Nasal Glucagon Reverses Insulin-induced Hypoglycemia With Less Rebound Hyperglycemia: Pooled Analysis of Clinical Trials

Overview

Journal J Endocr Soc

Specialty Endocrinology

Date 2024 Mar 6

PMID 38444629

Authors

Elizabeth Seaquist

Marga Gimenez

Yu Yan

Munehide Matsuhisa

Christi Yuting Kao

R Paul Wadwa

Yukiko Nagai

Kamlesh Khunti

Affiliations

Soon will be listed here.

Abstract

Background: Rebound hyperglycemia may occur following glucagon treatment for severe hypoglycemia. We assessed rebound hyperglycemia occurrence after nasal glucagon (NG) or injectable glucagon (IG) administration in patients with type 1 diabetes (T1D) and type 2 diabetes (T2D).

Methods: This was a pooled analysis of 3 multicenter, randomized, open-label studies (NCT03339453, NCT03421379, NCT01994746) in patients ≥18 years with T1D or T2D with induced hypoglycemia. Proportions of patients achieving treatment success [blood glucose (BG) increase to ≥70 mg/dL or increase of ≥20 mg/dL from nadir within 15 and 30 minutes]; BG ≥70 mg/dL within 15 minutes; in-range BG (70-180 mg/dL) 1 to 2 and 1 to 4 hours postdose; and BG >180 mg/dL 1 to 2 and 1 to 4 hours postdose were compared. Incremental area under curve (iAUC) of BG >180 mg/dL and area under curve (AUC) of observed BG values postdose were analyzed. Safety was assessed in all studies.

Results: Higher proportions of patients had in-range BG with NG vs IG (1-2 hours: = .0047; 1-4 hours: = .0034). Lower proportions of patients had at least 1 BG value >180 mg/dL with NG vs IG (1-2 hours: = .0034; 1-4 hours: = .0068). iAUC and AUC were lower with NG vs IG ( = .025 and < .0001). As expected, similar proportions of patients receiving NG or IG achieved treatment success at 15 and 30 minutes (97-100%). Most patients had BG ≥70 mg/dL within 15 minutes (93-96%). The safety profile was consistent with previous studies.

Conclusion: This study demonstrated lower rebound hyperglycemia risk after NG treatment compared with IG.

Clinical Trial Registration: NCT03421379, NCT03339453, NCT01994746.

Citing Articles

The Effect of 50% Dextrose on Serum Glucose Levels in Adult Hypoglycemic Patients: A Prospective Observational Study.

Al Saidi A, Al Shamsi M, Al Farsi A, Al Tubi S Cureus. 2025; 17(3):e80375.

PMID: 40078883 PMC: 11902882. DOI: 10.7759/cureus.80375.

Nasal Glucagon Reverses Insulin-induced Hypoglycemia With Less Rebound Hyperglycemia: Pooled Analysis of Clinical Trials.

Seaquist E, Gimenez M, Yan Y, Matsuhisa M, Kao C, Wadwa R J Endocr Soc. 2024; 8(4):bvae034.

PMID: 38444629 PMC: 10913376. DOI: 10.1210/jendso/bvae034.

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