Are weight-loss meds the next wonder drugs?

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If the COVID-19 vaccines were the most significant FDA approvals of the 2020s so far, GLP-1 agonists to treat obesity are a strong runner up.

Though these drugs have been used to treat type 2 diabetes for nearly two decades, it wasn’t until 2021 that the FDA approved one of them — Novo Nordisk’s Wegovy (semaglutide) — as a treatment for obesity. Clinical trials showed that people lost 10-20% of their body weight.

This was huge. An estimated 42% of adults in America are classified as obese, which puts them at increased risk of many serious health issues, including heart disease and some cancers, and death. The standard prescriptions prior to this — diet changes and exercise — are notoriously hard for many people to implement and stick to.

Trial participants ended up with lower blood pressure, blood sugar, and cholesterol.

GLP-1 agonists make it easier to lose weight by mimicking a hormone our bodies release naturally about 15 minutes after we start eating — this reduces our appetite and triggers the release of insulin, which helps take sugar out of our blood and convert it into energy.

In addition to helping people shed pounds, some GLP-1 agonists also have a proven ability to reduce weight-related health issues, such as heart attacks and deaths from cardiovascular disease. In clinical trials, people on the drugs ended up with lower blood pressure, blood sugar, and cholesterol, and some studies suggest the meds could treat fatty liver disease, too.

But evidence is mounting that they could treat other health issues — including ones that aren’t obviously related to weight. Researchers are now taking a closer look at these other potential indications for GLP-1 agonists. Here’s what they’re finding out.

Parkinson’s is a neurodegenerative disorder caused by the death of specific neurons in the brain. This causes problems with movement, mental and behavioral changes, and often premature death. While existing treatments can help control symptoms, none can stop the disease from progressing.

For a recent phase 2 trial, French researchers gave 156 people in the early stages of Parkinson’s a GLP-1 agonist (lixisenatide) or placebo every day for 1 year. Compared to at the start of the trial, the motor symptoms of people in the placebo group were slightly worse by the end of the year, while the treatment group’s motor symptoms remained essentially the same.

The results of a phase 3 trial testing a GLP-1 agonist as a Parkinson’s treatment are expected in 2024.

It’s not clear why this is happening — it may have something to do with the known but not well-understood connection between Parkinson’s and diabetes. This was a fairly small study and a lot of questions remain to be answered, including whether GLP-1 agonists could help people with more advanced Parkinson’s, halt the progression of Parkinson’s motor symptoms over a longer period, or prevent other types of symptoms, such as ones related to cognition, from worsening.

Still, with up to one million Americans affected by Parkinson’s, these results are highly encouraging, and the results of a larger phase 3 trial testing another GLP-1 agonist (exenatide) as a Parkinson’s treatment are expected in 2024.

Some people taking GLP-1 agonists for weight loss or diabetes have reported an unexpected, but often welcome side effect: decreased cravings for drugs, alcohol, and tobacco.

“GLP-1 receptors are located in the areas of the brain associated with both food and drug reinforcement,” Dr. Luba Yammine, associate professor of psychiatry at UTHealth Houston, told Freethink. “Additionally, brain mechanisms that contribute to overeating overlap with those that facilitate drug seeking behaviors. It is plausible that GLP-1 agonists could decrease reward (i.e., pleasure) and cravings for addictive substances.”

Plausible, but not confirmed. Several animals studies have found that GLP-1 agonists can reduce drug and alcohol seeking behavior, but there isn’t strong data from human trials: one small trial found that GLP-1 agonists could reduce opioid cravings, for example, while another found they could reduce cravings for alcohol, but only in people who were living with obesity.

Trials are ongoing, though. The National Institute on Drug Abuse is sponsoring one focused on alcohol addiction, and Yammine is leading two trials in people who are addicted to nicotine.

“In both of our trials, we incorporate measures to assess not only whether GLP-1 agonists ‘work,’ but also examine how they work via interrogating the hypothesized mechanisms,” she told Freethink, adding that they anticipate having trial results in about 2-3 years.

Because drug and alcohol addiction are, like obesity, unfortunately common in the US, if GLP-1 agonists prove to be effective treatments for any of these substances, this is another area where the medications could have a huge impact.

People with sleep apnea stop and start breathing again repeatedly while sleeping, usually because something is blocking their airway. This can prevent them from getting restful sleep, leading to daytime fatigue.

Obesity is one of the top risk factors for sleep apnea, which suggests that GLP-1 agonists could treat the condition by helping people lose weight. To get the FDA to approve the meds as sleep apnea treatments — and encourage insurance companies to cover them as such — drug makers need to prove the connection, though.

In April 2024, the pharma company reported the topline results of a trial that found that people with obesity and sleep apnea who took tirzepatide (brand name Zepbound) for a year lost an average of 20% of their body weight — and experienced a far larger reduction in apnea-related events at night than people taking a placebo.

Based on these results, Eli Lilly plans to submit an application to the FDA in mid-2024 to get tirzepatide approved as a sleep apnea treatment.

“While there are pharmaceutical treatments for the excessive sleepiness associated with [obstructive sleep apnea], tirzepatide has the potential to be the first pharmaceutical treatment for the underlying disease,” said Jeff Emmick, senior VP of product development at Eli Lilly.

In the US, about 10% of people of reproductive age have problems getting pregnant. Carrying excess weight is a risk factor for infertility, as is being diagnosed with polycystic ovary syndrome (PCOS), a hormonal condition that can also lead to weight gain.

