Dr. Loh: Update on weight loss medications not sourced from social media
At the end of May 2023, I wrote column on the anti-diabetic drug class known as GLP-1 agonists, but best known to lay audiences as Ozempic or Wegovy (semaglutide) and the likely to be approved Mounjaro (tirzepatide).
I strongly suggest that if you are truly interested in these weight loss indications and cautions, you check out the column to review before reading this column, since I want to update a few topics that have since emerged.
What makes this a topic worth revisiting is that there are many investigational medications, including some oral ones, in this and related drug classes in various stages of clinical trials, on which I may be a principal investigator with the help with some of my regional colleagues (and their patients) if they are interested in participating.
To review, obesity is an epidemic in the developed world. Obesity has significant deleterious health implications for patients, as well as the cosmetic considerations that drive the social media frenzy. Clinicians want to improve the health of their patients. An industry estimate suggests that as many as 1.5 million heart attacks and strokes may be prevented if the achievable 15% weight loss threshold is met.
Indeed, a topline randomized clinical trial report reported that semaglutide reduced major adverse cardiovascular events by 20% compared to the control group. Heart failure patients also seem to significantly benefit as well. It would appear that the science validates the hype. The pharmaceutical industry is interested because there’s “gold in them thar ills.” So except for the budgets of federal and private insurers and, critically, of patients, this is a win-win effort for all stakeholders.
As I pointed out in my prior column, semaglutide has a brain-gut-GI tract connection as part of its mechanisms of action. There may be a role for reducing liver scarring in patients with non-alcoholic fatty liver disease, a not uncommon disorder in clinical practice. Polycystic ovary syndrome, especially as a contributor to infertility, is in the research crosshairs for this drug class. The brain connection may lead to its use in substance abuse patients, and in an exciting hypothesis, its anti-inflammatory actions may be helpful in slowing down the development of dementia.
These latter data are coming from a couple of Danish studies that are following diabetic patients to see if this class of medication will slow down progression of early Alzheimer’s. Since semaglutide does not seem to cross the blood-brain barrier (nature’s safety net for the brain), how it may work is hypothetical. It may be related to reducing neuroinflammation that damages the blood-brain barrier itself as well as the blood vessels that nourish the brain. Topline results may be available in 2026.
Other GLP-1 agonist drugs with additional mechanisms of action that may be even more effective than semaglutide are in development and are eagerly awaited for these and other indications, one of which may be in the treatment of Type 1 diabetes, not just Type 2 for which these drugs were originally developed. More competition will keep pressure on the cost which are already quite high if not covered by insurance and must be borne out of pocket.
Another worrisome report is that some overseas pharmaceutical companies may be illegally compounding not yet approved, but theoretically more effective drugs in this class, and are channeling them for underground or internet sales in our market for lower cost. These will be unregulated and non-FDA approved drugs with flashy marketing, touting similar benefits and pushing lower costs as the hook. This could be extremely dangerous and should be avoided, despite the come-on.
Other drug classes targeting Alzheimer’s work on another mechanism possibly related to clearing the deposition of tau proteins and their subsequent tangles that short-circuit and disrupt cognitive function. One of these drugs has been approved (with some notable adverse effects), but several others are in the pipeline. I’ll be writing more about these monoclonal antibody drugs especially if they come to my research team here next year.
Just remember that lifestyle changes play a role in mitigating the risk of cognitive decline. Since it’s difficult to pick your parents, your controlling lifestyle choices is important. This translates to staying active, eating a healthy diet, maintaining an appropriate weight, and managing the most important cardiovascular risk factors. That means additionally controlling your lipid values, blood pressure, managing your diabetes if you have it, and not smoking.
Irving Kent Loh, M.D., is a preventive cardiologist and the director of the Ventura Heart Institute in Thousand Oaks. Email him at drloh@venturaheart.com.
This article originally appeared on Ventura County Star: Dr. Loh: Update on weight loss medications not sourced from social media
