Effectiveness of semaglutide on survival outcomes in patients with type 2 diabetes and chronic kidney disease.
This multicentre retrospective observational study used TriNetX, a global healthcare data platform, to examine real-world associations between semaglutide use and survival outcomes in adults with type 2 diabetes (T2D) and chronic kidney disease (CKD). Researchers identified over 1.1 million eligible patients, of whom 14,511 initiated semaglutide and 69,700 initiated sitagliptin between 2018 and 2020. After propensity score matching to balance baseline characteristics, 13,703 patients were included in each group. The study found that the semaglutide group had a significantly lower 3-year incidence of all-cause death (7.2% vs. 9.5%) compared with the sitagliptin group. Secondary outcomes including acute heart failure, acute myocardial infarction, and stroke also favored semaglutide. The authors note these findings are consistent with the randomized FLOW trial. Key limitations include the retrospective, non-randomized design, potential for residual confounding despite propensity score matching, reliance on administrative coding data, and the inability to account for medication adherence or dosing details. Findings should be interpreted as associative, not causal.
Why this grade: Large propensity-score-matched real-world cohort (n=13,703 per group) in humans provides moderate evidence, but the retrospective observational design precludes causal inference due to residual confounding.
Background Type 2 diabetes (T2D) and chronic kidney disease (CKD) significantly increase the risk of cardiovascular events, including death and heart failure (HF). The FLOW trial demonstrated that semaglutide reduces all-cause death, cardiovascular events and HF risk in patients with T2D and CKD. Since there is a difference in patient characteristics between clinical trials and real-world data, this study aims to investigate the association of semaglutide and all-cause death, acute HF or cardiovascular outcomes in patients with T2D and CKD using the data platform. Methods This multicentre retrospective observational study using TriNetX, a global healthcare data platform. We identified 1 151 750 patients aged ≥18 years with T2D and CKD diagnosed before 31 December 2020. Among these, 14 511 patients initiated semaglutide and 69 700 initiated sitagliptin between 1 January 2018 and 31 December 2020. After propensity score matching, 13 703 patients were included in each group. The primary outcome was the 3-year incidence of all-cause death. Secondary outcomes included acute HF, acute myocardial infarction and stroke. Results The 3-year risk of all-cause death in the semaglutide group relative to the sitagliptin group was significantly lower (7.2% (943/13 703) vs 9.5% (1196/13 703); p Conclusions In patients with T2D and CKD, semaglutide was associated with a lower 3-year risk of all-cause death compared with sitagliptin.
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