A Billion People Obese Worldwide; An Obesity Vaccine? – from Novo Nordisk and Vivani; Survodutide for Liver Disease; Bariatric Surgery Cures Diabetes


    • STAT reports on Marcus Schindler, Novo’s chief scientific officer, who wants to ‘…make long-lasting GLP-1 molecules…’ with ‘…vaccine-like properties.’
    • NPM-115 and NPM-139 are miniature, subdermal GLP-1 implants from NASDAQ-listed company Vivani Medical, Inc. that provide once- or twice-yearly administration.
    • STAT reports from a study in The Lancet that ‘…more than 1 billion people – or one in eight people worldwide – are now estimated to have obesity.’
    • Boehringer Ingelheim reports on survodutide, a glucagon/GLP-1 treatment for obesity, with 83% improvement in patients with liver disease due to MASH.
    • Viking Therapeutics announced an up to 15% total weight loss at just 13 weeks, for patients on once-weekly GLP-1/GIP drug VK2735.
    • JAMA, published that of 18% of patients with diabetes undergoing bariatric surgery were free of their diabetes, at seven years.


    • STAT in Boston reports on Marcus Schindler, Novo’s chief scientific officer, who wants to ‘…make long-lasting GLP-1 molecules…’ with ‘…vaccine-like properties, where imagine you had, once a year, an injection with an equivalent of a GLP-1 that really helps you to maintain weight loss and have cardiovascular benefits.’
      • An exciting and game-changing proposition is that ‘…one day you can imagine that your body weight set point truly resets and you can enjoy life at a healthy weight without pharmacotherapy.’
      • Novo Nordisk is on a mission to eliminate obesity altogether through RNA interference, or even gene therapies.
    • NPM-115 and NPM-139 are miniature, subdermal GLP-1 implants from NASDAQ-listed company Vivani Medical, Inc. for chronic weight management.
      • The implant can provide once- or twice-yearly administration, to improve medication adherence and medication tolerability, as noted by Adam Mendelsohn, Vivani President and CEO.
      • In a study of ‘…high-fat diet-induced obese mice, NPM-115 generated weight loss of approximately 20% compared to a sham implant control after a 28-day treatment duration…’ which is certainly impressive.
    • STAT reports from a study in The Lancet that ‘…more than 1 billion people – or one in eight people worldwide – are now estimated to have obesity.
      • Obesity rates from 1990 to 2022 quadrupled among children and teens, while rates among adults more than doubled.
      • That comprises ‘…159 million children and teens with obesity, and 879 million adults, with ‘…biggest increases in youth obesity rates occurred in Polynesia and Micronesia and the Caribbean.’
      • Indeed, obesity, and diseases like diabetes, that have traditionally been associated with high-income countries, are increasingly affecting low- and middle-income countries.
      • Francesco Branca, director of nutrition and food safety at the World Health Organization noted GLP-1 medications ‘…are definitely an important tool, but they should not be seen as a solution to the problem…’ with a greater focus on ‘…transformation of food systems and the environment, such that obesity can be prevented.’
      • I disagree – prevention is an enigma – we need to be fully immersed in treatment of obesity as a chronic disease.


