Ozempic and suicidal thoughts?

 

EU Investigates Ozempic, Weight-Loss Drug Saxenda After Suicidal Thoughts Reported

By Ludwig Burger and Maggie Fick

July 11, 2023 

<

https://www.medscape.com/s/viewarticle/994162?ecd=WNL_trdalrt_pos1_230712_etid5632802&uac=149193PV&impID=5632802#vp_2>

(Reuters) - The European Medicines Agency (EMA) is investigating Novo Nordisk's diabetes drug Ozempic and weight-loss treatment Saxenda after Iceland's health regulator flagged three cases of patients thinking about suicide or self-harm.

Shares of the Danish drugmaker fell 1% on Monday following the news.

An EMA safety committee is looking into adverse events raised by the Icelandic Medicines Agency, including two cases of suicidal thoughts in those who used Ozempic, which contains the active ingredient semaglutide, and Saxenda, the regulator said.

Another patient on Saxenda, Novo's earlier and less effective weight-loss drug that contains the active ingredient liraglutide, reported thoughts of self-injury, the agency said.

Iceland's drugs regulator did not immediately respond to requests for details.

Novo Nordisk said patient safety was top priority and it treated all reports about adverse events very seriously. Its own safety monitoring so far found no "causal association" between the self-harming thoughts and the drugs, it said in a statement.

The EMA's investigation centres on medicines that contain either semaglutide or liraglutide. Novo's obesity treatment Wegovy, for which demand has surged in the United States, contains semaglutide.

The review was announced weeks after the regulator raised a thyroid cancer safety signal, a means to monitor potentially adverse effects, on several of Novo's products containing semaglutide.

Suicidal thoughts are not listed as a side effect in the EU product information for either drug.

In the United States, however, prescribing instructions for Wegovy recommend that patients are monitored for suicidal thoughts or behaviour.

According to the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) Public Dashboard, there have been at least 60 reports of suicidal ideation since 2018 from patients on semaglutide or their health care providers.

FAERS has received at least 70 such reports since 2010 from users of liraglutide or their health care providers.

Information in these reports has not been verified and the existence of a report is not proof of causation, the FDA says.

The FDA said it monitors safety of drugs throughout their life cycle. Wegovy's trials did not suggest increased risk of suicidal behavior, but the drug's label contains a warning for suicidal behavior and ideation because of risks associated with other weight management drugs, the regulator said.

SENSITIVE

Although Iceland's regulator has flagged only three cases, the issue of suicidal thoughts linked to weight-loss drugs is sensitive and has hobbled previous attempts by the drug industry to develop lucrative weight-loss drugs.

In clinical trials for Ozempic and Saxenda, Novo excluded people with a history of psychiatric disorders or recent suicidal behavior.

Sanofi's Acomplia, which never won U.S. approval, was withdrawn in Europe in 2008 after being linked to suicidal thoughts.

Acomplia was designed to modify parts of the nervous system that regulate appetite. New weight-loss drugs such as Wegovy regulate appetite by mimicking a gut hormone, and not directly interfering with brain chemistry.

Diet pills Contrave by Orexigen Therapeutics and Qsymia by Vivus Inc, approved in the U.S. in 2014 and 2012, respectively, carry warnings on their labels about increased risk of suicidal thoughts.

Markus Manns, senior portfolio manager at Union Investment and a Novo shareholder, said that a low incidence of suicidal thoughts might be acceptable for a drug against Type 2 diabetes but not for a weight-loss drug.

The EMA said on Monday it would consider whether the review should be extended to other medicines of the same class, known as GLP-1 receptor agonists.

The EMA's ongoing thyroid cancer investigation includes all GLP-1s.

Other drugs in the class include Eli Lilly and Co's Mounjaro. Lilly did not respond to a question from Reuters on whether the EMA had contacted them to provide data for the new investigation.

Penny Ward, a visiting professor in pharmaceutical medicine at Kings College in London and an expert on EU drug safety monitoring, said the most likely outcome of the investigation would be a change in the drug's label in the EU to carry a warning of the possible side effect of suicidal thoughts.

Another drug safety expert, who spoke on condition of anonymity, said the small size of Iceland's population might have led regulators to consider only a few adverse event cases were a significant proportion and worth investigating.

