Dr. Irving Kent Loh
In late May 2023, I wrote an article about the class of diabetes drugs known as GLP-1 agonists, but more commonly known to the lay public as Ozempic or Wegovy (semaglutide) and most likely to be approved Mounjaro (tirzepatide).
I strongly suggest that if you are really interested in these weight loss guidelines and warnings, you watch the chronicle to review before reading this column, because I want to update a few topics that have emerged since.
What makes this a topic worth revisiting is that there are many investigational drugs, including some oral drugs, in this and related drug classes, in various stages of clinical trials , on which I could be principal investigator with the help of some of my regional colleagues. (and their patients) if they wish to participate.
To summarize, obesity is an epidemic in the developed world. Obesity has significant deleterious health consequences for patients, as well as aesthetic considerations that fuel the social media frenzy. Clinicians want to improve the health of their patients. An industry estimate suggests that up to 1.5 million heart attacks and strokes could be avoided if the achievable weight loss threshold of 15% is met.
Indeed, a randomized clinical trial report reported that semaglutide reduced major adverse cardiovascular events by 20% compared to the control group. Heart failure patients also appear to benefit significantly. It would appear that science validates this hype. The pharmaceutical industry is interested because there is “gold in these evils”. So, with the exception of the budgets of federal and private insurers and, most importantly, patients, this is a win-win effort for all stakeholders.
As I highlighted in my previous article, semaglutide has a brain-gut-GI tract connection as part of its mechanisms of action. It might be helpful to reduce liver scarring in patients with nonalcoholic fatty liver disease, a fairly common disorder in clinical practice. Polycystic ovary syndrome, particularly as a contributing factor to infertility, is in the focus of research into this class of drugs. The brain connection could lead to its use in drug-addicted patients, and in one exciting hypothesis, its anti-inflammatory actions could be useful in slowing the development of dementia.
This latest data comes from a few Danish studies that are following diabetic patients to see if this class of drugs will slow the progression of early Alzheimer’s disease. Since semaglutide does not appear to cross the blood-brain barrier (the natural safety net for the brain), how it works is hypothetical. This may be related to reducing neuroinflammation that damages the blood-brain barrier itself as well as the blood vessels that nourish the brain. The first results could 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 highly anticipated for these and other indications, one of which may be treatment type 1 diabetes, not just type 2 diabetes. which these drugs were initially developed. Increased competition will keep pressure on costs which are already quite high if they are not covered by insurance and must be borne out of pocket.
Another worrying report is that some foreign pharmaceutical companies may be illegally manufacturing not-yet-approved, but theoretically more effective, drugs of this class and funneling them into clandestine or Internet sales in our market at lower cost. These will be unregulated, non-FDA approved drugs with flashy marketing, touting similar benefits and driving down costs. This could be extremely dangerous and should be avoided, despite the arrival.
Other classes of drugs targeting Alzheimer’s disease work on another mechanism possibly related to the removal of tau protein deposits and their subsequent tangles that short-circuit and disrupt cognitive function. One of these drugs has been approved (with some notable side effects), but several others are in the works. I will write more about these monoclonal antibody drugs, especially if they come to my research team here next year.
Remember, lifestyle changes play a role in mitigating the risk of cognitive decline. Since it is difficult to choose your parents, it is important that you take control of your lifestyle choices. This means staying active, eating a healthy diet, maintaining an appropriate weight, and managing the most important cardiovascular risk factors. This also means checking your lipid values, your blood pressure, managing your diabetes if you have it and not smoking.
Irving Kent Loh, MD, is a preventive cardiologist and director of the Ventura Heart Institute in Thousand Oaks. Email him at drloh@venturaheart.com.
