HM15136 is a novel long-acting glucagon analogue with an extended half-life. In vivo efficacy studies of HM15136 in animal models showed its therapeutic potential in congenital hyperinsulinism, hypoglycaemia post-bariatric surgery, and obesity. We performed a randomized, double‐blind, placebo‐controlled first-in-human trial to assess the safety, pharmacokinetics, and pharmacodynamics of a single subcutaneous dose of HM15136 in healthy adults. Fifty-six subjects of a mean age, BMI, and HbA1c of 31.1 years, 23.1 kg/m2, and HbA1c 5.2%, respectively, randomly received HM15136 or its matching placebo in a ratio of 6:2 in 7 cohorts (10, 20, 30, 50, 80, 100, and 120 µg/kg). All adverse events were mild in severity and transient. Neither serious adverse event nor discontinuation due to adverse event occurred during the study. The most frequent Treatment Emergent Adverse Event was nausea (7.2%, only in the 100 and 120 µg/kg groups). Injection site erythema, which was barely noticeable and spontaneously subsided without sequelae, was reported in 2 out of 42 subjects who received HM15136. HM15136 was slowly, but steadily absorbed with the peak serum concentration reaching 34.2-65.2 hours after dose. The terminal half-life ranged from 69.8 to 85.6 hours, which was significantly greater than that of glucagon (< 1 hour). HM15136, particularly at doses >50 µg/kg, increased mean serum glucose from baseline by up to 27.7 mg/dL, which was maintained until 17 days after dose.

In conclusion, a single subcutaneous dose of HM15136 at 10-120 µg/kg was safe and well-tolerated. The long half-life of HM15136, coupled with increase in serum glucose for ∼2 weeks, may warrant a weekly dosing regimen.


K. Huh: None. W. Shin: None. E. Baek: None. S. Seo: None. W. Lee: None. S. Baek: Employee; Self; Hanmi Pharmaceutical. H. Lee: None.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at