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Medscape
7 days ago
- Health
- Medscape
In Real World, Women More Likely to Have Issues With GLP-1s
If it weren't for post hoc analyses and findings from curious academic labs, the substantial list of biological differences that separates the sexes would still be relegated to the shadows. That list — including research from the fields of neurology, cardiology, immunology, oncology, endocrinology — shows that the longtime presumption of men and women reacting as one to diagnoses, disease progression, and treatment should be considered, scientifically speaking, passé. But in the world of clinical trials, it has been and still is mostly a sexless, homogenous world. One reason: Stratifying by sex in a trial would not be cheap. 'Doing that up front would cost millions more,' said Antonella Santuccione Chadha, MD, PhD, founder and CEO of the Women's Brain Foundation and a former member of the EU Commission Directorate-General for Health and Food Safety. A significant issue is under enrollment of women in randomized trials, meaning the percentage of women enrolled isn't in line with the percentage of women with a particular disease in the real world — so signals that indicate an adverse event are not picked up. From a systems perspective, women do not clear drugs through their kidneys as quickly as men, and women maintain a higher blood concentration of the medication. 'Women may be overmedicated,' Neurologist Irving Zucker and others wrote in a 2020 analysis of 86 medications. This can lead to adverse events (AEs). And they do. ' Women experience adverse drug reactions nearly twice as often as men, yet the role of sex as a biological factor in the generation of [these reactions] is poorly understood,' Zucker wrote in that study, published in the journal Biology of Sex Differences , which showed that pharmacokinetics 'strongly linked' sex differences in adverse drug events. Antonella Santuccione Chadha, MD, PhD Among the 86 medications was the GLP-1 receptor agonist (GLP-1 RA), liraglutide. It was found to be biased toward women with regard to headache, vomiting, nausea. There are little stratified data in the GLP-1 RA receptor clinical trials, let alone appropriate enrollment percentages, as compared to real world disease prevalence. Considering that these medications are being used in patients with diabetes, obesity and overweight, cardiovascular problems, and likely in the future, to mitigate Alzheimer disease advancement, it likely would help to know how sex affects these drugs. So the question is: How can general practitioners determine what treatment is right for patients, especially their female patients, when so little evidence is based on sex? 'The side effects are very real and important to track,' said Sadiya S. Khan, MD, MSc, professor of cardiovascular epidemiology, and associate professor, medicine medical social sciences, preventive medicine, at the Feinberg School of Medicine at Northwestern University, Chicago. 'The truth about GLP-1 agonists is that you have to personalize it for the patient in front of you,' said Martha Gulati, MD, MS, professor of cardiology at Cedars-Sinai Heart Institute. Efficacy has to be balanced with the potential for side effects. 'Every individual will be slightly different.' Sex Differences of Note In its natural state, GLP-1 is found in many areas of the body, including the brain. It has multiple purposes, including gastric emptying, food intake inhibition, and neuroprotective effects on lung and cardiovascular systems. But in its natural state, GLP-1 has a short half-life, hence the pharmaceutical drive for analogues. As a class, these analogues, primarily the injectables, have been much ballyhooed for their ability to treat diabetes, induce weight loss, and reduce the risk for cardiovascular events. One recent study also demonstrated how the GLP-1 RAs can mitigate cognition issues. These analyses show how the GLP-1 RAs work at the stratified population level: In this study, women, who generally have a smaller stature than men, had higher concentrations (32%) of the tested medication than men; patients with diabetes had lower amounts of medication than those with normal blood glucose levels or prediabetes. In a new analysis of FAERS, the FDA's adverse event reporting system, among reports of neurologic related events in GLP-1 agonists, 46.25% occurred within 30 days of the start of treatment. The report, based on complaints filed from 2004 to 2025, found that 11.58% of the 250,014 listed were neurologic in nature. Women reported 65% of the 28,953 neurologic AEs events; most came from consumers. The top AEs reported were dizziness, tremor, and dysgeusia. Women who had taken semaglutide, liraglutide, and tirzepatide reported 65% of the 372 psychiatric events found in the EudraVigilance database, between January 