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Team Metabolic Health

The meteoric rise of Denmark’s Novo Nordisk A/S from century-old insulin producer to Europe’s most valuable company has been a feel-good story of innovation in a region where those are rare. Its diabetes and obesity drugs Ozempic and Wegovy, have become a global phenomenon: They opened up a market potentially worth $100 billion and transformed the Danish economy (and Hollywood too). It’s reminiscent of Finland’s boom in the heyday of cellphone pioneer Nokia Oyj — until Apple Inc.’s iPhone spoiled the party.
Nokia-esque turn for the worse is now potentially unfolding, however. Novo’s shares plummeted by 21% on Friday to their lowest level since August 2023, after the study results of next-generation experimental obesity shot CagriSema fell short of the 25% weight loss that had been predicted. The actual result of 20.4% to 22.7% weight loss over 68 weeks is obviously neither failure nor disruption, as my colleague Lisa Jarvis notes, and is in line with the performance of rival Eli Lilly & Co.’s existing Zepbound shot. But it does speak to the eroding competitive advantage of a European first mover in the face of a ferocious US rival: Lilly’s shares rose and it’s now viewed as the preeminent market player that could become the first trillion-dollar drug company.

Credit: Bloomberg

There were signs that Novo might find itself in a less comfortable spot than that suggested by its premium valuation. Despite effectively arriving late to the party, Lilly’s Zepbound has built a roughly 40% market share in the US — the weight-loss El Dorado — in less than a year. And even if supply constraints are the bigger story in a market where there’s plenty of demand to go around, developments like the results of a head-to-head trial of Zepbound and Novo’s Wegovy — which Lilly said gave a slight advantage to Zepbound — added to the sense of a marketing balance slowly tipping away from the Danish company. The above chart shows how Novo’s market value has been lagging Lilly’s for the past year.

There’s likely to be more trans-Atlantic pressure ahead. Lilly is looking at whether an experimental compound called retatrutide can change the game after it delivered 24% weight loss in a smaller study last year. Other drugmakers, like Amgen Inc. and Pfizer Inc., are eyeing their own tilt at the market, and the patent expiration of Wegovy in the early 2030s is also on the horizon. Bloomberg Intelligence’s John Murphy notes some of these developments will likely challenge consensus expectations of Wegovy driving almost 20% of Novo’s sales in 2030.

From a pharma perspective, this is all good news for the consumer; yet it’s a pretty humbling development for Europe and its mega-cap “GRANOLAS” — an acronym devised by Goldman Sachs Group Inc. capturing top companies with a competitive advantage, including chip-equipment supplier ASML Holding NV, LVMH Moët Hennessy Louis Vuitton SE and Novo. The economic spillover of Novo’s boom has been big: a hiring binge employing 32,000 people in Denmark, the opening of new manufacturing sites and investments in countries like France and an export boost moving the needle of European gross domestic product. Some of that is at risk, with Novo’s selloff on Friday seen weighing on the Danish currency. Still, as Nordea’s Helge Pedersen notes, the Danish economy is still well-diversified — it would be wrong to imagine the kind of downturn that Finland went through as Nokia shriveled.

Europe’s corporate giants are facing plenty of challenges going into 2025, from a luxury slowdown and Trump tariffs to a domestic market that’s so sluggish it’s in danger of “disappearing,” as hedge fund boss Ken Griffin recently put it. While Novo is still a success story — and remains Europe’s most valuable firm — the home-market advantage of the US and the competitive pressure of its firms is a pattern that investors have to keep in mind all over again. Europe has to hope there’s a different ending this time.

Credit: The Economic Times

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С каждым днем появляются десятки новых онлайн казино, которые предлагают гемблерам огромные возможности и большой каталог азартных развлечений на любой вкус. Конечно, каждый игрок вправе самостоятельно подобрать интересующее его игровое заведение, однако в таком случае следует учитывать все возможные риски, связанные с его надежностью.

