NCT07131384

Interaction Between Inorganic Nitrate Supplementation and Metformin in Individuals With Prediabetes

The Interaction Between Inorganic Nitrate Supplementation and Metformin on Exercise Capacity, Vascular Function, and Insulin Sensitivity in Individuals With Pre-Diabetes

• Status: Not Yet Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 24 (estimated)
• Sponsor: University of Virginia · Academic / Other
• Sex: All
• Age: 18 Years – 60 Years
• Healthy volunteers: Not accepted

Summary

This study is examining whether short-term supplementation with inorganic nitrate, in the form of beetroot juice, can enhance blood vessel health, insulin sensitivity, and exercise capacity in individuals with prediabetes. We will be comparing the responses in individuals who are taking metformin to those who are naive to metformin. The results from this study may help identify non-pharmacological interventions in prediabetes.

Detailed description

One in 10 Americans have diabetes, with \~ 95% having type 2 diabetes (T2D). Another 1 in 3 have prediabetes, with 70% developing T2D during their lifetimes. Exercise is the standard of care for T2D. However, responses to exercise are blunted in T2D, in part due to the widespread use of metformin, which may inhibit mitochondrial function. Alternative therapies, such as inorganic nitrate supplementation, may provide benefits without attenuating exercise responses. Purpose: To examine inorganic nitrate supplementation on exercise tolerance, vascular function, and insulin sensitivity in subjects with PD (an ideal time to prevent progression to T2D) who are either taking or naïve to metformin pharmacotherapy. This study willl recruit twenty-four individuals with PD (12 on, 12 metformin naïve) will participate in a double-blind cross-over design after either oral nitrate or placebo supplementation, including: 1) tests of vascular function (pulse wave velocity, flow mediated dilation, microvascular function with post-occlusive reactive hyperemia, local thermal heating, and skin ACh iontophoresis); 2) exercise testing to determine VO2peak and lactate threshold; 3) an oral glucose tolerance test; and 4) an exercise time trial to exhaustion.

Conditions

• Males
• Females
• Sedentary
• Metformin
• Prediabetes

Interventions

Type	Name	Description
DIETARY_SUPPLEMENT	Dietary Supplement: Inorganic Nitrate (Beetroot juice)	Participants will be supplemented with inorganic nitrate in the form of beetroot juice for 4 days (12.9 mmol of NO3/day), and their vascular health, insulin sensitivity, and exercise capacity will be measured post-supplementation. This is a randomized crossover design with 2 parallel groups (Group 1: Currently taking metformin, Group 2: Naive to metformin).
DIETARY_SUPPLEMENT	Dietary supplement: Placebo (Nitrate-depleted beetroot juice)	Participants will be supplemented with nitrate-depleted beetroot juice for 4 days (\<0.01 mmol NO3/day), and their vascular health, insulin sensitivity, and exercise capacity will be measured post-supplementation. This is a randomized crossover design with 2 parallel groups (Group 1: Currently taking metformin, Group 2: Naive to metformin).

Timeline

• Start date: 2025-09-01
• Primary completion: 2026-12-01
• Completion: 2026-12-01
• First posted: 2025-08-20
• Last updated: 2025-08-26