Dr. Irving Kent Loh
Obesity is an epidemic in America, with some physicians characterizing it as an actual disease and not just the byproduct of bad behavior, that is, a lifestyle of excessive caloric intake and lack of exercise. Those lifestyle elements undoubtedly contribute to obesity, but there are likely genetic and metabolic disorders that may be a root cause as well.
Sorting causality is not the point of this article, but my focus is on management of obesity. This is important because of the associated life-threatening disorders that accompany overweight, e.g., diabetes, hypertension, sleep apnea, cardiovascular disease, cancer, respiratory disorders, and likely autoimmune diseases.
Compounding the medical and health issues are the societal pressures that typically favor being lean as being more attractive which in this age of social media makes influencers more impactful than healthcare professionals. This explains, perhaps, the multibillion dollar industry of weight loss strategies, often promulgated by celebrities for fun and profit, but funded by people interested in separating you from your discretionary income.
Books, articles, blogs, YouTube and TikTok videos, exercise protocols and equipment have pushed us in multiple directions, often with transient success, only to be frustrated by long-term recidivism. In my past clinical experience, there have been two factors that have led to voluntary longer term success, but they are heart attacks and open heart surgery … not to be recommended. Bariatric surgery has worked quite well, but it’s surgery nonetheless.
Hence the interest in drugs that actually seem to work in inducing weight loss. These are the GLP-1 agonists which were primarily developed to control blood sugar levels in Type 2 diabetics. Besides being effective in blood sugar control, they have also been demonstrated to positively impact cardiovascular disease. The two best known agents with these weight loss effects are semaglutide (Ozempic for diabetes, Wegovy for weight loss) and tirzepatide (Mounjaro for diabetes; not yet approved for weight loss). They work by mimicking two hormones secreted by the small intestine when you eat. One is the glucagon-like peptide-1 (GLP-1) and the other is glucose-dependent insulinotropic polypeptide (GIP). Both of these help with blood sugar control, but semaglutide mimics only GLP-1 and tirzepatide mimics both.
A happy observation was that significant weight loss was also observed in clinical trials. These so-called incretin hormones affect hunger by stimulating the brain to slow stomach emptying and thus enhance the feeling of hunger or stomach fullness, thus helping reduce caloric intake. Dose dependent weight loss with correspondingly better control of lipids, blood pressure and blood sugar levels have been demonstrated.
All sounds pretty great, so let’s review what also needs to considered before getting these meds. Adverse effects of medications that impact the GI tract are predictable. Problems noted include nausea, vomiting, diarrhea, abdominal cramps, and constipation. Although symptoms may improve with continued use, 3-7% subjects had to quit the clinical trials because of these side effects. More worrisome are rarer but more serious complications like pancreatitis, gall bladder disease, kidney failure, and hypoglycemic episodes if on other diabetic medications. The risk of certain tumors is possibly increased as well, so best to sort that out with your doctors before asking for this class of drugs.
Other downsides are that these meds are currently subcutaneous injections, although oral agents in this class are on the horizon. And, of course, they are expensive at about $1,000 per month if not covered by insurance, and weight may come back if the medication is stopped, even with continued dieting. And the weight loss demand for these meds has produced shortages for diabetic patients that truly need these drugs to survive.
The upside is that there are several new injectable and oral investigational products in various stages of development from a number of mainstream pharmaceutical companies. Obesity medications are projected to be a huge profit center for the pharmaceutical industry, which also means that if insurance is to cover it, there likely will be incremental pressure to raise premiums on all of us to cover those costs.
Another important problem to bear in mind is that although weight loss is achieved, it is not just fat that is removed from your body, but also muscle mass. This contributes to the facial and body changes reported. These current drugs cause a medically induced starvation physiology. Embarking on a rigorous physically active program that includes aerobic and resistance training may mitigate the muscle loss, but then again, doing a program like that with caloric restriction with a diet with plenty of whole grains, fruits, vegetable, lean protein, and minimal processed foods may achieve the desired weight loss without the risks and costs. So back to square one?
These are new uses for a drug class that has been around for over a decade, but adverse effects and mitigation strategies for primary use for weight loss are being investigated and are unknown at this time. But the risks of true obesity, not the cosmetic 10-20 pounds, have real downstream risks.
Irving Kent Loh, M.D., is a preventive cardiologist and the director of the Ventura Heart Institute in Thousand Oaks. Email him at [email protected].