All-cause mortality and cardiovascular outcomes with sodium-glucose Co-transporter 2 inhibitors, glucagon-like peptide-1 receptor agonists and with combination therapy in people with type 2 diabetes.

AIM: To assess the relationship of sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor analogues (GLP-1RA) and their combination (SGLT2i + GLP-1RA) with 5-year risk of all-cause mortality, hospitalization and cardiovascular/macrovascular disease in people with type 2 diabetes. MATERIALS AND METHODS: Retrospective cohort analysis of 2.2 million people with type 2 diabetes receiving insulin across 85 health care organizations using a global federated health research network. Three intervention cohorts (SGLT2i, GLP-1RA and SGLT2i + GLP-1RA) were compared against a control cohort (no SGLT2i/GLP-1RA). Propensity score matching for age, ischaemic heart disease, sex, hypertension, chronic kidney disease, heart failure and glycated haemoglobin was used to balance cohorts 1:1 (SGLT2i, n = 143 600; GLP-1RA, n = 186 841; SGLT-2i + GLP-1RA, n = 108 504). A sub-analysis comparing combination and monotherapy cohorts was also performed. RESULTS: The intervention cohorts showed a reduced hazard ratio (HR, 95% confidence interval) over 5 years compared with the control cohort for all-cause mortality (SGLT2i 0.49, 0.48-0.50; GLP-1RA 0.47, 0.46-0.48; combination 0.25, 0.24-0.26), hospitalization (0.73, 0.72-0.74; 0.69, 0.68-0.69; 0.60, 0.59-0.61) and acute myocardial infarct (0.75, 0.72-0.78; 0.70, 0.68-0.73; 0.63, 0.60-0.66), respectively. All other outcomes showed a significant risk reduction in favour of the intervention cohorts. The sub-analysis showed a significant risk reduction in all-cause mortality for combination therapy versus SGLT2i (0.53, 0.50-0.55) and GLP-1RA (0.56, 0.54-0.59). CONCLUSIONS: SGLT2i, GLP-1RAs or combination therapy confers mortality and cardiovascular protection in people with type 2 diabetes over 5 years. Combination therapy was associated with the greatest risk reduction in all-cause mortality versus a propensity matched control cohort. In addition, combination therapy offers a reduction in 5-year all-cause mortality when compared directly against either monotherapy.

Federated Electronic Health Record Database via a Public-Private Partnership to Enhance Health Care Equity by Disparity Discovery and Equitable Clinical Trial Recruitment.

Despite increasingly stringent requirements from regulatory agencies, clinical trials often fail to recruit study populations representative of real-world demographics and disease prevalence and are often skewed away from racial/ethnic minorities. Consequently, data produced by such trials can result in treatment guidelines and outcome expectations that do not apply to racial/ethnic minorities, further widening health disparities. In this study, we describe a new tool, the TriNetX Diversity Lens ("Diversity Lens"), which augments the existing electronic health record querying functionality of TriNetX and allows clinical trial sponsors to rapidly evaluate the potential impact of inclusion and exclusion criteria on the eligibility rates of different racial and ethnic groups. We describe the development of Diversity Lens in collaboration with public and private stakeholders. Additionally, we feature examples of how Diversity Lens can bring to the surface insights into existing health disparities and prospectively explore the impact of study criteria on the eligibility of racial/ethnic minorities.