Journal
DIABETES
Volume 67, Issue 9, Pages 1710-1719Publisher
AMER DIABETES ASSOC
DOI: 10.2337/dbi18-0008
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Funding
- Canada Research Chairs Program
- Canadian Institutes of Health Research
- GlaxoSmithKline
- Merck
- Novo Nordisk, Inc.
- Intarcia
- Eli Lilly
- Novo Nordisk
- Pfizer
- Banting & Best Diabetes Centre-Novo Nordisk Chair in Incretin Biology
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Glucagon-like peptide 1 (GLP-1) was originally identified as a gut-derived incretin hormone that lowered glycemia through potentiation of glucose-dependent insulin secretion. Subsequent studies expanded the actions of GLP-1 to include inhibition of glucagon secretion, gastric emptying, and appetite, collectively useful attributes for a glucose-lowering agent. The introduction of GLP-1 receptor (GLP-1R) agonists for the treatment of diabetes was associated with questions surrounding their safety, principally with regard to medullary thyroid cancer, pancreatitis, and pancreatic cancer, yet cardiovascular outcome trials subsequently revealed reductions in rates of stroke, myocardial infarction, and cardiovascular death with a paucity of major safety signals. We discuss the controversies, unanswered questions, and established use of GLP-1R agonists from a mechanistic and clinical perspective. We highlight methods for detection and cellular sites of GLP-1R expression, key uncertainties, recent insights, and experimental caveats surrounding the use of GLP-1R agonists for the treatment of diabetes and the reduction of diabetes-related complications.
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