1, 2021, and May 30, 2023. In a new JAMA article discussing the management of GLP-1 events, neurologic issues are not mentioned, just common gastrointestinal ailments, including nausea. In the huge study published in February confirming semaglutide 2.4 mg safety in overweight, obesity, cardiovascular disease but not diabetes, the sexes were segregated in listing fractures, poisoning, and procedural events but not in serious cardiac and nervous system disorders. article discussing the management of GLP-1 events, neurologic issues are not mentioned, just common gastrointestinal ailments, including nausea. In the huge study published in February confirming semaglutide 2.4 mg safety in overweight, obesity, cardiovascular disease but not diabetes, the sexes were segregated in listing fractures, poisoning, and procedural events but not in serious cardiac and nervous system disorders. The inclusion criteria for the still-running Evoke trials, which is testing oral semaglutide's efficacy in early-stage symptomatic Alzheimer's disease (AD), have no breakdown of the 1840 participants by sex, either in or the peer-reviewed summary. AD affects women significantly more than men. Efforts to reach an investigator were not successful. With regard to diabetes, it seems the sexes have more differences than commonalities, according to a 2023 study in Diabetologia , the journal of the European Association for the study of diabetes. One review found men: are younger at diagnosis; have a lower BMI and a lower risk factor burden, including hypertension and more weight gain; have a lower relative risk for cardiovascular complications and death; and get guideline recommended care more than women. Sadiya S. Khan, MD, MSc 'Across their lifetime, changes in sex hormones mean that women experience greater variations in the risk of cardiometabolic disease, including type 2 diabetes,' the Austria-based authors wrote. A Danish study reviewing more than 200,000 cases in the country's national registry reached similar conclusions. A cause for concern: Population trends show that more women are obese or severely obese, particularly among those older than 60 years. Clinical Discussion Prescribing women GLP-1 RAs takes some planning, Gulati and Khan said. Conversations about what to expect are critical, especially about potential AEs. Gulati said women respond better to these medications, especially if they are premenopausal. These physicians, both preventive cardiologists, discuss the benefits, including lower hypertension, weight reduction, and better glycemic control. Advice includes eating small meals, avoiding greasy food, and eating lots of fiber because constipation is no fun. And patients have to be prepared for the side effects. 'I have this oatmeal spiel,' Gulati said. One patient, she said, insisted on eating greasy food until the AEs won out. 'She started improving her diet and she got the results she wanted…If they get something you told them about, they know more.' Gulati, president-elect of the American Society for Preventive Cardiology, said some women won't be able to go up to the highest dosage because of the AEs. Khan said the AEs increase as the GLP-1 RA dosage increases. She said that in real life, 80% of people taking a GLP-1 RA stop because of the side effects. 'It's about going slow and seeing if people can benefit.' At least one premarketing clinical study claimed that dose adjustment by sex wasn't necessary. Robert Kushner, MD, the lead investigator on the semaglutide obesity study, said in a JAMA podcast that more than 30% of patients, at least in the phase 3 trials, stopped using semaglutide because of nausea, constipation, diarrhea, and vomiting. His advice paired with that of Khan and Gulati. Most, if not all, of this conversation could be avoided if sex-based evidence was generated in preclinical research and then used to shape the trial, said Santuccione Chadha. By investing more money in the beginning of the trial to determine sex-based differences, there would be a 'higher return on investment across the chain.' There would be fewer side effects and more adherence to drugs, the GLP-1s included. But with the current method of research, 'What happens is that there are unexpected side effects, more adverse events in the female population, who also get more serious events.' Gulati agreed more planning is needed prior to trial enrollment. 'Honestly? I think it is because of a lack of prestudy planning. Who do we want, and where will we get them?' If the trial is underpowered, 'you can't look at sex differences.' The fact that the GLP-1 RAs have proven effective in so many body systems now has more specialists prescribing these medicines. Khan said interdisciplinary care is critical, so it's necessary to have a point person. 'We are realizing this, who is owning responsibility, who is comfortable with it.'
