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

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) 1-2 and 1-4 hours postdose; and BG >180 mg/dL 1-2 and 1-4 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 versus IG (1-2 hours: P =.0047; 1-4 hours: P =.0034). Lower proportions of patients had at least 1 BG value >180 mg/dL with NG versus IG (1-2 hours: P =.0034; 1-4 hours: P =.0068). iAUC and AUC were lower with NG versus IG (P =.025 and P <.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.