Anti-obesity drugs: the answer, or another useless bandaid?
The idea that a drug is going to fix problems our behavior causes is a fantasy, and we’re suffering for it.
Semaglutide, marketed under the pharmaceutical name “Wegovy,” has quickly gained notoriety in diabetes management as well as obesity treatment. So much so that in 2022, there were shortages of the drug in Australia. A recent trail also ascertained its utility as an obesity treatment in adolescents.
It was reported by NBC that “73% of those who received the medication had a weight loss of 5% or more as compared to 18% of those who received only the lifestyle intervention.” Proponents of the drug base their findings on adjustment to BMI scores in patients, namely the ratio of height to weight for an individual. That measurement, however, is deeply flawed. BMI is an inaccurate measurement of body fat content and doesn’t take into account in form: muscle mass, bone density, overall body composition, and racial and sex differences.
Dr. Mitch Lazar, PhD, one of the foremost researchers of diabetes in the world, notes in a science article (co-authored by Dr. Rexford Ahima) the problem of using BMI, as well as potential redirects for the field:
“There is an urgent need for accurate, practical and affordable tools to measure fat and skeletal muscle, and biomarkers that can better predict the risks of diseases and mortality. Advances to improve the measurement of obesity and related factors will help determine the optimal weight for an individual, taking into account factors such as age, sex, genetics, fitness, pre-existing diseases, as well as novel blood markers and metabolic parameters altered by obesity.”
Taking this into account, it is striking that while the BMI of patients was lowered, their insulin responsiveness was not ameliorated. This is likely due to the mechanism of action Wegovy utilizes, namely, utility of an adjusted GLP-1 agonist. GLP-1 regulates appetite in the brain, and through a series of cellular cascades in response, increases the amount of insulin in the blood. Surely, this is a good thing, seeing as the main treatment for severe diabetics involves daily insulin injections?
It seems, however, that the science might indicate otherwise. High amounts of insulin can lead to insulin resistance, which in turn can lead to type 2 diabetes, much the same way many hormones, and even neurotrophic cascade participants i.e. neurotransmitters can lead to increased tolerance and eventually resistance in patients. In rat studies, there is even evidence in relation to SSRI usage of dopamine resistance or re-wiring of circuitry in the brain causing a reduced response to dopamine. Meaning, the rats literally need their SSRI to maintain functionality in terms of completing tasks, setting goals, and in more robust psychologies (like humans) critical reasoning impacts could also be assumed.
So, not only is the success metric Wegovy uses flawed, but also it might contribute to long-term morbidity based on its promotion of a hyperinsulinemic state. On top of that, Wegovy wasn’t nearly as effective without exercise and diet change. Though I wish to stop to point out an additional flaw in the control group: “all received concurrent lifestyle intervention — counseling on healthy nutrition and physical activity — throughout the trial (emphasis mine).” The participants not directly monitored in the study received no social support structure to encourage those changes apart from sessions that merely informed them of their options.
How do they expect teens to not only make enough money (or their parents), but also maintain a routine of planning their diets, shopping for the food, and then cooking it. On top of exercise regimen changes, on top of treating their already existing health problems, on top of going to school and, well, growing up. The control group is essentially a sham. And, even with the sham control group acting as a sub-par metric for what they claim to measure as a cohort, Wegovy still needed a changed diet and exercise routine in order to be optimally effective.
In my eyes, diet change and exercise are the essential factor, and finding ways to implement those on a community-level is more effective as a treatment plan, because it does not risk the possible physiological repercussions of long-term administration of the medicine. As the former holy-grail of obesity treatment, bariatric surgery, displays–removed weight is mostly gained back after 3 years. And in Wegovy’s case, if the diet and exercise adjustments do not become a staple in the patient’s lives, the only way to consistently assure these improvements is to keep administering the drug, and as I’ve shown earlier, there is a huge risk of serious physiological complications.
To be fair, a small number of patients could actually benefit from this, ones whose disability precludes the capability of lifestyle changes necessary to regain health. A story featured on NBC details one such story:
“By the time Emmalea Zummo entered the study, her weight had shot up to 250 pounds. The 17-year-old from Jeannette in western Pennsylvania had been struggling with weight gain related to a hormonal condition called polycystic ovary syndrome, or PCOS, for years.
“I tried diets,” Zummo said. “I tried exercise. I’m in more sports than any other kid I know, and nothing would work. My body would just get used to the extra exercise, get used to the new diet and the weight would come back.”
When the opportunity came to participate in the study, Zummo jumped at it. “Even at the first appointment when they were explaining what the medication was, it was already like I felt lighter mentally,” she said.
She lost more than 70 pounds. Now, her weight has dropped to 170-180, “which I’m really happy about,” Zummo said. “I felt better within my own skin, which is something I never felt before.”
I do not deny that this is a small progression for the field in modulating appetite and a new treatment route for certain patients, but the fact that this $1300/month drug is being heralded as a transformative agent in the treatment of metabolic disorders screams the pharmaceutical companies are exploiting us. We need more community-support measures that help everyone improve their health through self-metabolic regulation, things like reducing food deserts, community exercise spaces and groups, as well as cooking and gardening classes and communal efforts towards maintaining those. The idea that a drug is going to fix problems our behavior causes is a fantasy, and we’re suffering for it.
Written by Jeremiah Ockunzzi, courtesy of Dr. Bart Rademaker, MD.