The Herald Scotland
19-07-2025
- Sport
- The Herald Scotland
WNBA needs to pay players before it gets ugly, just ask U.S. Soccer
The players and the WNBA had their first face-to-face meeting in months Thursday during All-Star weekend. To say it was lacking in substance is an understatement. "Wasted opportunity," "disrespectful" and "frustration" were words used by players to describe it. It did serve one purpose, however. With 40 players showing up -- veterans and rookies, megastars and role players, the largest gathering outside the Wubble -- it sent an unmistakable message to the league about their commitment. "I hope it expedites the process so we're not going back and forth where they're trying to test us and see who flinches first. Because we're not going to," Minnesota Lynx forward Napheesa Collier, a WNBPA vice president as well as this season's favorite for MVP, said Friday. "We are always going to stand firm. Hopefully they just realize that earlier, so that we're not wasting time over things that we're not moving on." The W, like U.S. Soccer, seems to think players should be grateful just to be playing. That the money the NBA and some of its owners pumped into the league entitles them to gouge the players in perpetuity. Funny how this is never an issue with men's teams, even the ones that are perennial money losers. The W didn't respond to the players Friday. But on Thursday night, league commissioner Cathy Engelbert told The Associated Press the talks are "a process." "We're both in listening mode," Engelbert told the AP. "We're going back and forth on issues. We know what's important to players. We know what's important to owners and striking the right balance." Does the W really, though? Because it's been nine months since the players opted out of the existing contract and five months since the players sent the league ideas for salary increases and pay structure. To show up Thursday unprepared or unwilling to negotiate is not the move of a league that understands the urgency and gravity of the moment. "It was pretty shocking to see," New York Liberty forward Breanna Stewart, also a union vice president, said. "Not many things did we both agree on. I think there were two bullet points where we were like, `OK, we can move forward with this.'" But this is what happens when women aren't taken seriously. When the U.S. women's national team sued U.S. Soccer for equal pay in 2019, three months before the World Cup, the federation failed to appreciate how determined the players were. This despite the fact the players had taken the drastic step of suing their employer, and every single member of the team had signed onto the lawsuit. The federation assumed, wrongly, that the women would eventually give in, preferring to get something rather than holding out for everything they deserved. They didn't realize how knowledgeable the players and their advisers were about the economics. U.S. Soccer's biggest miscalculation, however, was not recognizing the public support for the players. When fans serenaded the USWNT with chants of "Equal pay! Equal pay!" after they won the World Cup in France, it was a resounding rebuke to U.S. Soccer and everyone else who short-changed women. Sound familiar? This is a time of explosive growth for the WNBA. A monster media rights deal that will pay the league $200 million a year, more than triple what it gets now, begins next year. Franchise valuations are soaring, with the expansion Golden State Valkyries recently valued at $500 million and five other teams worth $250 million or more, according to Sportico. Sponsors are clamoring for any piece of the action they can get. None of this is a secret. Nor is it a secret that W players are woefully undercompensated. Player salaries top out at $250,000 and revenue "sharing" is around 10%, compared to the 50% that is typical of almost every professional men's league. The players, rightfully, want more. They know they deserve more. And, like the USWNT in 2019, they're no longer willing to accept less. "We're not just players that run up and down the court and do amazing things. Some of us are business owners, some of us are foundation owners. So we know what it takes," said Las Vegas Aces center A'ja Wilson, who, coincidentally, was wearing the latest version of her signature shoe released for the All-Star Game. "When we see the revenue, when we see things flowing into our league, we want that. We are going to demand that because we see it and we see the growth," Wilson said. "And when you see a business growing, obviously the people that are working for the business should have some say in that as well. So I think we know what we are talking about for sure." The public knows, too. Aside from the Neanderthals who parrot that misleading narrative of the W being propped up by the NBA, fans are going to be on the side of Caitlin Clark, Paige Bueckers, Wilson and Collier rather than rich owners and league officials. So, too, will the sponsors. And when that happens, the league might regret its choices. "We as players know what we're worth. The fans know what we're worth," said Nneka Ogwumike, the longtime union president. "Now we need the league to know what we're worth." The WNBA and its players will eventually come to an agreement. The league has a choice: Be seen as an equal partner that wanted to do right by the players or as an overlord that had to be dragged kicking and screaming into doing the right thing. It might want to ask U.S. Soccer which one is better. Follow USA TODAY Sports columnist Nancy Armour on social media @nrarmour.
