PROJECT SUMMARY More than 12 million Americans currently live with both obesity and type 2 diabetes (T2D), putting them in one of the highest risk groups for developing serious microvascular and macrovascular complications. The Ameri- can Diabetes Association’s clinical practice guidelines recommend metabolic/bariatric surgery (MBS) and/or pharmacologic treatment of obesity for patients with obesity and T2D. In particular, glucagon-like peptide-1 re- ceptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) have both demonstrated efficacy in weight loss and preventing microvascular and macrovascular complications and are more accessi- ble than MBS. However, there are no long-term studies comparing GLP-1RAs or SGLT2is with MBS head-to- head with respect to effectiveness and safety, overall and in groups disproportionately affected by obesity and T2D but underrepresented in clinical trials such as racial and ethnic minority populations and rural residents. There is a clear and urgent need for large, real-world comparative effectiveness research studies to help pa- tients and their clinicians make evidence-informed decisions regarding the risks and benefits of surgical and medical approaches to reduce the long-term complications of concurrent obesity and T2D. We propose a com- parative effectiveness and safety study using administrative claims and linked electronic health record data on a diverse nationwide cohort (~40% racial/ethnic minority) of >500,000 patients with T2D and obesity treated with MBS, GLP-1RA, or SGLT-2i from 2010 to 2025, encompassing patients covered in commercial, Medicare Advantage, and 100% of Medicare fee-for-service plans. Our specific aims will compare the effectiveness of GLP-1RAs and SGLT-2is versus MBS in improving metabolic outcomes (weight, blood pressure, and hemoglo- bin A1c), reducing rates of micro- and macrovascular disease, and all-cause mortality among patients with obe- sity and T2D. We will also compare t