OBJECTIVES : Chinese clinical guideline recommends using combination therapy of an antidiabetic drug plus metformin for type 2 diabetes (T2DM) patients failed to control glucose by metformin. There are multiple antidiabetic drugs in China, which vary in efficacy and safety. However, no study exists comparing each alternative drug plus metformin at the same time. This study aims to estimate and compare the efficacy of alternative classes of antidiabetic drug plus metformin for Chinese T2DM patients.

METHODS : Systematic literature review was conducted by searching databases including CNKI, WanFang, CQVIP, PubMed, EMBASE, Web-of-Science, ScienceDirect, Cochrane-Library, to identify randomized controlled trials (1990-2016) comparing the efficacy of antidiabetic-drug+metformin vs. metformin, or metformin vs. placebo/lifestyle-intervention (i.e., diet/exercise) in Chinese T2DM patients. Referring to Chinese guideline, three-lines eight-classes of antidiabetic drugs were included: 1^st-line-drug (metformin), 2^nd-line-drug/oral-drug (α-glycosidase-inhibitor, sulfonylurea, glinide, DPP-4-inhibitor, thiazolidinedione), 3^rd-line-drug/injectable-drug (insulin, GLP-1-receptor-agonist). Meta-analysis was used to estimate the efficacy of antidiabetic-drug+metformin vs. metformin, or metformin vs. placebo/lifestyle-intervention. Then using metformin as common comparator, indirect-treatment-comparison was used to estimate the efficacy of antidiabetic-drug+metformin vs. placebo/lifestyle-intervention.

RESULTS : 99,072 records were identified through database search, and 325 studies were included. Compared with placebo/lifestyle-intervention, oral-drug+metformin could decrease HbA1c by 1.79~2.03%, BMI by 1.64~4.25kg/m², TC by 0.66~1.41mmol/l, SBP by 4.13~6.67mmHg, while increase HDL-C by 0.09~0.51mmol/l, hypoglycemia by 0~5%; injectable-drug+metformin could decrease HbA1c by 2.04~2.42%, BMI by 2.05~3.27kg/m², TC by 1.43~1.79mmol/l, SBP by 8.51mmHg, hypoglycemia by 1%, while increase HDL-C by 0.18 mmol/l. In the five oral-drug+metformin, glinide+metformin was optimal for decreasing HbA1c and BMI, α-glycosidase-inhibitor+metformin was optimal for decreasing TC and increasing HDL-C, DPP-4-inhibitor+metformin was optimal for decreasing SBP. In the two injectable-drug+metformin, GLP-1-receptor-agonist+metformin was optimal for decreasing HbA1c and BMI, insulin+metformin was optimal for decreasing TC, while no data supported for comparison in HDL-C and SBP.

CONCLUSIONS : This study shows that pharmacological combination therapies have better efficacy than placebo/lifestyle-intervention in Chinese T2DM patients.