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The endocrine system is distributed throughout the body, enabling interorgan communication through liberation of chemical messengers, often steroid or peptide hormones, that communicate signals to organs and cells throughout the body. Classic endocrine organs include the pituitary, thyroid, and adrenal glands, as well as the ovary and testicles, with deficient hormone production producing many common clinical syndromes that may be treated using hormone replacement strategies. Clinical syndromes may also arise from excess hormone production, requiring therapeutic strategies to restrain or block hormone production.

Although less well studied, the gastroinestinal tract contains multiple subtypes of specialized endocrine cells that produce dozens of hormones, often small proteins, designated peptide hormones. These enteroendocrine peptide hormones regulate appetite, the motility of our gut, the secretion of pancreatic enzymes to aid food digestion, as well as the health and function of the lining of our gut that ensures optimal nutrient absorption.

Over the last few decades, considerable attention has focused on one type of gut endocrine cell, and its unique hormones, namely the gut endocrine L cell that secretes glucagon-like peptide-1(GLP-1). GLP-1 was first shown to control blood glucose throught its actions to stimulate insulin secretion. Subsequent studies demonstrated that GLP-1 also inhibits food intake, leading to weight loss. These findings led to the approval of the first GLP-1 medicine, exenatide, for type 2 diabetes in 2005, and in 2014, liraglutide was approved for treatment of obesity. The most popular GLP-1 medicines today are semaglutide and tirzepatide, that are administered once weekly for both type 2 diabetes and for obesity.

Interestingly, GLP-1 has been shown to have several additional actions that also contribute to its appeal as a therapeutic agent. GLP-1 medicines reduce the rates of heart attacks and strokes in people with type 2 diabetes, and they also improve cardiovascular health by reducing heart attacks and lessening the effects of heart failure in people with obesity. More recent studies have demonstrated benefits of GLP-1 medicines in people with obstructive sleep apnea, metabolic liver disease and diabetic kidney disease, and trials are underway in a range of substance use disorders, as well as Alzheimer’s disease. Hence, after almost 20 years of using these medicines in the clinic, their potential for improving human health across a wider range of indications continues to be explored. Going forward, it will be important to improve access to these live saving medicines by making the medicines easier to use, and less expensive, so that more people around the world can access these innovative new medicines to reducde the burden of their health challenges in a safe and cost-effective manner.

Canadian endocrinologist and a Fellow of the Royal Society, he is Professor of Medicine at the Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto. He is known for his research into intestinal hormones and their use in the treatment of diabetes, obesity, and other metabolic diseases, as well as intestinal failure.

By Daniel Drucker

Canadian endocrinologist and a Fellow of the Royal Society, he is Professor of Medicine at the Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto. He is known for his research into intestinal hormones and their use in the treatment of diabetes, obesity, and other metabolic diseases, as well as intestinal failure.