Real-world cardio-kidney effectiveness of GLP-1 and GLP-1/GIP add-on therapy among SGLT2 inhibitor users
Description: People with type 2 diabetes are at high risk for heart and kidney disease. In recent years, new medications have been shown to improve blood sugar control, promote weight loss, and reduce cardio-renal risk. As a result, many patients are now treated with more than one of these therapies. However, there is limited evidence on whether adding newer glucose-lowering medications on top of existing therapies provides additional benefit for heart and kidney outcomes in routine clinical practice. Randomized clinical trials have demonstrated the benefits of individual drug classes, but they have not evaluated combination or sequential therapy as it is currently prescribed in everyday care. In particular, it remains unclear whether adding GLP-1 or GLP-1 and GIP receptor agonists to patients already treated with SGLT2 inhibitors further reduces cardio-renal risk, and whether these benefits are consistent across different patient groups. We propose to address this gap by studying adults with type 2 diabetes receiving care in the Veterans Health Administration, one of the largest integrated healthcare systems in the United States. This work builds on our prior efforts to create a large, well-characterized dataset of SGLT2 inhibitor and GLP-1 therapy users with validated exposure and outcome definitions. We will compare clinical outcomes among patients who initiate GLP-1 or GLP-1 and GIP receptor agonists as add-on therapy versus those who initiate alternative glucose-lowering treatments. Outcomes of interest will include progression of kidney disease, hospitalization for heart failure, and major cardiovascular events. The study will use a prespecified analytic framework designed to reflect real-world treatment decisions and to reduce bias common in observational research. Eligibility criteria and cardio-renal outcome definitions will be benchmarked to prior large clinical trials, while addressing treatment patterns that are increasingly common in routine care but unlikely to be studied in future randomized trials. The findings from this work will provide practical evidence to inform clinical decision-making, identify patients most likely to benefit from combination therapy, and support more equitable use of effective treatments. This project aligns with the American Heart Association mission by advancing knowledge to reduce cardiovascular risk and improve long-term health outcomes among people with cardio-kidney-metabolic disease.
Funder: American Heart Association
Amount: $300,000
Funding type: research
Funder scheme: GP1 Medications Among Individuals with CKM Disease
Start date: 2026-07-01
End date: 2028-06-30
Investigators: Julio Lamprea-montealegre, Julio Lamprea-montealegre
Institution: The Regents of the University of California, San Francisco
Funded outputs count: 0
Funder award ID: 26GLPCKMD1643242
OpenAlex ID: G613422480