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Efficacy and Safety of Pharmacological Combination Therapies for the Treatment of Type 2 Diabetes in China: A Systematic Review and Meta-Analysis

57 Pages Posted: 10 May 2019

See all articles by Shuyan Gu

Shuyan Gu

Zhejiang University - Centre for Health Policy Studies; Nanjing University - Center for Health Policy and Management Studies

Xueshan Sun

Zhejiang University - Centre for Health Policy Studies

Xiaoqian Hu

Zhejiang University - Centre for Health Policy Studies

Yuxuan Gu

Zhejiang University - Centre for Health Policy Studies

Jingming Wei

Kaiser Permanente - Center for Health Policy Studies

Qilong Gao

Kaiser Permanente - Center for Health Policy Studies

Can Zhao

Kaiser Permanente - Center for Health Policy Studies

Lizheng Shi

Tulane University - School of Public Health and Tropical Medicine

Hengjin Dong

Zhejiang University - Centre for Health Policy Studies

More...

Abstract

Background: Chinese guideline recommends using combination therapy of antidiabetic-drug plus metformin for type 2 diabetes (T2DM) patients failed to control glucose on metformin. Treatment effect varies between antidiabetic drugs, but there is no direct evidence on comparing the effect of each alternative drug plus metformin. This study aims to estimate and compare the efficacy and safety of seven classes of antidiabetic-drug added onto metformin for Chinese T2DM patients failed on metformin.

Methods: Systematic review was performed by searching databases including CNKI, WanFang, CQVIP, PubMed, EMBASE, Web-of-Science, ScienceDirect, Cochrane-Library, to identify randomized controlled trials(1990-2016) comparing the treatment effect of 'antidiabetic-drug + metformin vs metformin' or 'metformin vs placebo/lifestyle-intervention' in Chinese T2DM patients. Based on Chinese guideline, three-line eight-class of antidiabetic-drugs were included: 1st-line-drug(metformin), 2nd-line-drug/oral-drug(α-glycosidase inhibitor, sulfonylurea, glinide, DPP-4 inhibitor, thiazolidinedione), 3rd-line-drug/injectable-drug(insulin, GLP-1 receptor agonist). Using metformin as common comparator, meta-analyses and indirect-treatment-comparisons were used to estimate the effect of 'antidiabetic-drug + metformin vs placebo/lifestyle-intervention'.

Findings: 325 studies were finally included. Overall, compared with placebo/lifestyle-intervention, 'oral-drug + metformin' and 'injectable-drug + metformin' reduced HbA1c level by 1·89% and 2·28%, BMI level by 2·55kg/m2 and 3·10kg/m2, TC level by 1·03mmol/l and 1·50mmol/l, SBP level by 5·59mmHg and 8·51mmHg, while increased HDL-C level by 0·31mmol/l and 0·18mmol/l, respectively. In 'oral-drug + metformin', the top two treatments for reducing HbA1c level were 'glinide + metformin' (WMD:-2·03,95%CI[-2·70,-1·36]) and 'sulfonylurea + metformin' (WMD:-2·00,95%CI[-2·64,-1·36]); for reducing BMI level were 'glinide + metformin' (WMD:-4·25,95%CI[-5·70,-2·80]) and 'DPP-4 inhibitor + metformin' (WMD:-2·81,95%CI[-4·22,-1·40]); for reducing TC level were 'α-glycosidase inhibitor + metformin'(WMD:-1·41,95%CI[-2·15,-0·68]) and 'DPP-4 inhibitor + metformin' (WMD:-1·22,95%CI[-1·71,-0·73]); for increasing HDL-C level were 'α-glycosidase inhibitor + metformin'(WMD:0·51,95%CI[0·27,0·75]) and 'thiazolidinedione + metformin' (WMD:0·35,95%CI[0·10,0·60]). In 'injectable-drug + metformin', 'GLP-1 receptor agonist + metformin' was superior to 'insulin + metformin' in reducing HbA1c level (WMD:-2·42vs-2·04) and BMI level (WMD:-3·27vs-2·05), while inferior to 'insulin + metformin' in reducing TC level (WMD:-1·43vs-1·79). All combination therapies had no significant difference on risks of hypoglycemia or gastrointestinal-reaction vs placebo/lifestyle-intervention.

Interpretation: Pharmacological combination therapies had better efficacy than placebo/lifestyle-intervention in Chinese T2DM patients.

Funding: No funding was received.

Declaration of Interest: There are no relevant conflicts of interest to disclose.

Suggested Citation

Gu, Shuyan and Sun, Xueshan and Hu, Xiaoqian and Gu, Yuxuan and Wei, Jingming and Gao, Qilong and Zhao, Can and Shi, Lizheng and Dong, Hengjin, Efficacy and Safety of Pharmacological Combination Therapies for the Treatment of Type 2 Diabetes in China: A Systematic Review and Meta-Analysis (August 5, 2019). Available at SSRN: https://ssrn.com/abstract=3384901 or http://dx.doi.org/10.2139/ssrn.3384901

Shuyan Gu

Zhejiang University - Centre for Health Policy Studies

China

Nanjing University - Center for Health Policy and Management Studies ( email )

Nanjing
China

Xueshan Sun

Zhejiang University - Centre for Health Policy Studies

China

Xiaoqian Hu

Zhejiang University - Centre for Health Policy Studies

China

Yuxuan Gu

Zhejiang University - Centre for Health Policy Studies

China

Jingming Wei

Kaiser Permanente - Center for Health Policy Studies

650 Charles Young Drive South
A2-125 CHS, Box 956900
Los Angeles, CA 90095-6900
United States

Qilong Gao

Kaiser Permanente - Center for Health Policy Studies

650 Charles Young Drive South
A2-125 CHS, Box 956900
Los Angeles, CA 90095-6900
United States

Can Zhao

Kaiser Permanente - Center for Health Policy Studies

650 Charles Young Drive South
A2-125 CHS, Box 956900
Los Angeles, CA 90095-6900
United States

Lizheng Shi

Tulane University - School of Public Health and Tropical Medicine

New Orleans, LA 70112
United States

Hengjin Dong (Contact Author)

Zhejiang University - Centre for Health Policy Studies ( email )

China