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Clinical Trial
. 2023 Sep;25(9):2723-2733.
doi: 10.1111/dom.15162. Epub 2023 Jun 13.

Safety, tolerability, pharmacokinetics and pharmacodynamics of multiple ascending doses of the novel long-acting glucagon analogue HM15136 in overweight and obese patients with co-morbidities

Wonjung Shin  1 , Marcus Hompesch  2 , JinHee Byeon  1 , Seohyun Kang  1 , Jaehyuk Choi  1 , Seungjae Baek  3
Affiliations
Clinical Trial

Safety, tolerability, pharmacokinetics and pharmacodynamics of multiple ascending doses of the novel long-acting glucagon analogue HM15136 in overweight and obese patients with co-morbidities

Wonjung Shin et al. Diabetes Obes Metab. 2023 Sep.

Abstract

Aim: To evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of multiple ascending doses of the novel long-acting glucagon analogue HM15136 in overweight/obese patients with co-morbidities, with and without type 2 diabetes (T2D).

Materials and methods: This was a phase 1, double-blind, randomized, placebo-controlled, two-part trial with a 12-week treatment period of once-weekly subcutaneous HM15136 (0.02/0.04/0.06 mg/kg). Part 1 included patients with dyslipidaemia and/or hypertension and no T2D. Part 2 included patients with dyslipidaemia and/or hypertension plus T2D.

Results: In part 1, 23/27 (85.2%) patients receiving HM15136 and all patients receiving placebo (9/9 [100%]) experienced a treatment-emergent adverse event (TEAE). Five of 27 (18.5%) patients receiving HM15136 developed anti-HM15136 antibodies. Dose-dependent increases in mean HM15136 serum concentration and fasting plasma glucose (FPG) were observed, as were dose-dependent weight reductions of 0.5%/2.3%/2.6% at doses of 0.02/0.04/0.06 mg/kg, respectively. In part 2, 8/12 (66.7%) patients receiving HM15136 and all patients receiving placebo (4/4 [100.0%]) reported a TEAE. Two (16.7%) patients developed anti-HM15136 antibodies. Dose-dependent increases in mean HM15136 serum concentration were observed. FPG of more than 200 mg/dL was reported in 4/9 (44.4%) and 2/3 (66.7%) patients receiving 0.02 and 0.06 mg/kg, respectively. The 0.06 mg/kg dose was not tolerated in part 2 because of hyperglycaemia. Patients receiving 0.02 mg/kg showed a 0.9% weight reduction. No serious TEAEs leading to discontinuation were reported in either study part.

Conclusions: This study of HM15136 provides a preliminary safety and tolerability profile with initial insights into its efficacy profile.

Keywords: glucagon; hypoglycaemia; pharmacodynamics; pharmacokinetics.

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References

REFERENCES

    1. Porcellati F, Di Mauro S, Mazzieri A, et al. Glucagon as a therapeutic approach to severe hypoglycemia: after 100 years, is it still the antidote of insulin? Biomolecules. 2021;11:1281.
    1. Arnoux JB, Verkarre V, Saint-Martin C, et al. Congenital hyperinsulinism: current trends in diagnosis and therapy. Orphanet J Rare Dis. 2011;6:63.
    1. Lobato CB, Pereira SS, Guimarães M, et al. A potential role for endogenous glucagon in preventing post-bariatric hypoglycemia. Front Endocrinol (Lausanne). 2020;11:608248.
    1. Al-Massadi O, Ferno J, Dieguez C, Nogueiras R, Quinones M. Glucagon control on food intake and energy balance. Int J Mol Sci. 2019;20(16):3905.
    1. Sánchez-Garrido MA, Brandt SJ, Clemmensen C, Müller TD, DiMarchi RD, Tschöp MH. GLP-1/glucagon receptor co-agonism for treatment of obesity. Diabetologia. 2017;60:1851-1861.

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