Чтобы не ошибиться в выборе, лучше всего ориентироваться на рейтинг казино онлайн. Он составляется ведущими экспертами и опытными аналитиками, которые при этом анализируют огромный объем информации. Во время составления рейтингов casino online они учитывают многие факторы (честность, надежность, легальность, ассортимент игр, разнообразие бонусов), ориентируются на отзывы реальных игроков, самостоятельно проверяют интересующие интернет-клубы. Только после тщательных проверок составляются списки лучших онлайн казино, в которых можно играть без лишних опасений и получать при этом гарантированные выигрыши в случае успеха.

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Пытаясь самостоятельно выбрать казино онлайн с выводом для приятного проведения времени, игроки нередко попадают на скриптовые казино, на официальных сайтах которых крайне не рекомендуется играть на реальные деньги. Чтобы избежать столь неприятных последствий, пользователям рекомендуется обращать внимание на рейтинг казино онлайн на деньги, составленный компетентными в этом вопросе людьми. Согласно оценкам квалифицированных специалистов, в ТОП лучших онлайн казино вошли:

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1

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4

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6

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8

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9

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10

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“Год запуска”: “2016”,

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“Год запуска”: “2018”,

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“Средний RTP для игровых автоматов”: “98,6%”,

“Год запуска”: “2018”,

“Скорость вывода”: “0-48 часов”

“Место в рейтинге”: “5”,

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“Средний RTP для игровых автоматов”: “98,5%”,

“Год запуска”: “2012”,

“Скорость вывода”: “0-24 часа”

“Место в рейтинге”: “6”,

“Название казино”: “Riobet”,

“Средний RTP для игровых автоматов”: “97,9%”,

“Год запуска”: “2014”,

“Скорость вывода”: “Моментально”

“Место в рейтинге”: “7”,

“Название казино”: “Pin Up”,

“Средний RTP для игровых автоматов”: “97,8%”,

“Год запуска”: “2018”,

“Скорость вывода”: “До 60 минут”

“Место в рейтинге”: “8”,

“Название казино”: “Volna”,

“Средний RTP для игровых автоматов”: “97,3%”,

“Год запуска”: “2022”,

“Скорость вывода”: “1-24 часа”

“Место в рейтинге”: “9”,

“Название казино”: “Selector”,

“Средний RTP для игровых автоматов”: “97,1%”,

“Год запуска”: “2016”,

“Скорость вывода”: “До шести часов”

“Место в рейтинге”: “10”,

“Название казино”: “Play Fortuna”,

“Средний RTP для игровых автоматов”: “96,08%”,

“Год запуска”: “2012”,

“Скорость вывода”: “Моментально”

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Team Metabolic Health

Eli Lilly (LLY.N) has said its weight-loss drug helped nearly 99% of patients remain diabetes-free after three years of weekly injections.

The results suggest that tirzepatide – the active ingredient in Lilly’s diabetes drug Mounjaro and weight-loss treatment Zepbound – could prevent one new case of diabetes for every nine patients treated.

The company initially disclosed the trial results in August.

The detailed data, published in The New England Journal of Medicine on Wednesday, showed an association of the drug with improvements in blood glucose levels, cardiometabolic risk factors, and health-related quality of life, which sustained over three years.

The late-stage trial, which enrolled 1,032 adults with prediabetes and obesity, demonstrated a 94% reduction in the risk of progression to type 2 diabetes compared to placebo.

Patients treated with weekly injections showed an average weight reduction of up to 22.9%, maintained for over three years.

“These results are impressive given the degree of sustained weight reduction and decrease in risk of diabetes,” said Ania Jastreboff, director of the Yale Obesity Research Center.

Eli Lilly and rival Novo Nordisk have been testing their drugs for conditions beyond obesity and diabetes.

The U.S. Food and Drug Administration is set to decide on the use of Lilly’s weight-loss drug to treat moderate-to-severe obstructive sleep apnea.

