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Diabetes

When insulin isn’t enough: targeting glucagon in type 1 diabetes

Nature Medicine volume 28, pages 2007–2008 (2022)Cite this article

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A phase 2 study fails to meet its primary endpoint, but the treatment — a glucagon receptor antagonist — shows clinically relevant improvements in glycemic control, warranting further investigation as a potential adjunct to insulin.

Most individuals with type 1 diabetes (T1D) do not achieve glycemic targets1, increasing the risk for long-term diabetes-related complications. Despite this, treatment of T1D has remained insulin centric and just one agent — pramlintide (an analog of the hormone amylin) — has been approved as an adjunct treatment, with uptake hindered by the need for regular pre-meal injections. Addressing dysregulation of glucagon (which promotes hepatic glucose production) has emerged as a promising strategy to mitigate hyperglycemia in patients with T1D. In this issue of Nature Medicine, Pettus et al.2 present results of a phase 2 randomized trial evaluating a glucagon receptor antagonist in patients with T1D.

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Fig. 1: Meal-related glycemic excursions despite insulin therapy.

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Authors and Affiliations

  1. Yale School of Medicine, Department of Pediatrics, New Haven, CT, USA

    Michelle Van Name & Jennifer Sherr

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  1. Michelle Van Name
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  2. Jennifer Sherr
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Correspondence to Jennifer Sherr.

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Competing interests

M.A.V. reports research support from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and Provention Bio. J.L.S. reports research support from the Juvenile Diabetes Research Foundation, Insulet, Medtronic and NIDDK; has served on advisory boards for Bigfoot Biomedical, Cecelia Health, Insulet, Medtronic Diabetes, StartUp Health Diabetes Moonshot and Vertex; and has done consulting work for Cecelia Health, Eli Lilly, Insulet, Medtronic and Zealand.

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Van Name, M., Sherr, J. When insulin isn’t enough: targeting glucagon in type 1 diabetes. Nat Med 28, 2007–2008 (2022). https://doi.org/10.1038/s41591-022-02019-3

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