What does this research mean for the field?

In fasted individuals with postbariatric hypoglycemia, an initial microdose of glucagon produces a predictable increase in glucose via increased endogenous glucose production, whereas subsequent doses yield diminished responses. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

This study aims to quantify the glycemic response to microdoses of glucagon in individuals with postbariatric hypoglycemia (PBH).

June 7, 2026

1368-P: Glycemic Response to Glucagon in Patients with Post-Bariatric Hypoglycemia

Key Points

This study aims to quantify the glycemic response to microdoses of glucagon in individuals with postbariatric hypoglycemia (PBH).
Enrolled individuals with PBH (0 M, 12 F, mean age 51, mean BMI 31.24 kg/m²).
Administered serial glucagon microdoses (75-450 mcg) at 30-minute intervals in randomized order.
Measured glucose turnover using [6,6-2H2] glucose infusion and collected arterialized venous blood for analysis.
Initial glucagon doses resulted in significant increases in glucose and EGP (p<0.05).
Larger initial glucagon doses led to greater glucose increases, with subsequent doses causing smaller changes.
Incremental glucose and EGP showed a strong correlation (escalation: R=0.54, p=0.02; de-escalation: R=0.68, p=0.002).

Abstract

Introduction and Objective: Postbariatric hypoglycemia (PBH) is responsive to glucagon, but therapeutic doses may trigger recurrent hyper- and hypoglycemia and side effects. In this study, we quantified the dose response of glucose to microdoses of glucagon in individuals with PBH. Methods: Individuals with PBH were enrolled (0 M, 12 F, age 51.0 ± 11.1, BMI 31.24 ± 4.59 kg/m2). After an overnight fast, serial microdoses of glucagon were administered in either ascending or descending doses on 2 study days (randomized order, range 75 to 450 mcg, every 30 minutes) to determine glucagon-stimulated incremental glucose and EGP. Glucose turnover was measured with 6,6-2H2 glucose infusion. Arterialized venous blood was collected to measure glucose, 6,6-2H2 glucose and hormone concentrations. Results: Initial doses of glucagon induced the greatest increment in glucose (p0.05) and EGP (p0.05), with greater responses to larger initial doses. Subsequent doses induced smaller changes in glucose, irrespective of order of dosing, potentially due to reduced hepatic glycogen. Incremental glucose and EGP were correlated (escalation: R=0.54, p=0.02, de-escalation: R=0.68, p=0.002). Conclusion: The data demonstrates that in fasted individuals with PBH, the initial microdose of glucagon results in predictable increment of glucose due to an increase in EGP, while subsequent doses may not. This data will inform dose optimization for closed-loop glucagon delivery to prevent and treat severe hypoglycemia in PBH. Disclosure S. Brown: None. F. Bril: Consultant; Current; Novo Nordisk. Advisory Panel; Current; Novo Nordisk. Consultant; Current; Madrigal Pharmaceuticals, Inc. Advisory Panel; Current; Madrigal Pharmaceuticals, Inc. Consultant; Current; Boehringer Ingelheim International GmbH. Advisory Panel; Current; Boehringer Ingelheim International GmbH. E. Arevalo-Rios: None. L. Pei: None. G. Londono: None. R. Basu: None. A. Basu: Research Support; Current; Dexcom, Inc. M.E. Patti: Other - My institution receives research funding for clinical trial.; Current; Recordati S.p.A, Amylyx. Other - Data Safety Monitoring Board; Current; Fractyl Health, Inc. Funding DK 137518DK 036836T32 DK 007260DK 029953DK 085516

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Cite This Study

BROWN et al. (Fri,) studied this question.

synapsesocial.com/papers/6a250b2d7def13d035e1b390 https://doi.org/https://doi.org/10.2337/db26-1368-p

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