Obesity Innovation Lab’s Post

Name: How GLP1 RAs can help Weight Loss | Obesity Innovation Lab posted on the topic | LinkedIn
Uploaded: 2024-09-12T14:38:42.839Z
Duration: 6 min 32 s
Channel: Obesity Innovation Lab

Obesity Innovation Lab

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3mo

GLP1 Receptor Agonists in Weight Loss: Efficacy, Risks, and Benefits This video from Harvard Medical School explores the role of GLP1 receptor agonists (GLP1 RA), such as liraglutide and semaglutide, in managing weight loss. Dr. Lee-Shing Chang discusses FDA-approved medications for weight management, highlighting key studies like SCALE and STEP trials. The efficacy of GLP1 RAs is compared to other treatments, alongside the risks and benefits of using these medications. #WeightLoss #GLP1RA #ObesityTreatment #HarvardMedical #Endocrinology Credit: Lee-Shing Chang Harvard University Brigham and Women's Hospital

Transcript

Hi, my name is Doctor Lee Ching Chang and I'm an associate physician and endocrinologist at Brigham and Women's Hospital in Boston, MA. In this video, we'll be talking about GLP one receptor agonists and their use in weight loss. Key take away points from this video are to understand the major trials establishing GLP one receptor agonists efficacy for weight loss. When thinking about weight management, there are 5 medications that have been FDA approved for long term weight management as of 2021. Of these agents, Orlistat works by decreasing the digestion and absorption of fats at the level of the gastrointestinal tract. The other agents work in large part by regulating appetite at the level of the central nervous system. Two of them, liraglutide and semaglutide, are GLP one receptor agonists. We'll focus on these two agents in this video. Of note, there are multiple other GLP one receptor agonists that are available for use, all of which are associated with weight loss. However, only two, liraglutide and semaglutide, have specific FDA indications for long term weight management. GLP one stands for Glucagon. Like peptide one, GLP one is an incretin hormone produced by the L cells in the intestine in response to food intake. GLP One has multiple effects, and GLP One receptors are found throughout the body, including in the brain, the gastrointestinal tract, the pancreas, and other organs. GOP one has numerous actions from a weight loss and metabolic perspective. The most relevant actions are that it helps regulate appetite and lower glucose. GLP one is thought to act at the hypothalamus, regulating appetite by increasing satiety. GLP one also acts on the gut to slow gastrointestinal motility and to increase satiety. And it also acts on the pancreas to upregulate insulin secretion from pancreatic beta cells. Liraglutide and semaglutide share over 90% homology to native GLP one. Both liraglutide and semaglutide have been modified to reversibly bind to serum albumin in the body. This increases their half life. Both the regulated and semaglutide were initially approved as glucose lowering medications for use in type 2 diabetes. However, both have been found to induce significant weight loss in many individuals. Dedicated trials in individuals with overweight and obesity without type 2 diabetes have confirmed their efficacy for weight loss in non diabetic populations. The SCALE trial established liraglutide's efficacy in weight management. It was a double-blind randomized control trial comparing liraglutide at a dose of 3.0 milligrams given subcutaneously once a day to placebo in just over 3700 patients without type 2 diabetes and with a BMI either of at least 30 or of at least 27 with concurrent dyslipidemia or hypertension. Both groups also receive lifestyle modification counseling. After 56 weeks, patients in the liraglutide group lost the mean of 8.0 percent, or 8.4kg of their body weight, compared to 2.6% or 2.8 kilograms, in the placebo group. The STEP trials are a series of trials to study some magnetites efficacy in weight management. Step one was a double-blind randomized control trial comparing semaglutide 24 milligrams once weekly given subcutaneously to placebo. It enrolled just under 2000 patients without type 2 diabetes and similarly with a BMI of at least 30 or of at least 27 with at least one weight related coexisting condition. Both groups received lifestyle intervention. After 68 weeks, patients in the somatotype group lost a mean of 14.9% of their body weight, compared to 2.4% in the placebo group, for an estimated treatment difference of 12. 4%. More participants in the semaglutide group than in the placebo group achieved weight reductions of five percent, 10%, and 15% or more at week 68. For example, for weight reductions of at least 5%, the comparison was 86%. This Immaculate group versus 32% in the placebo group and 51% of participants in the semaglutide group lost 15% or more weight compared to only 5% in the placebo group. The take away point being significant weight reduction was seen with use of semaglutide once weekly. If you're wondering whether liraglutide or semaglutide is more effective for weight loss, the Step 8 trial helped to answer that question. The Step 8 trial randomized 338 participants to semaglutide with matching placebo or liraglutide with matching placebo. Participants did not have diabetes and had a BMI of at least 30 or of at least 27 with at least one weight related coexisting condition. After 68 weeks, the primary outcome showed significantly greater weight loss. Semaglutide compared to liraglutide. The mean weight change from baseline was 15.8% with semaglutide versus 6.4% with liraglutide for treatment difference of 94%. An important note is that continued use of GLP one receptor agonists is needed to support maintenance of weight loss. In the Step 4 trial, after semaglutide running period of 20 weeks, participants were randomized to either switch to placebo or to continue semaglutide. As you can see here, those who switched to placebo saw a regain in weight compared to those who continued semaglutide who continued to lose weight with continuing semaglutide. Thank you so much for watching. I hope you found this topic helpful.

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