The company plans to submit data on heart failure with preserved ejection fraction and obesity to the U.S. FDA and other global regulatory agencies later this year.

Credit: Reuters

Team Metabolic Health

Understanding glucagon: The counterpart to insulin

GLP-1 and GIP regulate blood sugar after meals by stimulating insulin secretion in a glucose-dependent fashion. They also suppress glucagon release, delay gastric emptying, and suppress appetite centrally, reducing food intake. 

Glucagon is a peptide hormone secreted primarily from the alpha cells of the pancreatic islets of Langerhans. Minor amounts are also produced in the L cells of the intestine and certain neurons of the brainstem and hypothalamus. The basal secretion of glucagon stabilizes blood glucose levels, counterbalancing the basal secretion of insulin.

Glucagon stimulates the liver to produce more glucose, thus maintaining glucose homeostasis. It balances the action of insulin, which is secreted from the pancreatic islet beta cells in response to hyperglycemia.

In the pancreas, the enzyme prohormone convertase (PC) 2 processes the prohormone proglucagon to glucagon. In the intestine and brain, PC1 converts proglucagon to the incretin hormones, glucagon-like peptide 1 (GLP-1) and glucagon-like peptide 2 (GLP-2).

The effect is to stimulate the hepatic breakdown of the complex carbohydrate glycogen to glucose (glycogenolysis), synthesis of glucose (gluconeogenesis), suppression of glycolysis (the anaerobic breakdown of glucose), and inhibition of glycogenesis (the formation of glycogen). This increases blood glucose levels.1,2

When energy is scarce or in high demand, glucagon breaks down lipids and proteins to substrates that can be used to generate energy, simultaneously reducing the appetite and stimulating energy expenditure. It also suppresses lipid synthesis in the liver.1,2

The most potent stimuli for glucagon secretion are hypoglycemia, prolonged fasting, exercise, and after a protein-rich meal. Glucagon levels in the blood may rise 3-4-fold with hypoglycemia or during exercise, and it is a lifesaving homeostatic hormone in severe hypoglycemia.

In prolonged fasting, glucagon primarily stimulates gluconeogenesis. It also ensures adequate glucose supply to the brain and exercising muscle during physical activity.

The role of glucagon in diabetes

Glucagon as a hyperglycemic hormone was first described in 1922 by Kimball and Murlin, who termed it the glucose agonist (later shortened to glucagon). 1,2

Glucagon was initially used to treat insulin-induced hypoglycemia, often encountered in unstable diabetes, because of its ability to induce almost instantaneous rise in blood glucose levels.

Hypoglycemia significantly impairs the health, survival, and quality of life in diabetes mellitus. Yet glucagon remains underused, despite being “the only first-line treatment for severe hypoglycemia that can be administered in a nonmedical environment”.5

Glucagon-Like Peptide-1 (GLP-1): A key player in diabetes management

Type 2 diabetes mellitus (T2DM) is associated with hyperglycemia. However, glucagon levels remain high in fasting and postprandial states. Interestingly, this is not suppressed by oral glucose intake but responds readily to intravenous glucose. This suggests the involvement of gut incretins like the glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 in diabetic hyperglucagonemia.

Semaglutide and Type 2 Diabetes: Efficacy, Safety, and Outcomes

GLP-1 and GIP regulate blood sugar after meals by stimulating insulin secretion in a glucose-dependent fashion. They also suppress glucagon release, delay gastric emptying, and suppress appetite centrally, reducing food intake. 

Aberrant glucagon responses promoting hyperglycemia may be due to the impaired regulation of glucagon and insulin secretion, as well as disrupted alpha cell responses to insulin.

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Extrapancreatic glucagon-like peptides may also play a role, opening the way for glucagon receptor antagonist in T2DM therapy. 

