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

IF 3 Q2 ENDOCRINOLOGY & METABOLISM Journal of the Endocrine Society Pub Date : 2024-02-26 eCollection Date: 2024-02-19 DOI:10.1210/jendso/bvae034

Elizabeth Seaquist, Marga Giménez, Yu Yan, Munehide Matsuhisa, Christi Yuting Kao, R Paul Wadwa, Yukiko Nagai, Kamlesh Khunti

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

Clinical trial registration: NCT03421379, NCT03339453, NCT01994746.

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鼻用胰高血糖素可逆转胰岛素诱发的低血糖症，且反弹高血糖症较少：临床试验汇总分析。

背景：胰高血糖素治疗严重低血糖后可能会出现反跳性高血糖。我们评估了1型糖尿病（T1D）和2型糖尿病（T2D）患者鼻用胰高血糖素（NG）或注射用胰高血糖素（IG）治疗后发生反跳性高血糖的情况：这是对3项多中心、随机、开放标签研究（NCT03339453、NCT03421379、NCT01994746）的汇总分析，这些研究的对象是≥18岁的1型糖尿病或2型糖尿病患者，并伴有诱发性低血糖。比较了治疗成功[15 分钟和 30 分钟内血糖 (BG) 升至≥70毫克/分升或从最低点升至≥20毫克/分升]、15 分钟内血糖≥70毫克/分升、服药后 1 至 2 小时和 1 至 4 小时内血糖在范围内（70-180毫克/分升）以及服药后 1 至 2 小时和 1 至 4 小时内血糖>180毫克/分升的患者比例。分析了血糖 >180 mg/dL 的增量曲线下面积 (iAUC) 和用药后观察到的血糖值的曲线下面积 (AUC)。所有研究都进行了安全性评估：结果：使用 NG 与 IG 相比，血糖在范围内的患者比例更高（1-2 小时：P = .0047；1-4 小时：P = .0034）。NG 与 IG 相比，至少有一次血糖值大于 180 mg/dL 的患者比例较低（1-2 小时：P = .0034；1-4 小时：P = .0068）。不出所料，接受 NG 或 IG 的患者在 15 分钟和 30 分钟时获得治疗成功的比例相似（97%-100%）。大多数患者在 15 分钟内血糖≥70 mg/dL（93-96%）。安全性与之前的研究结果一致：这项研究表明，与 IG 相比，NG 治疗后反弹高血糖的风险更低：临床试验注册：NCT03421379、NCT03339453、NCT01994746。

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