Forbes
11-07-2025
- Entertainment
- Forbes
Today's ‘Quordle' Hints And Answers For Saturday, July 12
Here's some help with today's Quordle, including hints and the answers. Before today's Quordle hints and answers, here's where you can find the ones for Friday's game: Hey, folks! Hints and the answers for today's Quordle words are just ahead. How To Play Quordle For any newcomers joining us, here's how to play Quordle: Just start typing in words. You have four five-letter words to guess and nine attempts to find them all. The catch is that you play all four words simultaneously. If you get a letter in the right place for any of the four words, it will light up in green. If a word contains a letter from one of your guesses but it's in the wrong place, it will appear in yellow. You could always check out the practice games before taking on the daily puzzle. Here are some hints for today's Quordle game, followed by the answers: What Are Today's Quordle Hints? FEATURED | Frase ByForbes™ Unscramble The Anagram To Reveal The Phrase Pinpoint By Linkedin Guess The Category Queens By Linkedin Crown Each Region Crossclimb By Linkedin Unlock A Trivia Ladder What Are Today's Quordle Answers? Spoiler alert! Don't scroll any further down the page until you're ready to find out today's Quordle answers. This is your final warning! Today's words are... That's all there is to it for today's Quordle clues and answers. Be sure to check my blog for hints and the solution for Sunday's game if you need them. See you then! If you'd like to chat about Quordle and New York Times word games such as Wordle, Connections and Strands (and to hang out with a bunch of lovely people), join us over at Discord! Also, subscribe to my newsletter, Pastimes!
Scottish Sun
05-06-2025
- Sport
- Scottish Sun
Jack Grealish appears to take swipe at Pep Guardiola as he's set to be snubbed from Man City's Club World Cup squad
GUARD UP Jack Grealish appears to take swipe at Pep Guardiola as he's set to be snubbed from Man City's Club World Cup squad Click to share on X/Twitter (Opens in new window) Click to share on Facebook (Opens in new window) JACK GREALISH has appeared to take a swipe at boss Pep Guardiola's selection policy. The Manchester City star, 29, has fallen out of favour at the Etihad. Sign up for Scottish Sun newsletter Sign up 4 Jack Grealish has fallen out of favour under Pep Guardiola Credit: Reuters Grealish started just seven Premier League matches during the 2024-25 season. Having made just one brief cameo in the final six games of the campaign, Grealish was left on the bench during the FA Cup final - with Guardiola instead turning to teenage debutant Claudio Echeverri as his side chased an equaliser. Appearing on talkSPORT, Grealish's former Aston Villa team-mate Gabriel Agbonlahor criticised Guardiola's treatment of his pal. Agbonlahor said: "I think towards the end of the season, it felt to me like it got a bit personal. READ MORE IN FOOTBALL 'STARSTRUCK' Grealish poses with unrecognisable Prem icon and calls him his 'boyhood hero' "Bringing on a young kid for his debut in an FA Cup final when you're chasing a goal, when you've got someone who's had the career Jack's had just seemed a bit odd. "That seemed a bit personal to me, like a last little dig to get you out, to upset you, to (make) you want to move. But we've seen this before from Pep. "Pep can be ruthless at times. If he feels that you're not part of his future plans, he will get rid of you." When talkSPORT posted the clip to Instagram, Grealish commented, appearing to point to how many sub appearances he's made: "What u want me to do score a hatty in 20?" The post received several other comments, including one that read: "Dude jack is been bad lately and I'm not surprised Pep did that." BEST ONLINE CASINOS - TOP SITES IN THE UK 4 Grealish replied to a talkSPORT post Credit: Instagram @talksport 4 The Man City star also responded to a fan Credit: Instagram @talksport Grealish responded: "haha I've been bad lately? "Scored 3 goals in my last 3 appearances over 45 mins but okie dokie love x". Jack Grealish to Napoli?! Conte Plots Shock £100M Raid – Would City Really Let Him Go? Grealish scored one goal and laid on one assist in 20 Prem appearances during the 2024-25 season. His three goals in all competitions came against Leicester, Paris Saint-Germain and Salford. Yesterday it emerged that Grealish will not head to the US with his team-mates for the Club World Cup, as he nears a City exit. The England ace is said to be attracting interest from the Premier League and overseas - with Villa, Newcastle, Everton and Napoli among the interested suitors. Boss Guardiola said in May: 'Of course Jack has to play. He needs to do it — with us or another place.' SunSport recently revealed that Grealish had accepted that he may need to leave City in order to reclaim his England place in time for the World Cup. 'I LOVE JACK GREALISH' Having missed out on last summer's European Championships, Grealish has been left out of both of Thomas Tuchel's squads so far as Three Lions boss. Asked about the 39-cap star in March, the German said: "I love Jack Grealish. I love everything about him; his personality, his quality. "The guy has courage, can take the heat, not afraid of the Bernabeu whistles when he's on the ball, it does not affect him, it affects him only in the best way. "Is he a player who should be available and have an impact in our (England) squad? Yes, 100 per cent. But lately, he simply has no rhythm and he and I agree 100 per cent. "He said, 'Thomas, I'm not a start-stop player. It's so hard for me to influence a match from the bench and be on the bench again, and two weeks later start again'. "I'm not judging anyone, but it's just a characteristic of Jack, he gets better with every minute. The more he plays the better he gets and then he becomes a proper machine."