(Reporting by Ludwig Burger in Frankfurt and Maggie Fick in London; Additional reporting by Bhanvi Satija in Bengaluru, Michael Erman and Patrick Wingrove in New York, Robin Respaut in San Francisco, Louise Breusch Rasmussen in Copenhagen and Jennifer Rigby in London; Editing by Savio D'Souza, Nivedita Bhattacharjee, Sriraj Kalluvila and Barbara Lewis)

There are other alternative articles and podcasts regarding this remarkable drug...listen here:

https://drtyna.substack.com/p/episode107?utm_source=podcast-email%2Csubstack&publication_id=810381&post_id=137457686&utm_campaign=email-play-on-substack&utm_medium=email&r=2da2zn#details

POPULAR WEIGHT LOSS DRUGS AND THEIR GNARLY SIDE EFFECTS...

 

Popular Weight Loss Drugs Can Carry Some Gnarly Side Effects

Lindsay Kalter

June 13, 2023

Johnna Mendenall had never been "the skinny friend," she said, but the demands of motherhood – along with a sedentary desk job – made weight management even more difficult. Worried that family type 2 diabetes would catch up with her, she decided to start Wegovy shots for weight loss.

She was nervous about potential side effects. It took 5 days of staring at the Wegovy pen before she worked up the nerve for her first .25-milligram shot. And sure enough, the side effects came on strong.

"The nausea kicked in," she said. "When I increased my dose to 1 milligram, I spent the entire night from 10 p.m. to 5 a.m. vomiting. I almost quit that day."

Mendenall is among a growing number of people sharing personal stories online about the weight loss medication Wegovy – and similar drugs – delving into their sometimes unpleasant, and potentially gut-wrenching, side effects. 

While gastrointestinal (GI) symptoms seem to be the most common, a laundry list of others has been discussed in the news, on TikTok, and across online forums. Those include "Ozempic face," or the gaunt look some get after taking the medication, along with hair loss, anxiety, depression, and debilitating fatigue. 

Mendenall’s primary side effects have been vomiting, fatigue, and severe constipation, but she has also seen some positive changes: the "food noise," or the urge to eat when she isn’t hungry, is gone. Since her first dose 12 weeks ago, she has gone from 236 pounds to 215.

Warning Label

Wegovy’s active ingredient, semaglutide, mimics the role of a natural hormone called glucagon-like peptide, or GLP-1, which helps you feel well-fed. Semaglutide is used at a lower dose under the brand name Ozempic, which is approved for type 2 diabetes and used off-label for weight loss.  

Both Ozempic and Wegovy come with a warning label for potential side effects, the most common ones being nausea, diarrhea, stomach pain, and vomiting.

With the surging popularity of semaglutide, more people are getting prescriptions through telemedicine companies, forgoing more in-depth consultations, leading to more side effects, said Caroline Apovian, MD, a professor of medicine at Harvard Medical School and co-director of the Center for Weight Management and Wellness at Brigham and Women’s Hospital.

Specialists say starting with low doses and gradually increasing over time helps avoid side effects, but insurance companies often require a faster timeline to continue covering the medication, Apovian said. 

"Insurance companies are practicing medicine for us by demanding the patient go up in dosage [too quickly]," she explained. 

Mendenall’s insurance has paid for her Wegovy shots, but without that coverage, she said it would cost her $1,200 per month. 

There are similar medications on the market, like liraglutide, sold under the name Saxenda. But it is a daily, rather than a weekly, shot and also comes with side effects and has been shown to be less effective. In one clinical trial, the people being studied saw their average body weight over 68 weeks drop by 15.8% with semaglutide, and by 6.4% with liraglutide.

Tirzepatide, branded Mounjaro – a type 2 diabetes drug made by Eli Lilly that may soon gain FDA approval for weight loss – could have fewer side effects. In clinical trials, 44% of those taking semaglutide had nausea and 31% reported diarrhea, compared to 33% and 23% of those taking tirzepatide, although no trial has directly compared the two agents.

Loss of Bowel Control

For now, Wegovy and Saxenda are the only GLP-1 agonist shots authorized for weight loss, and their maker, Danish drug company Novo Nordisk, is facing its second shortage of Wegovy amid growing demand. 

Personal stories online about semaglutide range from overwhelmingly positive – just what some need to win a lifelong battle with obesity – to harsh scenarios with potentially long-term health consequences, and everything in between. 

One private community on Reddit is dedicated to a particularly unpleasant side effect: loss of bowel control while sleeping. Others have reported uncontrollable vomiting.

