Slow and Steady Wins the Race: 25 Years Developing the GLP-1 Receptor as an Effective Target for Weight Loss
Open accessAbstract
Recent evidence from clinical trials supports the efficacy and tolerability of glucagon-like peptide 1 (GLP-1) receptor agonists as useful agents for weight loss. Although originally developed as glucose lowering agents for people with type 2 diabetes, progress in research over the last 3 decades has demonstrated that GLP-1 receptor agonists act in the central nervous system to reduce food intake. This minireview summarizes key aspects of GLP-1 biology and the clinical studies supporting the utility of the GLP-1 receptor signaling system as a therapeutic target for weight loss.
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The weight loss effects of tirzepatide are reduced in patients with diabetes, a difference also observed with semaglutide 2.4 mg.
“the emerging data suggest that the weight loss effects of tirzepatide are reduced in patients with diabetes, a difference also observed in trials with 2.4 mg of semaglutide.2”
From GIPR/GLP-1R dual agonist therapies for diabetes and weight loss—chemistry, physiology, and clinical applications (2023) · cites this paper as [2]
The Clinical Trials With Semaglutide section reports less weight loss with semaglutide 2.4 mg in participants with diabetes in STEP 2 than in those without diabetes in STEP 1 (roughly 10% versus 15%). The Implications, Unanswered Questions, and Future Directions section discusses tirzepatide’s weight-loss effect relative to semaglutide 1.0 mg, but does not compare tirzepatide’s effects in people with and without diabetes. No page numbers are available in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredPharmacologic engagement of the GLP-1R is a proven strategy for treating hyperglycemia in diabetes and reducing body weight.
“Pharmacologic engagement of the GLP-1R is a proven strategy for treating hyperglycemia in diabetes and reducing body weight.”
From GIPR/GLP-1R dual agonist therapies for diabetes and weight loss—chemistry, physiology, and clinical applications (2023) · cites this paper as [2]
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- Authors
- Kumar, N., & D’Alessio, D. A.
- Affiliations
- Duke Medical Center (US)
- Corresponding author
- D’Alessio, David A
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2022-05-10
- Volume
- 107
- Issue
- 8
- Pages
- 2148-2153
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W4280612441
- Cited by
- 14
- References
- 36
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 2 · 2023: 3 · 2022: 1
- FWCI
- 0.43
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- glucagon-like peptide-1, GLP-1 receptor agonists, weight loss, obesity, type 2 diabetes, dietary intake, central nervous system, appetite regulation
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Glucagon-Like Peptide-1 Receptor Agonists, Diabetes Mellitus, Type 2, Humans, Hypoglycemic Agents, Weight Loss, Glucagon-Like Peptide 1
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