# Effects of SGLT2 Inhibition on Coronary Flow Reserve and Other Key Indices Relevant to Type 2 Myocardial Infarction Risk among Women with HIV

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $771,613

## Abstract

7. Project Summary/Abstract
US women living with HIV (WLHIV) on antiretroviral therapy (ART) face a three-fold risk of myocardial
infarction (MI) compared with women without HIV. Further, among WLHIV who present with MI, the majority
(56%) present with type 2 MI – oxygen supply/demand mismatch in the absence of atherothrombosis. Data
suggest that coronary microvascular dysfunction and excess epicardial adipose tissue (EAT) volume represent
salient processes relevant to type 2 MI risk among WLHIV. Our team aims to identify novel salutary
interventions. We propose a randomized controlled trial assessing the effect of sodium glucose transporter 2
(SGLT2) inhibitors on cardiac PET-derived coronary flow reserve (a CV risk surrogate reflecting the ability to
augment blood flow through large and small coronary arteries) and cardiac CT-derived EAT among WLHIV.
SGLT2 inhibitors, originally developed to treat DM2, work by blocking renal sodium/glucose reabsorption,
leading to glucosuria, as well as reduced glomerular perfusion pressure. Kidney- and cardio-protective effects
of SGLT2 inhibitors led to approval for use in CKD and heart failure, even among those without DM2. SGLT2
inhibition has been shown to improve coronary flow reserve and EAT in some patient populations but not
others. The observation that effects are population-specific highlights the need for testing among at-risk
WLHIV. Notably, newly published work from our group suggests SGLT2 inhibitors are rarely prescribed to
PLHIV with clinical indications in a large US healthcare system: <9% of PLHIV with DM2 and <4% of PLHIV
with DM2 and CKD. Randomizing WLHIV with a clinical indication (DM2, CKD, or both) to either SGLT2
inhibitor therapy + health education or health education alone x 24 weeks, we will: 1) Characterize effects of
SGLT2 inhibition on coronary flow reserve; 2) Characterize effects of SGLT2 inhibition on EAT; 3) Assess
whether changes in coronary flow reserve and EAT are predicted by baseline values of and/or associated with
changes in key kidney, metabolic, inflammatory parameters. Our central hypothesis is that SGLT2 inhibition +
health education vs. health education alone will result in a relative increase in coronary flow reserve and
reduction in EAT. Our work will likely identify a viable strategy to increase coronary flow reserve and reduce
EAT among WLHIV at risk for type 2 MI. Because this strategy is clinically available but underutilized among
WLHIV, evidence on favorable population-specific effects will be particularly informative. If SGLT2 inhibition
increases coronary flow reserve and/or reduces EAT among WLHIV, our work will yield mechanistic insights
into whether improvements relate to changes in kidney, metabolic, and immune/inflammatory parameters.
Even if SGLT2 inhibition yields disappointing results, our identification of novel factors associated with decline
in coronary flow reserve and/or increase in EAT among WLHIV will suggest alternate strategies to improv...

## Key facts

- **NIH application ID:** 11006470
- **Project number:** 1R01HL170905-01A1
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Markella V. Zanni
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $771,613
- **Award type:** 1
- **Project period:** 2024-09-01 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11006470

## Citation

> US National Institutes of Health, RePORTER application 11006470, Effects of SGLT2 Inhibition on Coronary Flow Reserve and Other Key Indices Relevant to Type 2 Myocardial Infarction Risk among Women with HIV (1R01HL170905-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11006470. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*