{"doi":"10.2337/dc22-0772","title":"Cardiovascular and Renal Benefits of Novel Diabetes Drugs by Baseline Cardiovascular Risk: A Systematic Review, Meta-analysis, and Meta-regression","abstract":"BACKGROUND: Eligibility for glucagon-like peptide 1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) has been expanded to patients with diabetes at lower cardiovascular risk, but whether treatment benefits differ by risk levels is not clear. PURPOSE: To investigate whether patients with varying risks differ in cardiovascular and renal benefits from GLP-1RA and SGLT2i with use of meta-analysis and meta-regression. DATA SOURCES: We performed a systematic review using PubMed through 7 November 2022. STUDY SELECTION: We included reports of GLP-1RA and SGLT2i confirmatory randomized trials in adult patients with safety or efficacy end point data. DATA EXTRACTION: Hazard ratio (HR) and event rate data were extracted for mortality, cardiovascular, and renal outcomes. DATA SYNTHESIS: We analyzed 9 GLP-1RA and 13 SGLT2i trials comprising 154,649 patients. Summary HRs were significant for cardiovascular mortality (GLP-1RA 0.87 and SGLT2i 0.86), major adverse cardiovascular events (0.87 and 0.88), heart failure (0.89 and 0.70), and renal (0.84 and 0.65) outcomes. For stroke, efficacy was significant for GLP-1RA (0.84) but not for SGLT2i (0.92). Associations between control arm cardiovascular mortality rates and HRs were nonsignificant. Five-year absolute risk reductions (0.80-4.25%) increased to 11.6% for heart failure in SGLT2i trials in patients with high risk (Pslope < 0.001). For GLP1-RAs, associations were nonsignificant. LIMITATIONS: Analyses were limited by lack of patient-level data, consistency in end point definitions, and variation in cardiovascular mortality rates for GLP-1RA trials. CONCLUSIONS: Relative effects of novel diabetes drugs are preserved across baseline cardiovascular risk, whereas absolute benefits increase at higher risks, particularly regarding heart failure. Our findings suggest a need for baseline risk assessment tools to identify variation in absolute treatment benefits and improve decision-making.","journal":"Diabetes Care","year":2023,"id":321422,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":44,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9604,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":972291,"name":"Malak Tahsin","orcid":"0000-0001-6299-6673","position":1,"is_corresponding":false},{"id":902788,"name":"Kirsten E. Fleischmann","orcid":"0000-0002-3813-4384","position":2,"is_corresponding":false},{"id":29200,"name":"Umesh Masharani","orcid":"0000-0002-3269-804X","position":3,"is_corresponding":false},{"id":706211,"name":"Joseph Yeboah","orcid":"0000-0001-6274-5882","position":4,"is_corresponding":false},{"id":1033502,"name":"Meyeon Park","orcid":"0000-0002-2695-0894","position":5,"is_corresponding":false},{"id":824231,"name":"Lihua Li","orcid":"0000-0003-3154-9576","position":6,"is_corresponding":false},{"id":1003714,"name":"Ellerie Weber","orcid":"0000-0003-3179-7035","position":7,"is_corresponding":false},{"id":411095,"name":"Yan Li","orcid":"0000-0001-6155-0389","position":8,"is_corresponding":false},{"id":720502,"name":"Asem Berkalieva","orcid":"0000-0003-1949-0161","position":9,"is_corresponding":false},{"id":498039,"name":"Wendy Max","orcid":"0000-0002-4040-1592","position":10,"is_corresponding":false},{"id":371769,"name":"M. G. Myriam Hunink","orcid":"0000-0002-2942-2798","position":11,"is_corresponding":false},{"id":577552,"name":"Bart S. Ferket","orcid":"0000-0003-2754-545X","position":12,"is_corresponding":false},{"id":1033501,"name":"José M. Rodriguez‐Valadez","orcid":"0009-0003-3297-538X","position":0,"is_corresponding":true}],"reference_count":67,"raw_metadata":null,"created_at":"2026-07-19T01:07:32.611759Z","pmid":"37220263","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}