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)

Why genetic Testing is about more than just your Ancestry...

 If you've heard about genetic testing in the past decade, it's probably been through the marketing of ancestry companies. There's the allure of finding out where you came from (or uncovering family secrets!), and at-home kits provided by these companies have shown everyday people how easy it is to test their DNA. 

But unfortunately, due to the popularity and widespread marketing of ancestry tests, most people aren't aware of the other benefits genetic testing can provide. While ancestry testing simply tells you where your family came from, genetic testing for health and wellness can lead you to a whole array of actionable insights into optimizing your eating, exercise, lifestyle choices, and more in order to achieve better health. 

As we’ve been utilizing genetic testing with our patients at Natural Health Haven LLC,  here are a few ways genetic testing can inform your health and wellness. 

  Personalized Care 

A lot of approaches to health and wellness these days focus on a one-size-fits-all approach, prescribing the same diet, exercise, and lifestyle choices to everyone. But everyone is unique — so shouldn't healthcare be tailored to that unique individual? Genetic testing uncovers a person's genetic variants, which give us insight into how that person’s cells and systems function, show the impact of the types of food you eat and the environment around you, and more. 

  Disease at the Root 

In addition to the one-size-fits-all approach to health, many times practitioners are helping their patients simply combat symptoms of chronic illness. But constantly treating symptoms can be timely and costly, and never really addresses the root issues anyway. Since genetic testing reveals how your body works at the cellular level, it can point towards the root causes of illnesses that are generating those symptoms. That way, diseases can be treated at the source. 

  Losing Weight 

Those who have struggled to lose weight may spend time, energy, and money seeking new ways to get healthy and lose weight when their genes are able to give them all the insight they need. Genes are able to give insight into what types of exercise are best for your body, whether it be more endurance exercises or power exercises. They can also show how your body stores fat, which nutrients it absorbs best to inform which foods to eat, and other insights that can form a more targeted recommendation plan. 

  Metabolism 

Your genes can also tell you more about your metabolism. We know that metabolism has a connection with energy and vibrancy, yet many of us have a "sluggish" metabolism we're not sure how to correct. Knowing your genes can give you insights into how your metabolism is affected by what you eat, how you burn energy, how you store fat, and more. 

  The Right Exercise 

What if you've been hitting the gym and trying to get fit, but you've been doing the wrong exercises all this time? Getting insights into your genes can actually show you whether your body is more suited for endurance activities, like running or bicycling, or whether your body is more suited for power activities like sprinting or weight lifting. Knowing more about how your body works means being able to choose the right activities for you. 

  Caffeine Intake 

We're all affected by caffeine in various ways — some people can drink coffee right up until bedtime, when others have to cut themselves off mid-morning! But do we know why? Our genes can tell us! Our genes are responsible for how quickly we metabolize caffeine, so we can know whether to have that extra cup or not. 

  Better Daily Choices 

As you can see, knowing your genes and how they affect your body can give you insights into many different aspects of your health and wellness so that you can make better choices each day about actions that affect you. For example, did you know that your genes can determine how well your body eliminates toxins, which can help you make choices about what environments to be in? Your genes can also give you insight into your stress levels, and flag if you're not getting enough sleep at night. 

   More Than Ancestry 

Knowing your genes can reveal a lot more to you than just what's stated above. Additionally, as our knowledge continues to increase around how genes work and how they impact our bodies, the blueprint that genetic testing provides for your optimal health will only become more detailed, allowing you to build the perfect life of health and wellness suitable to you. 

 Ready to start your personalized health journey?  

Let's talk..... Email us today at naturalhealthhaven@gmail.com

Need more information, here's a short video on the 3x4 genetic testing!

https://www.youtube.com/watch?v=b9VJ_0_n6-E

Artificial sweetener may not be what you desire if you're trying to lose weight....

 

Artificial Sweetener Ups Appetite in Women, People With Obesity

A new study (September 28, 2021), suggests that replacing sugar (sucrose) with the nonnutritive sweetener sucralose may not have the desired weight-loss effect, and in fact, it appears to increase appetite in women and people with obesity.

These are novel insights and further studies are needed, experts say.

After consuming a drink sweetened with sucralose versus sucrose, women and people with obesity had increased activity in the reward center of the brain and women ate more food at a post-fasting buffet.