GLP-1 receptor agonists (GLP-1 RAs) are synthetic GLP-1 analogs that resist natural degradation and thus have a long half-life. They include semaglutide, exenatide, dulaglutide and liraglutide. They lower blood glucose levels without inducing hypoglycemia, and are primarily used to treat T2DM.  

Newer GLP-1 RAs have greater homology with human GLP-1. Some require only weekly use by injection, and a few are oral formulations.

The future of glucagon therapy

Alternative treatments for type 1 diabetes mellitus that have been investigated include whole-pancreas and pancreatic islet transplantation, stem cell transplants, gene transfer or growth factor treatments to help non-islet cells transform into beta cells, and immunization to prevent the formation of beta-cell antibodies.

Peroxisome proliferator-activated receptors (PPARs), G protein-coupled receptor 119 (GPR119) agonists, interleukin-1β Inhibitors, anorectic drugs, sodium-dependent glucose cotransporter-2 inhibitors, engineered zinc-finger protein transcription factors, fibroblast growth factor 21 (FGF-21), adenosine monophosphate kinase (AMPK) activators, and activators of SIRT1 (a member of the sirtuin family of NAD+-dependent protein deacetylases) are other currently available agents.

Bariatric surgery is also capable of producing weight loss and reducing diabetes severity, especially in severe obesity.

Newer therapies aim to improve beta-cell function, among which are the GLP-1 analogs and GLP-1 RAs. By restoring endogenous insulin response in T2DM, they may stabilize or prevent disease progression. Dipeptidyl peptidase 4 (DPP-4) inhibitors are oral agents that increase endogenous GLP-1 levels twofold over the short term.

Moving on from GLP-1 RAs, dual and triple agonist therapy is emerging. These are combinations that target GLP-1 along with GIP or insulin-like growth factors. Tirzapatide (GLP-1 RA with GIPR) is a dual agonist approved in the USA for T2DM therapy in 2022.

Triple agonists target three different receptors, the GLP-1R, the GIPR, and the GCGR, producing complementary but independent impacts on blood glucose and body weight. These are still mostly in the experimental stage. Many such agents are under investigation.

With their multiple effects on metabolism, GLP-1 RAs are also being investigated for obesity management as well as the treatment of neurodegenerative, cardiovascular, digestive, and musculoskeletal disorders. Some like semaglutide (Wegovy) are now approved for weight loss. 

Credit: news-medical.net  

Team Metabolic Health

The cardiovascular benefits of Ozempic and Wegovy have been unveiled in the SUSTAIN 6 trial and the SELECT trial.

On October 21, Novo Nordisk announced positive news on the cardiovascular benefits of its oral glucagon-like peptide-1 receptor (GLP-1R) agonist, Rybelsus, which is currently approved for type 2 diabetes (T2D). According to GlobalData, these results could drive an increase in Rybelsus use, as until now the effects of the drug were not comparable to its injectable alternative.

Novo Nordisk’s oral semaglutide has been on the market under the name Rybelsus since 2019, but the semaglutide injectables, Ozempic and Wegovy, have been the centre of attention since they launched due to their stronger metabolic effects both on T2D and obesity patients. Furthermore, the cardiovascular benefits of Ozempic and Wegovy have been unveiled in the SUSTAIN 6 trial and the SELECT trial. Since then, many prescribers have preferred them to the alternatives for patients with a risk of cardiovascular disease.

The semaglutide injectables, Ozempic and Wegovy, have been the centre of attention since they launched due to their stronger metabolic effects both on T2D and obesity patients. Credit: fcm82/Shutterstock.

The SOUL trial showed a 14% overall risk reduction in major adverse cardiac events (MACE) in T2D patients with cardiovascular disease with or without chronic kidney disease after Rybelsus use, while Ozempic and Wegovy reduced MACE by 26% and 20%, respectively, in the SUSTAIN 6 and the SELECT trials, when compared to patients receiving placebo.

