External Control Arm With Real World Data to Assess the Effect of Semaglutide on Chronic Kidney Disease Risk Among Patients With Type 2 Diabetes
Author(s)
Onur Baser, MS, PhD1, Nehir Yapar, MS2, Katarzyna Rodchenko, MA, MPH2, Munira Mohamed, MPH3, Alexandra Passarelli, MPH2, Shuangrui Chen, MS2, Yuanqing Lu, MS3.
1City University of New York, New York, NY, USA, 2Columbia Data Analytics, New York, NY, USA, 3Columbia Data Analytics, Ann Arbor, MI, USA.
1City University of New York, New York, NY, USA, 2Columbia Data Analytics, New York, NY, USA, 3Columbia Data Analytics, Ann Arbor, MI, USA.
OBJECTIVES: Patients with type-2 diabetes and chronic kidney disease confront substantial health risks, particularly kidney failure, cardiovascular events, and premature death. Clinical trials have demonstrated the efficacy of semaglutide in mitigating these risks, showing promise in slowing kidney disease progression and reducing cardiovascular-related morbidity and mortality. However, the real-world effectiveness and long-term outcomes related to the treatment are not fully established. An external control arm was created for the FLOW Clinical Trial (FLOW ClinicalTrials.gov number:NCT03819153).
METHODS: Using Kythera Labs data from JUN2019-JUN2024, an external control arm was created based on the inclusion and exclusion criteria identified under the FLOW clinical trial. Primary outcomes were major kidney disease events—a composite of kidney failure onset (dialysis, transplantation, or estimated glomerular filtration rate [eGFR] <15 ml/min per 1.73 m2), and at least 50% reduction in eGFR from the baseline). Propensity score matching and Cox regression were used to determine risk-adjusted outcomes.
RESULTS: The control arm cohort included 896,257 patients; the clinical trial cohort included 1,766 patients. Age, sex, socioeconomic status, and comorbidities including cardiovascular disease, anemia, depression, and mineral and bone disorder significantly affected the likelihood of a primary event. After controlling for these factors, primary event risk was 26% lower in the external control arm semaglutide group than in the control group (702 vs 1,068 patients; hazard ratio: 0.74; 95% confidence interval: 0.67, 0.81) vs 24% in the clinical trial semaglutide group.
CONCLUSIONS: Semaglutide treatment demonstrated a significant reduction in the risk of clinically relevant renal outcomes in a real-world external arm study. Characterized by its expansive sample size, this analysis encompassed a cohort >500 times larger than that of the corresponding clinical trial, the substantial scale of this real-world evidence provides robust support for the renoprotective effects of semaglutide, reinforcing its potential as a valuable therapeutic option in managing kidney-related complications.
METHODS: Using Kythera Labs data from JUN2019-JUN2024, an external control arm was created based on the inclusion and exclusion criteria identified under the FLOW clinical trial. Primary outcomes were major kidney disease events—a composite of kidney failure onset (dialysis, transplantation, or estimated glomerular filtration rate [eGFR] <15 ml/min per 1.73 m2), and at least 50% reduction in eGFR from the baseline). Propensity score matching and Cox regression were used to determine risk-adjusted outcomes.
RESULTS: The control arm cohort included 896,257 patients; the clinical trial cohort included 1,766 patients. Age, sex, socioeconomic status, and comorbidities including cardiovascular disease, anemia, depression, and mineral and bone disorder significantly affected the likelihood of a primary event. After controlling for these factors, primary event risk was 26% lower in the external control arm semaglutide group than in the control group (702 vs 1,068 patients; hazard ratio: 0.74; 95% confidence interval: 0.67, 0.81) vs 24% in the clinical trial semaglutide group.
CONCLUSIONS: Semaglutide treatment demonstrated a significant reduction in the risk of clinically relevant renal outcomes in a real-world external arm study. Characterized by its expansive sample size, this analysis encompassed a cohort >500 times larger than that of the corresponding clinical trial, the substantial scale of this real-world evidence provides robust support for the renoprotective effects of semaglutide, reinforcing its potential as a valuable therapeutic option in managing kidney-related complications.
Conference/Value in Health Info
2025-05, ISPOR 2025, Montréal, Quebec, CA
Value in Health, Volume 28, Issue S1
Code
CO77
Topic
Clinical Outcomes
Topic Subcategory
Clinical Outcomes Assessment
Disease
SDC: Diabetes/Endocrine/Metabolic Disorders (including obesity), SDC: Urinary/Kidney Disorders