The Role of Glucagon in Glucose Metabolism in Humans With and Without Bariatric Surgery

NCT07212868 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: STUDY00001597R01DK141843
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this study is to understand the role of glucagon signal on glucose metabolism in individuals with and without bariatric surgery. The study is involved with measuring glucose metabolism with glucagon infusion and glucagon receptor blockade. We use an investigational drug called REMD 477. "Investigational" means that the has not yet been approved by the U.S. Food \& Drug Administration (FDA). REMD-477 is a monoclonal antibody (an antibody made by cloning a unique white blood cell) that blocks the effect of glucagon.

Conditions

Non-Diabetic

Keywords

glucagon; glucose metabolism; bariatric surgery

Outcome Measures

Primary Outcomes (2)

• Glycemc response to meal ingestion

  Changes in glucose response to meal ingestion occurred by administration of glucagon receptor antagonist (GRA).

  0 to 240 minutes

• Endogenous glucose production (EGP) during clamp studies

  Changes in EGP (measured by tracer technique) with and without glucagon infusion

  0 to 240 minutes

Secondary Outcomes (3)

• Prandial glucose kinetics

  Baseline to 240 minutes

• Plasma GLP-1, GIP, insulin and glucagon concentrations

  0 to 240 minutes

• Glucose clearance and insulin and glucagon concentrations during clamp studies

  0 to 240 minutes

Study Arms (2)

Mixed Meal study with and without glucagon receptor antagonist

EXPERIMENTAL

Mixed meal test conducted with a sequential design of receiving a single dose subcutaneous injection of glucagon receptor antagonist or placebo.

Drug: REMD-477 versus Placebo

Pancreatic clamp (hypoglycemia and hyperglycemic) with and without glucagon infusion

OTHER

A cross-over study to compare the effect of glucagon infusion on glucose metabolism measured during clamp studies

Other: Exogenous glucagon versus saline infusion

Interventions

REMD-477 versus Placebo DRUG

Placebo versus glucagon receptor antagonist using a human monoclonal antibody with a high level of antagonistic effect against human glucagon receptor.

Mixed Meal study with and without glucagon receptor antagonist

Exogenous glucagon versus saline infusion OTHER

The effect of increased glucagon concentrations in plasma on glucose metabolism during glucose clamp will be studied.

Pancreatic clamp (hypoglycemia and hyperglycemic) with and without glucagon infusion

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed and dated informed consent form from participant.
• Male or female, ≤65 and ≥18 years old
• Subjects with history of gastric bypass surgery and sleeve gastrectomy more than a year since surgery and non-surgical subjects without history of gastrointestinal (GI) surgery
• HbA1c ≤6%
• Willing to adhere to the study intervention regimen
• Female subjects of childbearing potential must have a negative pregnancy test at screening and all the study visits, and must not be lactating
• Females of childbearing potential who are sexually active with a nonsterilized male partner must use at least one highly effective method of contraception from screening and must agree to continue using such precautions during the study.It is strongly recommended for the male partner of a female subject to also use male condom plus spermicide throughout this period. Cessation of contraception after this point should be discussed with a responsible physician. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception.

You may not qualify if:

• Diabetes
• Pregnancy/lactation
• Hgb \<11
• Current GI obstruction or chronic diarrhea
• Subjects who are not within the age range of 18- 65 years.
• Evidence of active cardiorespiratory, hepatic, gastrointestinal or renal disease.
• History of allergy to the administered drugs.
• History of, or any existing condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product, put the subject at risk, influence the subject's ability to participate or affect the interpretation of the results of the study and/or any subject unable or unwilling to follow study procedures.
• Substance dependence or history of alcohol abuse and/or excess alcohol intake
• Patients on ketogenic diet
• Prisoners or institutionalized individuals
• AST (SGOT) \> 3 times upper limit of normal
• ALT (SGPT) \> 3 times upper limit of normal
• History of clinical hypoglycemia documents based on Whipples' triad (ONLY for Aim 2)

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• The University of Texas Health Science Center at San Antonio: lead

Study Sites (2)

Texas Diabetes Institute - University Health System

San Antonio, Texas, 78207, United States

RECRUITING

University of Texas San Antonio

San Antonio, Texas, 78229, United States

RECRUITING

Study Officials

• Marzieh Salehi, MD, MS

  The University of Texas Health Science Center at San Antonio

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marzieh Salehi, MD, MS

CONTACT

210-450-8560; davism13@uthscsa.edu

Andrea Hansis-Diarte, MPh

CONTACT

210-567-3208; hansisdiarte@uthscsa.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Masking for participants
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Placebo controlled physiologic study

Study Record Dates

• First Submitted: September 22, 2025
• First Posted: October 8, 2025
• Study Start: February 25, 2026
• Primary Completion (Estimated): May 1, 2030
• Study Completion (Estimated): June 30, 2030
• Last Updated: March 12, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: At study end after analysis of data.

Locations

US (2)