Efficacy of Modern Diabetes Treatments DPP-4i, SGLT-2i, and GLP-1RA in White and Asian Patients With Diabetes: A Systematic Review and Meta-analysis of Randomized Controlled Trials

BACKGROUND The pathophysiology of type 2 diabetes differs markedly by ethnicity. PURPOSE A systematic review and meta-analysis was conducted to assess the impact of ethnicity on the glucose-lowering efficacy of the newer oral agents, sodium–glucose cotransporter 2 inhibitors (SGLT-2i), glucagon-like peptide 1 receptor agonists (GLP-1RA), and dipeptidyl peptidase 4 inhibitors (DPP-4i), using evidence from randomized clinical trials (RCTs). DATA SOURCES A literature search was conducted in PubMed of all randomized, placebo-controlled trials of DPP-4i, SGLT-2i, and GLP-1RA. The search strategy was developed based on Medical Subject Headings (MeSH) terms and keywords. STUDY SELECTION A total of 64 studies that qualified for meta-analysis after full-text review based on predefined inclusion and exclusion criteria—RCTs with at least 50 patients in each arm, >70% of population from Asian or white group, duration ≥24 weeks, and publication up to March 2019—were selected for systematic review and meta-analysis. DATA EXTRACTION Data extraction was done for aggregated study-level data by two independent researchers. Absolute changes in HbA1c (%) from baseline to 24 weeks between the drug and placebo were considered as the primary end point of the study. DATA SYNTHESIS Change in HbA1c was evaluated by computing mean differences and 95% CIs between treatment and placebo arms. LIMITATIONS The study is based on summarized data and could not be separated based on East Asians and South Asians. CONCLUSIONS The glucose-lowering efficacy of SGLT-2i, and to a lesser extent DPP-4i, was greater in studies of predominantly Asian ethnicity compared with studies of predominantly white ethnicity. There was no difference seen by ethnicity for GLP-1RA.