Real-world effects of GLP-1 receptor agonists on cardiovascular-kidney-metabolic syndrome progression and lifetime costs in people with HIV and type 2 diabetes - people with HIV (PWH) are living…

The National Heart, Lung, and Blood Institute awarded Trustees of Boston University (doing business as Boston University Medical Campus) $837,125 on August 15, 2026, under the Cardiovascular Diseases Research program (CFDA 93.837) to conduct research on real-world effects of GLP-1 receptor agonists on cardiovascular-kidney-metabolic syndrome progression and lifetime costs in people with HIV and type 2 diabetes.

The research addresses a critical gap in evidence-based guidance for type 2 diabetes therapy in people with HIV (PWH), who face disproportionately high burdens of cardiovascular-kidney-metabolic syndrome and substantially higher rates of adverse cardiometabolic events than the general population. The study will examine whether and for whom GLP-1 receptor agonists—including liraglutide, semaglutide, tirzepatide, and dulaglutide—meaningfully alter cardiovascular-kidney-metabolic trajectories in PWH. Early studies demonstrate favorable effects of these agents on weight, glycemia, and liver health with good tolerability and no apparent compromise of HIV control, but existing evidence is short-term, underpowered for clinical outcomes, and excludes PWH from major trials, leaving critical uncertainty regarding long-term cardiometabolic value in this population.

The award runs through May 31, 2031, with place of performance in Roxbury, Massachusetts. Boston University Medical Campus holds this as a project grant under the NIH peer-review process, with scientific merit and program relevance evaluated by an initial review group and the National Heart, Lung, and Blood Advisory Council.

Real-world effects of GLP-1 receptor agonists on cardiovascular-kidney-metabolic syndrome progression and lifetime costs in people with HIV and type 2 diabetes - people with HIV (PWH) are living longer but face a disproportionately high burden of type 2 diabetes (T2D) and cardiovascular-kidney-metabolic (CKM) syndrome. Traditional cardiometabolic risk factors, non-traditional factors (e.g., hepatitis C, depression), chronic immune activation and inflammation, and antiretroviral therapy- associated weight gain accelerate CKM progression in PWH. Consequently, PWH often enter care at or beyond CKM stage 2 and experience substantially higher rates of CKM stage 4 events-including myocardial infarction, stroke, heart failure, and advanced kidney disease-than the general population. Despite this burden, evidencebased guidance on optimal T2D therapy for PWH remains limited. Newer therapies with cardiometabolic benefit include glucagon-like peptide-1 receptor agonists (GLP-1RAS; liraglutide, semaglutide, tirzepatide, and dulaglutide), incretin-based agents that improve glycemia, promote weight loss, and reduce cardiovascular risk, as well as sodium-glucose cotransporter-2 (SGLT2) inhibitors, which improve glycemia and reduce cardiovascular outcomes in the general T2D population. Older antidiabetes agents (e.g., metformin, sulfonylureas, thiazolidinediones, dipeptidyl peptidase-4 inhibitors), by contrast, primarily provide glycemic control with limited CKM benefit. GLP-1RAS may be particularly compelling for PWH, as early studies demonstrate favorable effects on weight, glycemia, and liver health with good tolerability and no apparent compromise of HIV control. However, these studies are short-term, underpowered for clinical outcomes, and provide no insight into CKM progression or long-term value. PWH have also been excluded from major trials, leaving critical uncertainty regarding whether-and for whom-GLP-1RAS meaningfully alter CKM trajectories in this population. Leveraging komodo health's nationally representative medical-claims database with linked clinical and laboratory data, we will compare GLP-1RA initiators with initiators of other non-GLP-1RA antidiabetes medications to estimate effects on CKM syndrome progression in PWH with T2D. The project will study 428,762 PWH with T2D during 2016-2025, including 26,241 GLP-1RA initiators. Aim 1 will quantify GLP- 1RA initiation, persistence, discontinuation, switching, and augmentation, and compare early adverse events with other antidiabetes medications. Aim 2 will estimate the causal effects of GLP-1RA initiation versus non- GLP-1RA antidiabetes medication on CKM progression (stage 4 primary outcome; stages 2-3 secondary/exploratory) using real-world target trial emulation and causal inference methods. In aims 1 and 2, we will evaluate differences in treatment effects by antidiabetes drug class and specific agents and assess heterogeneity across key demographic and clinical characteristics. Aim 3 will evaluate the long-term clinical and economic value of GLP-1RAS using the prime type 2 diabetes model, a validated simulation model of T2D complications and costs. We will deliver the first large-scale real-world evidence on GLP-1RA effectiveness and safety for preventing CKM progression in PWH with T2D, supporting nhlbi priorities.