioglitazone and sitagliptin are two hypoglycemic medications with different pharmacological actions, both of which are optimal choices for use in combination with metformin. Previous studies have yielded mixed findings regarding the differences in hypoglycemic effects between the two agents. Though pioglitazone is associated with weight gain, both drugs have been shown to decrease visceral adipose tissue (VAT) and improve IR in individuals with T2D. There is a lack of direct comparisons between pioglitazone and sitagliptin among Chinese individuals with T2D. Therefore, this paper describes a protocol for a randomized controlled trial (RCT) that investigates the differences in hypoglycemic efficacy, IR improvement, and safety profiles between these drugs.

Methods and analysis: This is a 24-week, open-label, multicenter, non-inferiority parallel-group RCT with a 1:1 allocation ratio. It compares pioglitazone/metformin (15 mg/500 mg) combination therapy with sitagliptin/metformin (50 mg/500 mg) combination therapy in Chinese adults with T2D insufficiently controlled with metformin. The primary outcomes are HbA1c reduction, insulin level increase, and IR index change. The secondary outcomes are body weight and abdominal VAT decreases, lipid profiles, and inflammatory indicators. Tolerability and safety data will also be collected.

Conclusion: It is believed that the direct comparisons of the hypoglycemic effects, VAT reductions, and safety profiles between pioglitazone and sitagliptin will help to optimize treatments for Chinese adults with T2D who are primarily characterized by IR.

Trial registration number: Chinese Clinical Trial Registry (ChiCTR1900021861).

Keywords: combination therapy; pioglitazone; randomized controlled trial; sitagliptin; study protocol; type 2 diabetes.

Grants and funding

This trial is funded by the Hangzhou Zhongmei Huadong Pharmaceutical Co., Ltd and the 1-3-5 Project for Disciplines of Excellence in West China Hospital of Sichuan University. This work is also funded by Sichuan Provincial Science and Technology Foundation (Grant number 2021YJ0441). The funding bodies have not and will not participate in the study design, the collection, management, analysis or interpretation of data, nor writing the findings for publication.