Kimberly Carew of Clearwater, FL, started on .5 milligrams of Ozempic last year after her rheumatologist and endocrinologist suggested it to treat her type 2 diabetes. She was told it came with the bonus of weight loss, which she was hoping would help with her joint and back pain. 

But after she increased the dose to 1 milligram, her GI symptoms, which started out mild, became unbearable. She couldn’t keep food down, and when she vomited, the food would often come up whole, she said. 

"One night I ate ramen before bed. And the next morning, it came out just as it went down," said Carew, 42, a registered mental health counseling intern. "I was getting severe heartburn and could not take a couple bites of food without getting nauseous."

She also had "sulfur burps," a side effect discussed by some Ozempic users, causing her to taste rotten egg sometimes.

She was diagnosed with gastroparesis, the weakening and paralysis of stomach muscle contractions that make it harder to digest food. Some types of gastroparesis can be resolved by discontinuing GLP-1 medications, as referenced in two case reports in the Journal of Investigative Medicine.  

Gut Hormone

GI symptoms are most common with semaglutide because the hormone it imitates, GLP-1, is secreted by cells in the stomach, small intestines, and pancreas, said Anne Peters, MD, director of the USC Clinical Diabetes Programs.

"This is the deal: The side effects are real because it's a gut hormone. It's increasing the level of something your body already has," she said. 

But, like Apovian, Peters said those side effects can likely be avoided if shots are started at the lowest doses and gradually adjusted up.

While the average starting dose is .25 milligrams, Peters said she often starts her patients on about an eighth of that – just "a whiff of a dose." 

"It'll take them months to get up to the starting dose, but what's the rush?" 

Peters said she also avoids giving diabetes patients the maximum dose, which is 2 milligrams per week for Ozempic (and 2.4 milligrams for Wegovy for weight loss). 

When asked about the drugs' side effects, Novo Nordisk responded that "GLP-1 receptor agonists are a well-established class of medicines, which have demonstrated long-term safety in clinical trials. The most common adverse reactions, as with all GLP-1 [agonists], are gastrointestinal related."

Is It the Drug or the Weight Loss?

Still, non-gastrointestinal side effects like hair loss, mood changes, and sunken facial features are reported among semaglutide users across the internet. While these cases are often what's known in the medical world as "anecdotal," which are personal, but not always easily verified clinical experiences, they can be very heartfelt.

Celina Horvath Myers, also known as CelinaSpookyBoo, a Canadian YouTuber who took Ozempic for type 2 diabetes, said she began having intense panic attacks and depression after starting the medication.

"Who I have been these last couple weeks, has probably been the scariest time of my life," she said on her YouTube channel. 

While severe depression and anxiety are not established side effects of the medication, some people get anhedonia, or the "reduced ability for pleasure," said W. Scott Butsch, MD, MSc, director of obesity medicine in the Bariatric and Metabolic Institute at Cleveland Clinic. But that could be a natural consequence of lower appetite, he said, given that food gives most people pleasure in the moment.

Many other reported changes come from the weight loss itself, not the medication, said Butsch.

"These are drugs that change the body’s weight regulatory system," he said. "When someone loses weight, you get the shrinking of the fat cells, as well as the atrophy of the muscles. This rapid weight loss may give the appearance of one’s face changing."

For some people, like Mendenall, the side effects are worth it. For others, like Carew, they’re intolerable.

Carew said she stopped the medication after about 7 months, and gradually worked up to eating solid foods again. 

"It’s the American way, we've all got to be thin and beautiful," she said. "But I feel like it's very unsafe because we just don’t know how seriously our bodies will react to these things in the long term. People see it as a quick fix, but it comes with risks."

Sources:

• Johnna Mendenall.
• Kimberly Carew, Clearwater, FL.
• Caroline Apovian, MD, professor of medicine, Harvard Medical School.
• Anne Peters, MD, director, USC Clinical Diabetes Programs.
• W. Scott Butsch, MD, MSc, director of obesity medicine, Bariatric and Metabolic Institute, Cleveland Clinic.
• Novo Nordisk.
• Health.harvard.edu.
• Reddit.com.
• Insider.com: "People on Ozempic for weight loss say they're pooping their pants and the bed.”
• Myclevelandclinic.org.
• Ozempic.com.
• Journal of Investigative Medicine High Impact Case Reports: "Medication-Induced Gastroparesis: A Case Report.”
• The Journal of the American Medical Association.
• YouTube: "The Dark Side of Ozempic – My Story," CelinaSpookyBoo.