NCT07300982

Studies of Insulin and Glucagon Action in the Liver

• Status: Not Yet Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Sponsor: Duke University · Academic / Other
• Sex: All
• Age: 18 Years – 45 Years
• Healthy volunteers: Accepted

Summary

This study examines how glucagon works to regulate glucose metabolism, based on new findings that suggest glucagon signaling in the liver has more than one role, and that these multiple roles can be opposing in nature. Understanding this biology provides an opportunity to develop new generations of glucagon-based drugs that target specific pathways, making them more effective at controlling blood glucose. Participants will complete paired, 5-hour hyperinsulinemic glucose clamp visits in which they receive either glucagon or saline infusions while blood glucose is maintained and frequent blood samples are collected. The primary focus is whether coordinated glucagon and insulin signaling enhances hepatic insulin sensitivity.

Detailed description

Volunteers will undergo screening for medical history, medication usage, and blood work; those who qualify will be offered participation. Study participation will last approximately 5-12 weeks depending on appointment availability and the number of infusions planned. This protocol involves two sets of paired procedures. Approximately 15 participants will complete each set of paired visits. Participants can opt to complete one set of paired visits or both sets of paired visits. Set 1: Each participant will complete two 5-hour hyperinsulinemic clamp procedures to examine the effects of glucagon on glucose metabolism while measuring systemic glucose turnover and related blood markers. The procedures will be identical, except for the final phase of the procedure when either saline or a stepwise glucagon infusion will be administered. Set 2: Each participant will complete two 5-hour hyperinsulinemic clamp procedures to examine the effects of insulin on glucose metabolism while measuring systemic glucose turnover and related blood markers. The procedures will be identical, except for the final phase of the procedure when either saline or a steady glucagon infusion will be administered.

Conditions

• Diabetes (DM)

Interventions

Type	Name	Description
DRUG	Glucagon	Glucagon infusion either graded (0.2→0.4→0.6 ng/kg/min) or continuous (0.4 ng/kg/min) during the final 90 minutes of a hyperinsulinemic glucose clamp. The graded or continuous glucagon infusions are given as a component of 2 separate protocols. Glucagon prepared per pharmacy/bedside protocol.
DRUG	Saline (placebo)	IV saline infusion during clamp for 90 minutes as control.

Timeline

• Start date: 2026-04-01
• Primary completion: 2029-12-01
• Completion: 2029-12-01
• First posted: 2025-12-24
• Last updated: 2025-12-24

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study