Thus, the SOUL trial may place Rybelsus at an advantage over other oral GLP-1R agonists that are due to reach the market soon and do not have this kind of data yet. It confirms the overall stronger effects of injectable semaglutide over oral semaglutide, but also decreases this gap in efficacy, proving the cardiovascular benefits of Rybelsus. Reducing cardiovascular disease risk is very important in patient populations such as T2D and obesity patients, and according to key opinion leaders interviewed by GlobalData, such benefits could also be a driver for drug reimbursement in the near future.

Credit: clinicaltrialsarena.com

Team Metabolic Health

Best exercises: Start your day with a quick climb for 5–10 minutes to energise your body. This simple change, you can turn an everyday activity into a health-boosting habit. So, lace up your shoes and start climbing your way to better health. Here’s why.

Stair climbing can transform your everyday mundane moments into powerful opportunities for fitness. Whether it’s choosing stairs over an elevator at work or setting aside time at home for a quick climb, this accessible activity offers profound health benefits. From strengthening your heart to boosting mental well-being, climbing stairs is a simple yet impactful way to stay active and healthy.

According to a  study published in PubMed, the updated global and national guidelines on physical activity, emphasis that health benefits can be achieved by accumulating activity throughout the day. Unlike older guidelines that recommended activity in bouts of at least 10 minutes, the new approach recognises the value of even short bursts of movement, such as stair climbing. These brief activities, integrated into daily routines, may be more practical for you than structured exercise sessions.

Health benefits of climbing stairs: This vigorous activity improves blood vessel flexibility, helping lower elevated blood pressure levels. Climb stairs consistently after meals to regulate blood pressure and support circulation (Image: Canva)

Check out the health benefits of climbing stairs everyday:

Burns calories efficiently: Climbing stairs burns 8.6 to 9.6 times more energy than sitting, making it an excellent calorie-torching activity. Just 10 minutes of stair climbing can help manage weight effectively and boost metabolism. Start small by taking the stairs instead of the elevator at work or in malls.

Improves heart health: Regular stair climbing enhances cardiovascular fitness, reducing the risk of coronary heart disease and stroke. It promotes better heart function and circulation. Cardiologists recommend 30 minutes of moderate activity, such as stair climbing, five times a week for heart health.

Lowers blood pressure: This vigorous activity improves blood vessel flexibility, helping lower elevated blood pressure levels. Climb stairs consistently after meals to regulate blood pressure and support circulation.

Strengthens leg muscles: The repetitive upward motion works the quadriceps, hamstrings, calves, and glutes, improving lower body strength. Strong leg muscles support joint health, reducing the risk of injuries and arthritis.

Improves aerobic fitness: Stair climbing increases your aerobic capacity, enabling your heart and lungs to work more efficiently during everyday activities. Gradually increase your pace and duration to improve stamina.

Controls blood glucose levels: Climbing stairs after meals lowers post-prandial glucose levels, aiding in better blood sugar management. Regular activity like this is especially beneficial for those with prediabetes or Type 2 diabetes.

Promotes healthy cholesterol levels: Stair climbing helps improve lipoprotein profiles by increasing HDL (good cholesterol) and reducing triglycerides. Aim for a few short stair-climbing sessions daily to maintain a healthy lipid profile.

Aids in weight management: As a calorie-burning, vigorous activity, stair climbing helps maintain or reduce body weight when paired with a balanced diet. Combining stair climbing with other activities enhances overall metabolic rate, aiding weight loss.

Improves metabolic health: It reduces symptoms of metabolic syndrome, such as high triglycerides, abdominal fat, and fasting glucose, lowering risks of chronic diseases. Include stair climbing during your work breaks to combat sedentary habits.

Boosts mental health: Physical activity like stair climbing releases endorphins, reducing stress, anxiety, and depression while improving overall mood. Engaging in brief bouts of stair climbing can help counteract mid-day stress and fatigue.

Increases bone density: As a weight-bearing exercise, climbing stairs strengthens bones, reducing the risk of osteoporosis and fractures. Women in their 30s and above should practice stair climbing to preserve bone health.

