{"doi":"10.1002/ajh.27348","title":"<scp>GLP</scp>‐1 agonists and <scp>SGLT</scp>‐2 inhibitors in adults with sickle cell disease","abstract":"Acute and chronic organ damage are key drivers of early mortality in adults with sickle cell disease (SCD). Chronic kidney disease (CKD) occurs in approximately half of adults with SCD and a rapid decline in estimated glomerular filtration rate (eGFR) portends an increased risk of progression to end-stage kidney disease (ESKD) and mortality.1 Although renin-angiotensin-aldosterone system (RAAS) blocking agents are commonly used to treat SCD nephropathy, evidence for their effectiveness is limited to short-term studies with mixed results on preserving kidney function in patients with SCD.1 Glucagon-like peptide-1 (GLP-1) agonists and sodium-glucose cotransporter-2 (SGLT-2) inhibitors are two classes of medications for treating type 2 diabetes mellitus (DM). GLP-1 agonists promote glucose homeostasis by stimulating insulin release from pancreatic beta cells via the incretin effect. SGLT-2 inhibitors improve glycemic control by preventing the reabsorption of filtered glucose by the proximal tubules in the kidneys. In addition to improving glucose control, large-scale clinical trials have demonstrated that these agents may improve adverse cardiovascular and kidney outcomes, such as a reduction in risk of cardiovascular death or progression to ESKD.2 The benefits of GLP-1 agonists and SGLT-2 inhibitors on kidney function are independent of their blood glucose lowering effects in patients with DM and CKD, suggesting alternative reno-protective mechanisms for these therapies.2 The efficacy of GLP-1 agonists and SGLT-2 inhibitors on kidney function and their safety on SCD-related complications, such as vaso-occlusive pain episodes (VOEs), have not been studied in adults with SCD and DM. To address this, we retrospectively identified adults with SCD treated at the University of Illinois Chicago, Sickle Cell Center who were prescribed GLP-1 agonists or SGLT-2 inhibitors as an outpatient. Clinical and laboratory data were obtained from the electronic medical charting system, Epic System (Madison, WI). Data before treatment was defined as prior to the initial start date of GLP-1 agonists or SGLT-2 inhibitors. Data during treatment was defined as from the initial medication start date until date of treatment discontinuation, if applicable. Random serum glucose and creatinine concentrations were obtained from basic metabolic panels drawn as part of outpatient routine care. For each creatinine concentration drawn, we used the 2021 creatinine-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation to calculate eGFR. VOEs were defined as pain episodes requiring care in the emergency room, acute care center, or inpatient hospital setting. Baseline eGFR values were calculated by the means of each patient's first 3 available eGFR measurements. For one patient who was treated with both a GLP-1 agonist and SGLT-2 inhibitor, analysis was independently performed for each individual medication's treatment window. We calculated eGFR slope with linear mixed-effects models.3, 4 The fixed effects were population-level baseline eGFR and time. The random effects were intercepts and slopes grouped by individual, representing patient-level variability in baseline eGFR and eGFR slopes, respectively. Separate mixed effects models were generated for patients before and during treatment for GLP-1 agonists and SGLT-2 inhibitors. From these mixed effects models, we used the Best Linear Unbiased Prediction approach to estimate individual patients' eGFR slopes. The treatment effect of the GLP-1 agonists and SGLT-2 inhibitors were compared before versus during treatment using the Wilcoxon rank-sum test. Analyses were conducted using R version 4.3.1. Between February 2016 and April 2023, seven patients with SCD were treated with either a GLP-1 agonist or SGLT-2 inhibitor at our center (Table 1). The median age at the time of treatment initiation was 55 years (interquartile range [IQR], 51–57 years). Five patients were female, and all seven patients h","journal":"American Journal of Hematology","year":2024,"id":446670,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9524,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":334701,"name":"Anand Srivastava","orcid":"0000-0002-8109-1420","position":1,"is_corresponding":false},{"id":247061,"name":"Vimal K. Derebail","orcid":"0000-0002-7662-7497","position":2,"is_corresponding":false},{"id":351695,"name":"Jin Han","orcid":"0000-0003-0662-006X","position":3,"is_corresponding":false},{"id":351697,"name":"Robert E. Molokie","orcid":"0000-0003-3623-7395","position":4,"is_corresponding":false},{"id":269831,"name":"Victor R. Gordeuk","orcid":"0000-0003-4725-7295","position":5,"is_corresponding":false},{"id":292968,"name":"Santosh L. Saraf","orcid":"0000-0002-8584-4194","position":6,"is_corresponding":false},{"id":235843,"name":"Ryan Sun","orcid":"0000-0003-1176-1561","position":0,"is_corresponding":true}],"reference_count":7,"raw_metadata":null,"created_at":"2026-07-19T02:01:54.980444Z","pmid":"38655752","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":[]}