795-P: Elucidating the Role of Weight Loss and Glycemia with Observed Benefits of GLP-1 Receptor Agonist Treatment in Patients with T2D

Weight loss has been associated with reduced cardiovascular disease (CVD) risk in people with type 2 diabetes (T2D). Glucagon-like peptide-1 receptor agonists (GLP-1RA) are an advancement in T2D treatment that can regulate glycemia and promote weight loss. However, the impact of weight loss, independent of glycemic control, on real-world clinical outcomes is not well understood. Here, the Cleveland Clinic electronic health record system was utilized to investigate the independent contributions of glycemic control and body mass index (BMI) change on clinical outcomes such as CVD, chronic kidney disease (CKD), hypertension, dyslipidemia, and time to insulin initiation in patients with T2D treated with GLP-1RA. Patients (n=4161) with T2D seen at the Cleveland Clinic between 8/2/2005 and 12/31/2021 who initiated GLP-1RA treatment without documented congestive heart failure, insulin use, and/or an estimated glomerular filtration rate <30 mL/min at the time of treatment initiation were retrospectively analyzed. Patients were required to be receiving GLP-1RA treatment for ≥12 months and have <18 months between physician encounters. Independent of glycemic control, each 1% reduction in BMI was associated with a 4% reduction in CVD risk (P=.008) and a 3% reduction in insulin initiation risk (P=.002). Independent of BMI change, each 1% reduction in HbA1c was associated with a 4% reduction in CKD risk (P=.001) and a 16% reduction in insulin initiation risk (P<.0001). Associations between BMI variability and CVD (HR=1.12, P<.0001) and osteoarthritis (HR=1.09, P=.014) and between HbA1c variability and CKD (HR=1.73, P=.032) and hypertension (HR=1.07, P<.0001) were observed. Durable BMI reduction was associated with a 28% decrease in CKD risk (P=.016) and a 61% reduction in hypertension risk (P=.005). In the real-world setting, decreased BMI was independently associated with reduced risk of CVD, CKD, hypertension, osteoarthritis, and insulin initiation. Disclosure A.Sharma: None. B.Burguera: Research Support; Novo Nordisk. M.Kattan: Consultant; Renalytix, Verici, Research Support; Novo Nordisk, Bayer Inc. A.D.Misra-hebert: Research Support; Bayer Inc., Merck Sharp & Dohme Corp., Novo Nordisk. K.M.Pantalone: Consultant; AstraZeneca, Bayer Inc., Corcept Therapeutics, Diasome, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk, Sanofi, Research Support; Bayer Inc., Merck & Co., Inc., Novo Nordisk, Twin Health, Speaker's Bureau; AstraZeneca, Corcept Therapeutics, Merck & Co., Inc., Novo Nordisk. D.M.Rotroff: Research Support; Novo Nordisk, Stock/Shareholder; Clarified Precision Medicine. A.Mariam: None. E.Zacherle: None. A.Milinovich: Research Support; Novo Nordisk, Merck & Co., Inc., AbbVie Inc., Amgen Inc., Bayer Inc., Eli Lilly and Company, Twin Health. J.Bauman: None. D.S.Sugano: None. J.Noone: Employee; Novo Nordisk. J.R.Rajpura: Employee; Novo Nordisk. R.S.Zimmerman: Speaker's Bureau; Xeris Pharmaceuticals, Inc.