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

Abstract

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 criteriadRCTs with at least 50 patients in each arm, >70% of population from Asian or white group, duration ‡24 weeks, and publication up to March 2019dwere selected for systematic review and metaanalysis. DATA EXTRACTION Data extraction was done for aggregated study-level data by two independent researchers. Absolute changes in HbA 1c (%) from baseline to 24 weeks between the drug and placebo were considered as the primary end point of the study. DATA SYNTHESIS Change in HbA 1c 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.

Effect of canagliflozin on N-terminal pro-brain natriuretic peptide in patients with type 2 diabetes and chronic heart failure according to baseline use of glucose-lowering agents

“…This may partially explain the lower rate of baseline metformin use and higher rate of baseline DPP-4 inhibitor use in the clinically stable cohort of the CANDLE trial. Given their safety and efficacy for glycemic control, DPP-4 inhibitors are still prescribed frequently in Asian populations with T2D, even in patients with HF [ 41 – 43 ]. The present study showed that the baseline use of DPP-4 inhibitors did not influence the effects of canagliflozin treatment on the clinical variables examined.…”

Incidence and pathophysiology of diabetes in South Asian adults living in India and Pakistan compared with US blacks and whites

“…This has major implications for ethnicity-specific diabetes treatment guidelines. 33 Our study has several limitations that should be taken into account in interpreting these results. Although both CARRS and ARIC were population-based cohorts, they were assembled at different time period using different sampling methodologies, and also CARRS was purely urban, while ARIC was largely urban and suburban.…”

Glycemic Variability Impacted by SGLT2 Inhibitors and GLP 1 Agonists in Patients with Diabetes Mellitus: A Systematic Review and Meta-Analysis

“…Our study failed to find differences between monotherapy and add-on therapy with SGLT-2 inhibitors or GLP-1 agonists for reducing MAGE and MBG levels in patients with diabetes. SGLT-2 inhibitors and GLP-1 agonists have the ability to improve cardiovascular outcomes and/or renal outcomes [ 1 , 7 , 8 , 9 , 38 ]; however, more studies are required to evaluate their various effects, including those on GV.…”