The breathless headlines about revolutionary injectable weight-loss drugs of Ozempic, Wegovy and Mounjaro and the oral version Rybelsus have been on over-drive for the past few months. Headlines professing “Staggering Weight-loss” and pondering whether a side-effect was a reduction in addictive behaviors of drinking and food obsessions. Should the pressing question be whether you wanted your weight-loss as an injection or a pill or the bigger issue of cost? With reports on “Insurers clamping down on doctors who prescribe Ozempic for weight loss” there are issues of shortage to patients who need the medications for their diabetes control and fairness of access based on income and. Insurers are becoming very nervous because these medications are expensive and 2/3rds of the people in the United States are obese or overweight, which would translate to a big demand.
Glucagon-Like Peptide-1 (GLP-1) was turned into a medication by originally synthesizing a peptide amino acid chain from a Gila monster. Adding to this unlikely source are other building blocks from the same family to form a cocktail of multi-receptor drugs. At the American Diabetes Association’s recent 83rd Scientific Sessions the premier research Banting Award Lecture was delivered by Dr. Matthias Tschöp who heralded the potential for this concept at an ADA meeting back in 2011.
His research came to market last year with the approval of the combination GIP/GLP-1 drug tirzepitide (Mounjaro). GIP is glucose-dependent insulinotropic polypeptide and it is not entirely clear how it contributes to weight loss. However, it targets an area in the brain that is important for appetite stimulation and helps to stimulate insulin secretion in the pancreas. The breakthrough was the paradigm shift of considering obesity as a brain disease and moving the search to a gut hormone receptor in the brain.
There are now Phase2 trials of a different dual combo using GLP-1/glucagon and there is also a triple cocktail drugs combining Glucagon, GLP-1, and GIP in a Phase 2 trial stage as well. (FDA approval is the target after larger Phase 3 trials.) Weight-loss with these current and newer medication range from 5% - 24% in clinical trials. People without diabetes lose more weight than those with diabetes and the multi-combo medications are showing more weight-loss than the single agent versions. These weight-loss number now rival or surpass the impact of bariatric surgery. Unlike surgery, these medications need to be taken for life, if a person stops taking the drug, there is a rebound gain in the range of 70% to 80%.
There was a lively debate at the ADA meeting chaired by Dr. Peters between Dr. Carol Wysham and Dr. Irl Hirsch on whether society could afford to use these new and expensive medications to treat people for weight issues. A major concern is how these costly treatments increase the divide between patients who can afford the medications or have insurance access. The other side argued that there were costs in societal stigma and complications from not treating weight issues that also have delayed health cost with a lower quality of life.
All medications have side effects, both long term and short term. Fortunately, we’ve had these types of agents on the market for 15 years. The benefits we’ve seen in terms of better glucose control are clear, and come with an additional proven heart and kidney protection. When it comes to weight loss they could also help, over the long haul, reduce the 200+ other conditions that are associated with obesity, including cancer, heart attacks, joint disease, sleep apnea and many others. However, best of all is to prevent obesity in the first place and having a healthy diet and exercising are always very important. With time we will hopefully be able to identify the multiple causes for excessive weight gain and create individualized, precision-medicine approaches to treating disorders of metabolism and help people live longer, healthier lives.
A small number of participants that did not demonstrate improvement, this could have been due to a few factors: the provider may not have made any of the suggested medication changes, or the patient may not have been taking the prescribed medications. Nine of the patients with a decrease were still in range at 70% or more. Over the next few months, the team will further analyze their data to determine what happened in each case and determine out how to improve their outcomes even more.
Ultimately, the team hopes to show, as they analyze the data, that the CGMs and the Tele-CGM system make it possible to provide better care, reduce the risk of depression and hospitalizations, and improve quality of life.
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Gila monsters are a poisonous lizard with venom that has a small peptide similar to human GLP-1.