# Type 1 Diabetes Impacts of Semaglutide on Cardiovascular Outcomes (T1-DISCO)

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2022 · $618,131

## Abstract

PROJECT SUMMARY
Cardiovascular disease (CVD) and diabetic kidney disease (DKD) are the leading causes of morbidity and
premature death in youth and adults with type 1 diabetes (T1D). Recent advances in continuous glucose
monitoring (CGM) and automated insulin delivery systems have facilitated improved glycemic control, but the
residual risk of CVD and DKD remains high. Obesity and insulin resistance (IR) have also accompanied
intensive glycemic therapy and may accentuate arterial stiffness and endothelial dysfunction, each of which is
known to predict CVD in T1D. Thus, studies are needed to explore the cardio-renal impact of new adjunctive
therapies in T1D informed by the transformative cardiovascular outcome trials in type 2 diabetes (T2D).
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) mitigate major adverse cardiac events in adults with
T2D and support weight loss. Our group has characterized subclinical cardiorenal disease in young persons
with T1D, reporting abnormalities in cardiac function, central arterial stiffness, endothelial function, kidney
function, and insulin sensitivity. These cardiorenal abnormalities were also worse with increasing BMI. Our
group has also documented attenuated subclinical cardiac dysfunction and aortic stiffness with GLP-1RA
without increased risk of hypoglycemia or diabetic ketoacidosis, in both adults with T2D and in animal models
of diabetes. To date, limited data exist regarding CVD, IR or DKD-related outcomes in young adults with T1D
in response to GLP-1RA. Indeed in T1D, studies with GLP-1RA have focused primarily on weight and glucose
lowering. Thus, there is a gap in our understanding of the cardiorenal impact of these agents in T1D.
To evaluate the effects and underlying mechanisms of GLP-1RA on cardiovascular and kidney function as well
as insulin sensitivity in T1D, we propose a 6-month randomized, placebo-controlled, double-blind study in 52
young adults with T1D (ages 18-40 years) using once weekly subcutaneous semaglutide as a mechanistic
probe. The primary outcomes will be change in central and peripheral pulse wave velocity (PWV) by aortic MRI
and SphygmoCor. Additional outcomes will include subclinical cardiac function by cardiac MRI, endothelial
function by flow mediated vasodilatation (FMDBA), insulin sensitivity by hyperinsulinemic euglycemic clamps,
intraglomerular hemodynamic function by iohexol and p-aminohippurate clearance, albuminuria by urine
albumin-to-creatinine ratio, and glycemic variability by CGM. Innovative translational assessments of nitric
oxide (NO) bioavailability, endothelial NO synthase (eNOS) activation, reactive oxygen species
(ROS)/oxidative stress from endovascular J-wire biopsies and endothelial glycocalyx from sublingual
assessments will provide mechanistic insight.

## Key facts

- **NIH application ID:** 10507929
- **Project number:** 1R01HL165433-01
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Petter Bjornstad
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $618,131
- **Award type:** 1
- **Project period:** 2022-07-27 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10507929

## Citation

> US National Institutes of Health, RePORTER application 10507929, Type 1 Diabetes Impacts of Semaglutide on Cardiovascular Outcomes (T1-DISCO) (1R01HL165433-01). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10507929. Licensed CC0.

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