"We were able to show that females and people with obesity may be more sensitive to artificial sweeteners," senior author Kathleen Page, MD, an associate professor of medicine at the Keck School of Medicine, University of Southern California, Los Angeles, summarized in a press release from the university.

"For these groups, drinking artificially sweetened drinks may trick the brain into feeling hungry, which may in turn result in more calories being consumed," she added.

Although many people use artificial sweeteners to try to lose weight, Page noted their place in a healthy diet is controversial. Some studies suggest they may be helpful, while others show they may contribute to weight gain, type 2 diabetes, and other metabolic disorders.

The new findings may partly explain these previous differences, she said.

The results also highlight the need to consider gender and body mass index in future research of nonnutritive sweeteners.

The study, by Alexandra G. Yunker, an MPH candidate in nutrition at Harvard University, Boston, Massachusetts, and colleagues, was published onlineSeptember 28 in JAMA Network Open.

Novel Findings, Need to Consider Sex, Adiposity in Future Research 

The current study "is of great importance as it provides novel insights into how adiposity and sex are associated with neural and behavioral outcomes of [nonnutritive sweetener] ingestion," Stephanie Kullmann, PhD, writes in an accompanying invited commentary.

Invited to comment, John L. Sievenpiper, MD, PhD, associate professor in the Department of Nutritional Sciences and Medicine at the University of Toronto, Ontario, Canada, agreed that the data need to be reproduced.

Several questions remain, he stressed in an email to Medscape Medical News: "Was it the sucralose per se or the absence of calories that explains these findings? And the bigger question is, do these differences by adiposity and sex translate into weight gain?"

Systematic reviews and meta-analyses of the available randomized controlled trials of low and no calorie sweeteners including sucralose show the expected decrease in caloric intake and downstream weight loss in both males and females who are overweight or obese, he noted.

"It would be useful to understand if there are important interactions by adiposity and sex in future trials," Sievenpiper added.

Young Men and Women of Diverse Weight

Nonnutritive sweeteners are now used by more than 40% of US adults, the researchers write, but studies have reported mixed results on appetite, glucose metabolism, and body weight, and it is not clear whether these sweeteners are beneficial or harmful to health.

Prior research that was mainly in men and lean participants showed that brain areas involved in the regulation of taste, reward, and homeostasis may respond differently to nonnutritive versus nutritive sugars.

The researchers aimed to investigate this using initial data from the Brain Response to Sugar study (clinicaltrials.gov).  

They analyzed data from 74 healthy 18- to 35-year-olds (58% women) with a mean age of 23. Overall, 37% had a healthy weight, 32% were overweight, and 31% had obesity.

Participants made three separate visits to the study center after a 12-hour overnight fast.

At each visit they drank 300 mL of water, a sucralose-sweetened drink, or a sucrose-sweetened drink.

They had blood drawn at baseline and at 10, 35, and 120 minutes after ingesting the drink.

At 20 minutes after consuming the drink, they had a functional MRI, during which they were shown 12 pictures of high-calorie, low-calorie, sweet, or savory foods and four pictures that were not foods and were asked to rank their appetite.

At 125 minutes after they ingested the drink, participants had access to a buffet meal.

"As expected, endocrine responses" — blood levels of glucose, insulin, and glucagon-like peptide-1 — "were greater after sucrose than sucralose ingestion," Kullmann noted, "but there were no significant differences based on sex and adiposity."  

However, "the most prominent and novel findings were observed on a neurobehavioral level," according to Kullmann.

That is, individuals with obesity (but not those with overweight or a healthy weight), had greater neural activity in the prefrontal reward-related areas of the brain, in response to savory food images, after ingesting a drink containing sucralose versus sucrose.

Similarly, after consuming a sucralose-sweetened drink as opposed to a sucrose-sweetened drink, female participants had greater activity in reward areas of the brain in response to food cues, especially high-calorie and sweet foods.

Women also consumed more calories at the buffet meal after they had ingested a sucralose-sweetened drink than after a sucrose-sweetened drink.

The study was supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH). The Research Electronic Data Capture (REDCap) database used is supported by the Southern California Clinical and Translational Science Institute through an NIH grant. The researchers and editorialist have reported no relevant financial relationships.

JAMA Netw Open. 2021;4:e2126313, e2128047. Article, Editorial