Single, dual and triple receptor agonists for treatment of obesity

In recent months, there has been discussion in the media and within the medical industry about medications that work on certain receptors in our bodies to help treat obesity. These receptors (called GLP-1 and GIP) are like switches that control different functions in our bodies. They're found in various places like our pancreas, brain, heart, blood vessels, immune cells, gut, kidneys, and even in our fat cells.

For the first time in a long time, we have effective treatments for obesity, especially in people who also have health problems like type 2 diabetes, heart disease, sleep apnoea, polycystic ovarian syndrome, liver disease, cancer, arthritis, and depression. Obesity happens when we consume more calories than we burn, and while we can't fix the latter with these medications, they can help reduce the amount we eat.

These medications work by decreasing our appetite, so we don't feel as hungry, and make us feel full for longer by slowing down how fast our stomach empties. For people with type 2 diabetes, they also help release insulin when needed, without causing low blood sugar like some other diabetes medications.

These medications are generally safe, especially when started on a low dose. The most common side effect is nausea, but this usually improves over time. Some people may feel sick if they take these medications together with metformin, another diabetes medicine. There haven't been any reports of major problems when these medications are taken with other drugs.

Most studies show that these medications don't cause pancreatitis or pancreatic cancer, but if someone has had pancreatitis before, they should be careful. Also, they're not suitable for people with a history of medullary thyroid cancer or Multiple Endocrine Neoplasia syndrome (MEN)-2.

According to the latest update from the Therapeutic Goods Administration (TGA) in September 2023, there might be a shortage of one of these medications called semaglutide (Ozempic), which activates the GLP-1 receptor, for the remainder of 2023 and 2024. This is because more people are using it for weight loss, even if they don't have diabetes. Some people criticise this; however there are few options for medically treating obesity.

Another medication called tirzepatide (Mounjaro) was approved by the TGA in 2023. It's a long-lasting medication that works on both GIP and GLP-1 receptors. It can help people lose 15 to 20 kilograms, especially when used in higher doses. It's mainly for people with type 2 diabetes, but like semaglutide, it can also help with weight loss in people without diabetes. It is recommended for patients to start on a low dose and increase it over time. The medication comes in a vial and needs to be injected with a syringe.

There have been some concerns about these medications affecting how quickly our stomachs empty before surgery or certain gastric procedures. Some patients had trouble emptying their stomachs properly when using these medications. An effective way of preventing this issue involves fasting for a longer period of time or consuming a liquid diet prior to certain procedures.

In the future, we're looking forward to even more effective medications that target not just one or two receptors but three. These "Triple G" receptor agonists could help patients lose even more weight because they might boost how much energy is expelled.

We live in hope of a brighter, less obese, future, thanks to these new treatments.

Written by Professor Jerry Greenfield of St Vincent's Clinic.

Professor Jerry Greenfield is Head, Department of Endocrinology, and Director, Diabetes Services, St Vincent's Hospital (Sydney). He is a consultant at St Vincent's Private Hospital. He undertook a PhD at the Garvan Institute (2001-2004) and a post-doctoral fellowship at the University of Cambridge, Addenbrooke's Hospital, United Kingdom (2005-2006). His other current positions and roles include: Head, St Vincent's Health Care Campus, Faculty of Medicine and Health, UNSW Sydney; Laboratory Head, Clinical Diabetes, Appetite and Metabolism, Garvan Institute of Medical Research; Executive Council Member, Australian Diabetes Society. He supervises a number of PhD Endocrinologists on the St Vincent’s Clinic Campus.

References

1. Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, Kiyosue A, Zhang S, Liu B, Bunck MC, Stefanski A; SURMOUNT-1 Investigators. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022 Jul 21;387(3):205-216. doi: 10.1056/NEJMoa2206038. Epub 2022 Jun 4. PMID: 35658024.

2. Raven LM, Stoita A, Feller RB, Brown C, Greenfield JR. Delayed Gastric Emptying with Perioperative Use of Glucagon-like Peptide-1 Receptor Agonists. Am J Med. 2023 Aug 9:S0002-9343(23)00499-0. doi: 10.1016/j.amjmed.2023.07.016. Epub ah