As the new year gets going, most people have already set some New Year's resolutions (here's some if you're of the science-y academic ilk) and chief among these is usually to exercise more and lose that holiday weight after the mounds of cookies and pie. It is perhaps not a coincidence that the latest Science Magazine Breakthrough of the Year recognizes GLP-1 drugs, which have been shown not only to be effective in managing diabetes, but also has significant impact on weight loss. The demand for these drugs has skyrocketed over the last few years as the word of their efficacy has spread, leading to supply chain issues that could adversely affect diabetes patients dependent on the medications. As the various GLP-1 drugs remain in short supply, it seems a good time to explore these drugs, their potential contributions to global human health, and what can be done to ensure they are accessible to those who need them most.
What's Up With GLP-1?
In high school biology, units dealing with metabolism and endocrinology often discussed insulin and glucagon, which had opposing effects in monitoring blood glucose levels. You can imagine that precise control of insulin and glucagon levels would be very important to good health, particularly to manage the symptoms in diabetic patients. The glucagon-like peptide-1, or GLP-1, is actually a cleavage product of a larger protein that produces glucagon as one of the four distinct products. Produced by the small intestine, GLP-1 has direct effects that include:
- Insulin release to lower blood glucose;
- The blockade of glucagon secretion to prevent a rise in blood glucose;
- Slowing down the digestive process in the stomach to reduce the rate of glucose release from food;
- Neurological effects that helps the host feel full.
GLP-1 agonists are designed to mimic these effects through a structure that is similar to the native GLP-1, and are meant to be injected subcutaneously, which sounds painful but probably isn't too far off from what diabetic patients do to check their blood sugar, or other individuals might experience when they use an epipen.
Do GLP-1 Agonists Actually Work?
The very short answer is yes! To elaborate, ever since the advent of semaglutide, which has become the go-to GLP-1 drug due to only requiring a once-weekly injection, and resulted in patients losing copious amounts of weight in a short time. The most famous and popular semaglutide drug is Wegovy, while a similar drug, Mounjaro, is a tirzepatide. Semaglutides like Wegovy and Ozempic are now being marketed as a weight loss drug, while Mounjaro claims the majority of users can drop their A1C levels below 7% and maintain that level as a primary diabetes medication.
In addition to these profound effects in reducing weight and managing diabetes, it was found that people suffering from obesity and heart failure taking semaglutide showed incredible improvement in their heart health, had the energy to exercise more, and reduced their risk of future heart attacks and strokes than those on placebos.
The Adverse Effects of GLP-1 Drugs
I was watching this Doctor Mike video about fake "direct to consumer pharmaceutical advertising" commercials from Saturday Night Live, and he pretty much covered all my thoughts whenever these commercials show up during TV shows or sports events. The commercial spends about 10 seconds telling you the name of the drug and what it is supposed to do while listing general symptoms of some disease, and then the remaining time is spent listing all the ways it can kill you. It is no different for Wegovy and Mounjaro and every other drug, in that they have to tell you that side effects include pancreatitis, gastroparesis (a slowing of the emptying of the stomach), and bowel obstruction, along with a potential for thyroid cancer. Other side effects of GLP-1 agonists include nausea, vomiting, and diarrhea, which, while not as terrible as, say, thyroid cancer, is still rather unpleasant (and seems to be shared by a lot of drugs advertised on TV, hmmm).
Another potential issue with GLP-1 agonists, particularly if used as a treatment for obesity, is the regaining of lost weight soon after discontinuing the medication. In this video from Harvard Medical School, it was stated that patients that discontinued semaglutide use would regain most of their lost weight within a year. Along with the other previously mentioned adverse effects, having to essentially take this drug forever could increase those risks for the patient. In related news, scientists at MIT recently developed a vibrating capsule to treat obesity, and it seems that mildly shaking the stomach is probably better than thyroid cancer and bowel obstruction (though I guess there's a chance the pill gets stuck).
Improving Accessibility to GLP-1 Drugs
The above article from MIT had a good point about the potentially prohibitive cost of GLP-1 agonists, especially if they must be taken perpetually to be effective. The goal of their research was to create a cost-effective and safe option for people who can't afford those types of drugs, similar to the motivation behind my friend Max's research into natural remedies for complex human diseases. I would be curious to see how their future clinical trials go after the favorable results they observed in animals.
The other challenge is in supply. Ever since semaglutide drugs were introduced, it appears a remarkable amount of people have been prescribed Wegovy or Ozempic in 2023 (Science claims 1.7% of the US population), and not all of them are using the drug as a diabetes treatment. As a result of this sharp increase in demand, drugs including Wegovy and Mounjaro have been in short supply since 2022, and hospitals have had to warn their patients that the shortage is unlikely to end anytime soon even with manufacturer efforts. This is personally affecting due to members of my own family desperate to try something new to attempt to lose weight, and also to the community as a whole, because affluent folks who could potentially be using Wegovy as a vanity option are preventing diabetes patients from getting their much needed medication. We are therefore looking at a situation where the remedy involves both effective manufacturing and physicians prioritizing those who most need the medication when they write prescriptions. The issues with price-gouging for medications can be talked about some other day, but look for a future BioChat episode about that soon!
In the future, as supply chains start moving quicker and patients become more educated about their options, people can benefit from this medical breakthrough that has plenty of positive potential despite the challenges we discussed here. And since this is a new year, don't forget to also exercise and eat right, which is definitely something I should do more of too, after I finish this last cookie.