Independent Singapore
23-04-2025
- Sport
- Independent Singapore
Know the athletes who won the Laureus World Sports Awards
The Laureus Awards ceremony was recently held in Madrid, and here are the athletes who were honoured for their exceptional performances in sports. Simone Biles was named Sportswoman of the Year, and the Swedish pole-vaulter Mondo Duplantis was honoured as the Sportsman of the Year. American gymnast Biles earned this recognition after an incredible performance at the 2024 Paris Olympics, where she made a powerful comeback. In the prestigious competition, she won gold medals in the team event, the all-around, and the vault, along with a silver medal in the floor exercise. This success came after her three-year hiatus, when she withdrew from the Tokyo Olympics to focus on her mental health. This is the fourth time she has received the Laureus award. She now has the same number of awards as her fellow American and tennis legend, Serena Williams. Biles shared, 'I'm so happy to be here in Madrid and to receive my fourth Laureus Award… I won this Award for the first time in 2017, and Laureus has been a part of my story since then. There might be a little girl watching someone like me on television and deciding she can do it, too.' Meanwhile, Mondo Duplantis received the Laureus Sportsman of the Year for the first time after being nominated for the past three years. It was handed to him by last year's winner, tennis star Novak Djokovic. Duplantis made history by being the second track-and-field athlete to win the award, following sprinting legend Usain Bolt. At the 2024 Paris Olympics, Duplantis won his second Olympic gold medal and broke his own world record for the ninth time. A month later, he broke the record again at the Silesia Diamond League event. Duplantis joked, 'I am incredibly honoured to have won my first Laureus, this is the ultimate award that we athletes want to win. I know because this is the fourth time I have been nominated –and that proves it's harder to win a Laureus than an Olympic gold medal.' Brazilian gymnast Rebeca Andrade was also honoured with the Comeback of the Year award. She earned the award after making an incredible return to top-level competition at the 2024 Paris Olympics, where she won a gold medal in the floor exercise and beat Simone Biles. Her journey as an athlete is inspiring because she battled through serious injuries that once threatened to end her career. Overcoming setbacks, her performance in Paris showed not only her talent but also her determination and resilience to keep doing what she is passionate about. Teenage football star Lamine Yamal won the Breakthrough of the Year award. The athlete played a key role in helping Spain win the European Championship last year. He is now the sixth footballer to win this award. Retired tennis star Rafael Nadal received the Laureus Sporting Icon award for his legendary contribution to the sport. The French Open will also pay tribute to Nadal on the opening day of the tournament. Here are the athletes who won the Laureus World Sports Awards this year: Simone Biles – World Sportswoman of the Year Mondo Duplantis – World Sportsman of the Year Real Madrid – World Team of the Year Lamine Yamal – World Breakthrough of the Year Rebeca Andrade – World Comeback of the Year Jiang Yuyan – World Sportsperson of the Year with a Disability Tom Pidcock – World Action Sportsperson of the Year Kick4Life – Laureus Sport for Good Rafael Nadal – Laureus Sporting Icon Kelly Slater – Laureus Lifetime Achievement
