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Aims: To quantify changes over time in cardiovascular (CV) risk factor control and in the uptake of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 (SGLT2) inhibitors from 2007 to 2020 in a realworld community-based cohort of type 2 diabetes (T2D) patients. Materials and Methods:This study identified 95 461 T2D patients, who were followed for an average of 6.4 years through a single healthcare organization's electronic health record. The primary outcome was global risk factor control according to four factors ("ABCS"): glycated haemoglobin (HbA1c [<8%]); Blood pressure (systolic/diastolic <140/90 mmHg); Cholesterol (non-HDL cholesterol <130 mg/dL); and Smoking (not). Concomitant presence of microvascular complications and commonly used medication classes were tracked.Results: According to the ABCS metric, global risk factor control did not appreciably change over time; in 2020, 40.9% (95% confidence interval 40.2, 41.5) of patients had all four factors controlled. Among individual components, HbA1c control (<8%) worsened over time from 84% in 2007 to 78% in 2020, while lipid control (non-HDL cholesterol <130 mg/dL) improved from 59% to 72%.Coexisting microvascular complications were more prevalent over time; for example, neuropathy prevalence increased from 21% (2007) to 35% (2020). Use of thiazolidinediones and sulphonylureas decreased over time while metformin, insulin, dipeptidyl peptidase-4 inhibitor, GLP-1RA and SGLT2 inhibitor use increased. In 2020, GLP-1RAs and SGLT2 inhibitors were each used by 13% of T2D patients. Conclusions:In this community-based study, global CV risk factor control in T2D did not improve, although glycaemic control worsened and lipid control improved. Given increased uptake of GLP-1RAs and SGLT2 inhibitors, the collective effect of these changes on CV outcomes warrants evaluation.

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 &lt;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 &lt;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&lt;.0001). Associations between BMI variability and CVD (HR=1.12, P&lt;.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&lt;.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.

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