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This week, weight-loss medications have been making headlines again. Initially, it was reported that Eli Lilly, the firm responsible for the drugs Mounjaro and Zepbound, became the first healthcare enterprise worldwide to attain a trillion-dollar valuation.
These two medications, aimed at diabetes and obesity respectively, are raking in billions for the company. Additional GLP-1 agonist medications—a class that encompasses Mounjaro and Zepbound with the same active ingredient—have also been authorized to diminish the likelihood of heart attack and stroke among overweight individuals. Numerous people are optimistic that these miraculous medications will also address neurological and potentially substance use disorders.
However, this week we also discovered that, unfortunately, GLP-1 medications seem ineffective for individuals with Alzheimer’s disease. Furthermore, those who discontinue use of these medications upon becoming pregnant may face potentially harmful weight gain during their pregnancies. Additionally, some researchers are concerned that individuals are resorting to these drugs postpartum to shed pregnancy weight without comprehending the associated risks.
This information should remind us that there’s still much unknown about these drugs. This week, we will examine the ongoing inquiries related to GLP-1 agonist medications.
First, a brief overview. Glucagon-like peptide-1 is a hormone produced in the intestines that aids in regulating blood sugar levels. Yet, it appears to influence various aspects of the body as well. Receptors for GLP-1 have been identified in multiple organs and throughout the brain, according to Daniel Drucker, an endocrinologist from the University of Toronto who has extensively researched the hormone.
GLP-1 agonist drugs effectively replicate the hormone’s function. Numerous variations exist, including semaglutide, tirzepatide, liraglutide, and exenatide, marketed under names like Ozempic, Saxenda, and Wegovy. Some are recommended for select diabetes patients.
However, as these medications also seem to curtail appetite, they have gained immense popularity as weight loss solutions. Studies indicate that many individuals using them for diabetes or weight loss encounter unexpected side effects; for instance, their mental health enhances, or they feel less compelled to smoke or drink alcohol, as highlighted in research found. Additionally, it appears that these drugs promote the proliferation of brain cells in lab animals.
All of this seems optimistic. Yet, a few ambiguous areas remain.
Are they beneficial for our brains?
Novo Nordisk, a rival of Eli Lilly, produces GLP-1 drugs Wegovy and Saxenda. Recently, the company conducted a trial with oral semaglutide among individuals with Alzheimer’s disease who were experiencing mild cognitive impairment or mild dementia. The placebo-controlled study involved 3,808 participants.
Regrettably, the company discovered that the drug did not seem to delay the advancement of Alzheimer’s disease among the participants who took it.
This announcement was a significant letdown for the research community. “It was rather disheartening,” Drucker remarks, despite having had no anticipation of a “definitive success.” Alzheimer’s disease has been notoriously challenging to treat, and often, considerable damage has already occurred by the time individuals receive a diagnosis.
Nevertheless, he is one of many who is not entirely abandoning hope. Research indicates that GLP-1 might reduce brain inflammation and enhance neuronal health, and it appears to improve communication among brain regions. This suggests that GLP-1 medications could benefit the brain, according to Drucker. There remains a possibility that these drugs might help prevent Alzheimer’s in individuals who maintain cognitive health.
Are they safe prior to, during, or after pregnancy?
Other research released this week raises concerns about GLP-1 effects around the time of pregnancy. Currently, individuals are advised to plan to discontinue the medications two months before chances of conception. This is partly due to some animal studies indicating potential harm to fetal development, but primarily because the effects during human pregnancy haven’t been thoroughly examined.
Among the general population, studies suggest that many individuals using GLP-1s for weight loss regain much of their lost weight once these medications are halted. Therefore, it might not be surprising that a study published in JAMA earlier this week observed a similar phenomenon in expectant mothers.
The research concluded that those who had been using these medications gained approximately 3.3kg more than individuals who had not. Furthermore, those who had used the drugs seemed to have a marginally elevated risk for gestational diabetes, blood pressure abnormalities, and even preterm labor.
This appears quite concerning. However, a different study published in August reported the opposite conclusion—it noted a decrease in those risks among women who used the medications prior to pregnancy.
If you’re confused about how to interpret all this, you’re not alone. There’s still no definitive guidance on how these drugs ought to be utilized before or during pregnancy.
Another study published this week revealed that people (in Denmark) are increasingly using GLP-1 medications postpartum to shed weight gained during pregnancy. Drucker notes that he frequently receives inquiries regarding this potential application.
However, numerous changes occur in a postpartum body. It’s a period of considerable physical and hormonal transformation that can include bonding, breastfeeding, and even neural reorganization. The effects of GLP-1 on any of these aspects remain unknown.
How—and when—is it safe for individuals to discontinue use?
Furthermore, another study released this week—indicative of the prominence of GLP-1s in current medical discourse—examined the fate of participants when they ceased taking tirzepatide (branded as Zepbound) for obesity management.
Participants were administered the drug for 36 weeks, after which half continued the medication, and the other half were switched to a placebo for an additional 52 weeks. During the initial 36 weeks, improvements in weight and heart health were observed among participants.
However, by the conclusion of the study, the majority of those who transitioned to placebo had regained over 25% of the weight they had originally lost. One out of four regained over 75% of that weight, and 9% ended up weighing more than they had at the study’s start. Their heart health also deteriorated.
Does this imply that individuals must use these medications indefinitely? Scientists lack a definitive response to that question, as well as the safety of prolonged use of these drugs. The answer may vary by individual, their age or health condition, and the intended purpose of the medication.
There are still other unresolved issues. GLP-1s show potential for substance use disorders, yet their efficacy remains undetermined. We also do not understand the long-term repercussions these drugs have on children who take them. Furthermore, the lasting effects of GLP-1s on individuals with a healthy weight using them for weight loss remain unclear.
Earlier this year, Drucker received a Breakthrough Prize in Life Sciences at a glamorous event in California. “Many of the Hollywood personalities were approaching me and expressing their gratitude,” he recalls. “Numerous individuals do not need to be utilizing these medications.”
This article initially appeared in The Checkup, MIT Technology Review’s weekly biotechnology newsletter. To receive it in your inbox every Thursday and to view articles like this first, subscribe here.
