Glucagon's effects on blood sugar in people with and without bariatric surgery

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

This study tests whether giving glucagon or blocking its receptor changes short-term blood sugar control in non-diabetic adults who either had bariatric surgery or did not.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 150 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: The University of Texas Health Science Center at San Antonio (other)
• Locations: 2 sites (San Antonio, Texas and 1 other locations)
• Trial ID: NCT07212868 on ClinicalTrials.gov

What this trial studies

This Phase 1 interventional study compares acute glucagon infusion versus saline and a single subcutaneous dose of the investigational glucagon-receptor antibody REMD-477 versus placebo to measure effects on glucose metabolism. Aim 1 uses a glucose clamp with and without glucagon infusion to measure immediate changes in glucose handling; Aim 2 uses two-day meal studies with continuous glucose monitoring (CGM) to compare responses after REMD-477 or placebo. Participants include non-diabetic adults (HbA1c ≤6%) with prior gastric bypass or sleeve gastrectomy >1 year ago and a matched non-surgical group. Safety monitoring includes liver enzyme testing about 8 weeks after REMD-477 dosing and multiple in-person metabolic study visits over a 3–6 month participation window.

Who should consider this trial

Good fit: Adults aged 18–65 without diabetes (HbA1c ≤6%), who either had gastric bypass or sleeve gastrectomy more than one year ago or have no history of GI surgery, and who can attend in-person visits and follow study requirements are the intended participants.

Not a fit: People with diabetes, HbA1c above 6%, recent gastrointestinal surgery, pregnant or breastfeeding individuals, or those outside the 18–65 age range are unlikely to benefit or qualify for this study.

Why it matters

Potential benefit: If successful, the work could clarify how glucagon affects post-meal and fasting glucose and help guide new approaches to managing glucose changes after bariatric surgery.

How similar studies have performed: Previous small human studies manipulating glucagon (infusion or receptor blockade) have demonstrated effects on glucose production and handling, but use of REMD-477 in post-bariatric populations is relatively novel.

Eligibility criteria

Inclusion Criteria:

1. Provision of signed and dated informed consent form from participant.
2. Male or female, ≤65 and ≥18 years old
3. 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
4. HbA1c ≤6%
5. Willing to adhere to the study intervention regimen
6. Female subjects of childbearing potential must have a negative pregnancy test at screening and all the study visits, and must not be lactating
7. 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.

Exclusion Criteria:

1. Diabetes
2. Pregnancy/lactation
3. Hgb \<11
4. Current GI obstruction or chronic diarrhea
5. Subjects who are not within the age range of 18- 65 years.
6. Evidence of active cardiorespiratory, hepatic, gastrointestinal or renal disease.
7. History of allergy to the administered drugs.
8. 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.
9. Substance dependence or history of alcohol abuse and/or excess alcohol intake
10. Patients on ketogenic diet
11. Prisoners or institutionalized individuals
12. AST (SGOT) \> 3 times upper limit of normal
13. ALT (SGPT) \> 3 times upper limit of normal
14. History of clinical hypoglycemia documents based on Whipples' triad (ONLY for Aim 2)

Where this trial is running

San Antonio, Texas and 1 other locations

• Texas Diabetes Institute - University Health System — San Antonio, Texas, United States (RECRUITING)
• University of Texas San Antonio — San Antonio, Texas, United States (RECRUITING)

Study contacts

• Principal investigator: Marzieh Salehi, MD, MS — The University of Texas Health Science Center at San Antonio
• Study coordinator: Marzieh Salehi, MD, MS

Conditions: Non-Diabetic, glucagon, glucose metabolism, bariatric surgery