Good overview on Mounjaro, Zepbound and Obesity https://erictopol.substack.com/p/the-new-obesity-breakthrough-drugs

GLP-1 Update Mounjaro, Ozempic, Zepbound and Wegovy
April, 2024

1. American Association for the Advancement in Science (AAAS) gave their annual breakthrough award to 2 scientists—Lotte Bjerre Knudsen and Richard DiMarchi—the individuals who pushed to get these drugs to treat obesity.

2. Researchers Doctors Daniel Drucker, Joel Haebner and Jens Juul Holst —who discovered GLP-1 have been widely and appropriately recognized for their groundbreaking work on GLP-1 drugs.

3. Parkinson’s Disease: The GLP-1 drugs have now been shown to possibly slow the progression of Parkinson’s disease. GLP-1 drug Lixisenatide effects seem to be cumulative with benefits over a period of 5 to 10 years or more.

Interestingly Lixisenatide appears to be less effective for weight loss. One wonders whether the current GLP-1 drugs, semaglutide and tirzepatide would also be effective in slowing Parkinson’s and possibly other neurodegenerative disorders. It appears there is a gut-brain connection with these medications reducing inflammation.

4. Alzheimer’s: Two large randomized studies should be out by 2026 to answer whether GLP-1 drugs can suppress progression of Alzheimer’s.

5. Cardiac Disease: GLP-1 drugs reduced both cardiovascular disease and benefit patients with heart failure. Interestingly, the benefit may not be linked solely to weight loss.

6. Bottom Line: GLP-1 drugs appear to be the preferred treatment for diabetes.

Big Week for GLP-1 drugs
https://erictopol.substack.com/p/a-big-week-for-glp-1-drugs

Podcast with Doctors Daniel Drucker and Eric Topal
https://erictopol.substack.com/p/daniel-drucker-illuminating-the-glp

Lilly Press Release on Surmont-1 Results on Weight Loss

Once Weekly Treatment for Obesity Trial (Surmont-1)

Editorial in NEJM on Surmont-1 Study

New Study on Mounjaro/Zepbound: Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity

This study adds support that obesity is a disease and should be covered by insurance! Patients lost weight on the medication and gained weight when put on placebo. Not only did patients lose weight but also had improvements in cardiometabolic parameters including hemoglobin A1C, fasting blood glucose, insulin and lipid levels and improvement in blood pressure.

“The SURMOUNT-4 trial results emphasize the need to continue pharmacotherapy to prevent weight regain and ensure the maintenance of weight reduction and its associated cardiometabolic benefits.22 At least 5 trials (including the present study) across various classes of medications, including potent antiobesity medications such as semaglutide, have demonstrated that weight is substantially regained after cessation of pharmacotherapy.”

https://jamanetwork.com/journals/jama/fullarticle/2812936

Anti-obesity drugs’ side effects: what we know so far

The treatment of obesity has been revolutionized by new drugs such as semaglutide and tirzepatide. In clinical trials, these medications led to substantial weight loss — as much as an average of 21% of participants’ body weight¹ — and semaglutide has also been shown to cut the risk of severe cardiovascular problems, which specialists celebrated as a groundbreaking result.

A research letter published last week in JAMA² looked at a sample of people with obesity in a large health-insurance database. The authors found that the incidence of pancreatitis — inflammation of the pancreas — was 4.6 times higher in people taking semaglutide than in people taking a weight-loss medication that does not mimic GLP-1. The study also found that semaglutide and liraglutide, another GLP-1 medication, were associated with an increased incidence of gastroparesis, a disorder that slows or stops the movement of food from the stomach to the intestine.

https://www.nature.com/articles/d41586-023-03183-3

Tirzepatide (Mounjaro) is an imbalanced and biased dual GIP and GLP-1 receptor agonist
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526454/

The Science Behind How We Really Burn Calories – Scientific American https://apple.news/AcAITuGVQQ4y124vrqJPHBQ

Mounjaro Mechanism of Action