Is convenient and accessible: Stairs are everywhere, at home, offices, malls, and parks. No equipment or gym membership is required, making it easy to stay active. Even short bouts of activity on stairs can meet daily movement goals recommended by health experts.

Supports longevity: Frequent stair climbing is associated with lower all-cause mortality, contributing to a longer, healthier life. Studies show that adding stairs to your routine can improve overall longevity by supporting vital organ functions.

Disclaimer: This article, including health and fitness advice, only provides generic information. Don’t treat it as a substitute for qualified medical opinion. Always consult a specialist for specific health diagnosis.

Credit: moneycontrol.com

50+ unique and unusual boy names with meanings for your baby

The doll has light-blue eyes and strawberry-blonde hair with light-pink tips. Summer wears a signature outfit in rainbow, her favorite color, and is dressed in a rainbow-patterned dress, pink-and-purple ombre glasses, two matching bracelets and platform sandals. Summer also has on theme, adorable accessories like a dog-themed purse and a travel tumbler shaped like an ice cream cone. It’s almost a new year, and that means it’s time for a new American Girl Girl of the Year! The doll for 2025 is Summer McKinny, a dog lover and baker who wants to start her own small business. This 18-inch doll features blue eyes and strawberry blonde hair with pink tips and two face-framing braids.

We’ve compiled the top 100+ most popular boy dog names from American Kennel Club’s purebred registration and mixed-breed enrollment data for 2023 to help you get inspired. Each year, the Social Security Administration releases data on the most popular baby names from the previous year. The report includes the change in popularity, and the database allows you to search by the name and the year.

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Speaking of combining and remixing names, a lot of names on the list of fast-climbers are really alternate spellings of more popular names. Chosen is on there, as it was last year, but the creatively spelled Chozen is higher. There’s also Eiden (alternative to Aiden), Matheo (Mateo) and Dereck (Derrick). These are the cool names of the guys who are good-looking but not pretty, tough but also tender, bad boys but in the best possible way. If this is your prime criteria for a name, forget name style (though many of these are stylish) and focus on names that convey the cool guy image.

Noah has held on to the top spot for a second year running, with the ever popular Oliver moving down to 4th place. There are still plenty of names that are regular fixtures in the top 100 list, such as George, Muhammad, Leo, Harry, Jack, William and Isaac. But there are some more unusual or less traditional options which have shot up the the top 100 chart – or even made their debut – including Leon, Elias, Musa, Axel and Ibrahim. Each year, the ONS analyses the latest baby name data, revealing the most popular – and unpopular – names in England and Wales.

Look for Fox, Bear, Falcon, Lynx and Tiger to show up in the future. When Nameberry made its own list of the top names of 2024 so far, these were the most popular. See the current trendiest names, along with modern names that are up-and-coming. Strictly Necessary Cookie should be enabled at all times so that we can save your preferences for cookie settings.

Check the Social Security Administration for the official rankings, and consult parents in your neighborhood to learn which names are common in your social circle. Are you looking for gender neutral names that won’t reveal your child’s sex? Or would you prefer a name that’s clearly masculine for your little boy? This choice may play into your feelings about gender identity, or be closely tied to style — gender neutral baby names are often very contemporary. The choices listed here are among the Top 1000 most popular boy names on Nameberry but are not among the Top 1000 boy names in the United States.

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Damages and issues Please inspect your order upon reception and contact us immediately if the item is defective, damaged or if you receive the wrong item, so that we can evaluate the issue and make it right. ”One of Scanlan”s great strengths is her gift for writing fully rounded characters, andthis is Scanlan at her very best” Irish IndependentThe City Girls are back! As City Girl, Devlin Delaney’s iconic gym and spa prepares to mark a biganniversary, her best friends,… Fans can further explore Summer’s new world through digital content like AG’s YouTube and YouTube Kids Channel.