Based on the promising results of small trials, doctors have been prescribing GLP-1 agonists off-label to people with PCOS for several years, and in addition to helping them lose weight, it also seems to be making it easier for them to get pregnant. Some people who started taking GLP-1 agonists to treat obesity or diabetes have also reported improved fertility.

Why this is happening isn’t clear — losing weight might simply increase fertility in both men and women, or perhaps the meds are interfering with birth control (although this wouldn’t apply to those trying to get pregnant). But researchers are looking closer at the connection, not only in the hope that GLP-1 agonists could be a new fertility treatment, but also to make sure it’s safe to be on the drugs during early pregnancy.

“The ‘oops’ babies on Ozempic and Wegovy are happening all over the place,” Melanie Cree, director of the PCOS clinic at Children’s Hospital Colorado in Aurora, told Bloomberg. “It’s very exciting, but it’s a bit scary because we’re moving forward without all the data.”

Obesity correlates with an increased risk of developing many mental health issues, including depression, anxiety, and bipolar disorder. At the same time, the meds to treat those issues often lead to weight gain, which can discourage patients from staying on them.

So far, early research and anecdotal reports from patients suggest that GLP-1 agonists may positively affect some mental health issues. The meds have been shown to reduce depression symptoms in studies of people with diabetes, and preclinical research suggests they might be able to reduce metabolic dysfunction and cognitive impairments linked to schizophrenia, too.

One report found that people with diabetes who took GLP-1 agonists were less likely to be diagnosed with depression or anxiety later — however, this is observational research, which can’t prove cause and effect.

More research is needed to confirm any potential connection between GLP-1 agonists and mental health, but several trials are ongoing. If the drugs can treat or prevent psychiatric problems, the impact could be huge, given that 20% of Americans live with a mental illness and many don’t have an effective treatment.

“There is evidence that GLP-1 agonists have direct effects on the brain, including an ability to restore dopamine imbalance,” Roger McIntyre, a professor of psychiatry and pharmacology at the University of Toronto, told Psychiatric News in December 2023. “What if these agents are psychiatric drugs that are masquerading as weight-loss drugs?”

Alzheimer’s is a progressive neurodegenerative disorder characterized primarily by problems with memory and cognition. The exact cause is unknown, but the most common genetic risk factor for Alzheimer’s is a gene involved in cholesterol transport in the brain, and diabetes appears to be a risk factor, too.

Suggestive but not conclusive evidence — preclinical studies, small clinical trials, and anecdotal reports — has found that GLP-1 agonists might improve memory, reduce rates of dementia, and more, suggesting they may be effective Alzheimer’s treatments.

“GLP-1 agonists are known to affect inflammation, and so my hypothesis would be that they are helpful through a modulation of the brain’s inflammatory response to the Alzheimer’s disease proteins,” Ivan Koychev, a clinical academic psychiatrist, told Freethink. “Alternatively, we know that these medications reduce the risk of strokes and so it could be that they help by preventing vascular events that contribute to dementia.”

To explore the possible connection between Alzheimer’s and GLP-1 agonists, Novo Nordisk launched two phase 3 trials — EVOKE and EVOKE plus — in 2021. Those trials will see a total of 3,700 people with early stage Alzheimer’s given semaglutide or a placebo for up to 3.3 years to test if the med has a positive impact on cognitive decline. A Novo Nordisk spokesperson told Freethink they expect both trials to wrap up in 2025.

Meanwhile, Koychev is leading a trial at Oxford University that’s studying the impact of semaglutide on the buildup of tau in the brains of people at elevated risk of developing Alzheimer’s because they already have high levels of amyloid in their brains. Those results are expected next year, as well.

Based on the evidence so far, it seems likely that GLP-1 agonists will eventually be approved to treat some conditions beyond diabetes and obesity, even if they don’t deliver on every potential benefit. However, the “wonder drugs” aren’t without their downsides.

People taking GLP-1 agonists often experience gastrointestinal problems, such as nausea and diarrhea, and some data suggests that the meds may increase the risk of rare but serious gastrointestinal issues, including stomach paralysis.

In 2023, the FDA launched an investigation after GLP-1 agonist users started reporting thoughts of suicide — as of January 2024, it hadn’t found anything to confirm the connection, but it also said it couldn’t yet rule it out, meaning its possible the drugs could cause mental health issues for some people, rather than treating or preventing them.

GLP-1 agonists also have to be taken indefinitely for weight loss to last — most people who stop taking them gain back the lost weight. It’s possible the same would be true for other benefits, and some people might not want to get on the drugs knowing they’d have to take them forever.

Ultimately, we’re still in the early stages of understanding what GLP-1 agonists are capable of, but with countless research teams all taking a closer look at the meds, it won’t be long before we have answers — and potentially a new way to treat everything from addiction to Alzheimer’s.

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"..But is that really a problem if you tolerate the drug well?"

Dunno bout that for anyone else.

I feel like my eating habits have changed drastically. Mostly just to do with quantities and frequency. I still eat fried foods and sweets. Just not so danged much of it. What used to be an appetizer or snack is now a "big meal".

I look at it like alcohol. I've already had "o-plenty" and know what I'm not missing. 😉😁

Plus, I just had a panniculectomy. The thighs and chest are next. So I don't wanna jack that investment.

I just came back from Tokyo. Stayed near the busiest train station in the world. The whole time I saw maybe three fat people.

Pretty clear the answer does not lie in bizarre new drugs.

23 posted on 05/19/2024 10:41:28 AM PDT by Red Badger (Homeless veterans camp in the streets while illegals are put up in 5 Star hotels....................)

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