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Discovery, characterization, and clinical development of the glucagon-like peptides
Open accessAbstract
The discovery, characterization, and clinical development of glucagon-like-peptide-1 (GLP-1) spans more than 30 years and includes contributions from multiple investigators, science recognized by the 2017 Harrington Award Prize for Innovation in Medicine. Herein, we provide perspectives on the historical events and key experimental findings establishing the biology of GLP-1 as an insulin-stimulating glucoregulatory hormone. Important attributes of GLP-1 action and enteroendocrine science are reviewed, with emphasis on mechanistic advances and clinical proof-of-concept studies. The discovery that GLP-2 promotes mucosal growth in the intestine is described, and key findings from both preclinical studies and the GLP-2 clinical development program for short bowel syndrome (SBS) are reviewed. Finally, we summarize recent progress in GLP biology, highlighting emerging concepts and scientific insights with translational relevance.
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“Circulating levels of GLP-1 are low in the fasting or inter-prandial state but spike quickly following oral nutrient loads, thus stimulating insulin secretion from the pancreatic β-cells, inhibiting glucagon secretion from the α-cells and slowing gastric emptying, thereby reducing hyperglycemia in T2D (Figure 1).13,14”
From Management of type 2 diabetes, obesity, or nonalcoholic steatohepatitis with high‐dose GLP‐1 receptor agonists and GLP‐1 receptor‐based co‐agonists (2024) · cites this paper as [13]
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“A second incretin hormone, Glucagon-Like Peptide-1 (GLP-1), also potentiates glucose-dependent insulin secretion in animals and humans [6].”
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“Diketahui bahwa GLP-1 mengalami degradasi cepat ketika meninggalkan usus, sehingga hanya sedikit yang mencapai sirkulasi sistemik.(6,13-16)”
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“中枢作用抑制食欲 [ 10 ] 。这些作用机制使得 GLP-1R 激动 剂不仅具有良好的降糖效果 ， 还具备减重 、 心血管保护等 额外获益 [ 11 ] 协同的治疗新基准 [ 12 ， 13 ] 。 2025 年 6 月国产全球首个获批 的胰高血糖素受体 GCGR/GLP-1R 双靶减重药物玛仕度 肽上市用于长期肥胖患者的体重控制 [ 14 ] 。 在此基础上 ， GLP-1R/GIPR/GCGR 三重激动剂 （ 如瑞 他鲁肽 ） 的研发进一步推动了疗效边界。胰高血糖素受体 （ Glucagon Receptor ， GCGR ） 激动具备促进肝脏消耗 、 提高 基础代谢率的能力 ，…”
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Metadata
- Authors
- Drucker, D. J., Habener, J. F., & Holst, J. J.
- Affiliations
- Mount Sinai Hospital (CA)
- Harvard University (US)
- University of Copenhagen (DK)
- Corresponding author
- Drucker, Daniel J.
- Venue
- Journal of Clinical Investigation
- Published
- 2017-12-01
- Volume
- 127
- Issue
- 12
- Pages
- 4217-4227
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- PMC
- PMC5707151
- OpenAlex
- W2772059359
- Cited by
- 418
- References
- 105
- Citations by year
- 2026: 46 · 2025: 62 · 2024: 58 · 2023: 41 · 2022: 52 · 2021: 49 · 2020: 38 · 2019: 42 · 2018: 29
- FWCI
- 4.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
- Funders
- Canada Research Chairs, Canadian Institutes for Health Research (MOP123391)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- glucagon-like peptide-1, glucagon-like peptide-2, enteroendocrine hormones, insulin secretion, glucoregulation, intestinal mucosal growth, short bowel syndrome
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Glucagon-Like Peptide-1 Receptor Agonists, Animals, Diabetes Mellitus, Type 2, Humans, Short Bowel Syndrome, Structure-Activity Relationship, Glucagon-Like Peptide 1, Glucagon-Like Peptide 2, Drug Discovery
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