    • Elaine Chen at STAT notes 23 of over 100 obesity treatments in development or on the market are being investigated for metabolic dysfunction-associated steatohepatitis, the fatty liver disease known as MASH.
      • Known previously as NASH, the disease affects about 5% of American adults, or 12 to million people – worthy of a multibillion dollar product.
      • Dr. Meena Bansal, chief of the division of liver diseases at Mount Sinai in New York is working on several trials of obesity drugs in MASH, said ‘…it really opens up our armamentarium to treat MASH.’
      • Novo Nordisk has conducted clinical trials on Wegovy for MASH, as is Eli Lilly on its Zepbound phase two trial.
      • In addition, Eli Lilly is working on retatrudite, also known as triple-G as it works on GLP-1, GIP and glucagon hormones.
      • Bansal added ‘…we are in a very exciting time where we are going to have a larger toolbox…’ to treat the liver disease.
      • In addition, MASH is a considerable cost driver for payors, and if treatments lead to resolution, there will be a significant reduction in total costs of care – which in my opinion should drive greater and earlier adoption for this patient group.
    • Darius Mozaffarian at the Friedman School of Nutrition Science and Policy, within Tufts University, Boston, writes in JAMA on GLP-1 Agonists for Obesity – A New Recipe for Success?
      • He notes ‘…clinical and public confusion exists around real-world costs, tolerability, and access…’ with 93 million Americans meeting weight-loss eligibility criteria.
      • The dilemma is clear: ‘…an initially effective but costly, difficult-to-sustain program of chronic GLP-1 agonist use, versus a less costly but less effective strategy of older drugs plus behavioral coaching.’
      • The author proposes a ‘…new paradigm of initial, staged GLP-1 agonist treatment supported by long-term lifestyle programming that addresses structural barriers…’ comprising initial GLP-1 agonist therapy, with booster periods over time, lifestyle counselling including food is medicine [FIM], leveraging telehealth, apps, peer support, artificial intelligence, and gamification.
      • He goes on to ask whether GLP-1 agonist and FIM programs make ‘…effective, cost-effective, and equitable obesity treatment be within reach?’



    • Boehringer Ingelheim reports on survodutide, a glucagon/GLP-1 treatment for obesity, in patients with liver disease due to MASH.
      • Up to 83% of adults treated with survodutide achieved a statistically significant improvement of metabolic dysfunction-associated steatohepatitis (MASH) versus placebo [18.2%] in a Phase II trial, at 48 weeks.
      • The press release notes the ‘…glucagon agonist component in survodutide has the potential to increase energy expenditure…’ while the ‘…GLP-1 agonist component decreases appetite while increasing fullness and satiety.’
      • Dr. Arun Sanyal at Virginia Commonwealth University School of Medicine, and Principal Investigator of the trial was ‘…thrilled to see these statistically significant results from the Phase II trial of survodutide in MASH and fibrosis.’
      • Carinne Brouillon at Boehringer Ingelheim noted the ‘…MASH results show survodutide has potential to become a best-in-class treatment, and we believe its true differentiator is the action of the glucagon receptor agonism which works directly on the liver.’
      • Shares of partner company Zealand Pharma rocketed by 35% this week, in what is becoming more than just a two-horse race between Eli Lilly and Novo Nordisk.
    • Viking Therapeutics announced an up to 15% total weight loss at just 13 weeks, for patients on once-weekly GLP-1/GIP drug VK2735, in a phase 2 clinical trial.
      • In addition, 88% of participants reporting over 10% total weight reduction.
      • The San Diego based company enjoyed a doubling of their share price this week.
      • Viking CEO Brian Lian said there was no plateau over the 13 weeks, ‘…suggesting further weight loss might be achieved from extended dosing periods.’
      • Tirzetpaide, or Zepbound, has the same mode of action on both GLP-1 and GIP hormones; it will be critical to note results farther out, to one year and beyond, for those on the drug.
    • The Lancet Diabetes & Endocrinology published on the UK-based DiRECT trial on patients with diabetes and obesity resulted in weight loss, with remission of type 2 diabetes in 36% of the group, at two years.
      • At extension of the trial to five years, to include additional dietary support, almost two-thirds of subjects were off glucose lowering medication, and one-third were in remission of their diabetes.
      • These data suggest weight management may help to delay or avoid clinical complications of diabetes, though not all people will succeed with purely dietary intervention.
      • The new and highly effective GLP-1 agonists offer additional support for weight management, with opportunities to reduce the burden of type 2 diabetes.
    • JAMA, a high-profile medical journal, published from Anita Courcoulas and colleagues on long-term outcomes of medical management versus bariatric surgery in type 2 diabetes.
      • In just over 260 patients, 18% of those undergoing bariatric surgery were free of their diabetes, or in remission, at seven years, and had less medication use too.
      • Drs. Thomas Wadden and Robert Kushner write an Editorial to support the expanded use and coverage of bariatric surgery for the 14% of adults in the US affected by diabetes, comprising over $300 billion of annual direct medical costs.
    • Virta Health publishes a review on the effect of GLP-1 deprescription on glycemia and body weight following carbohydrate restricted nutrition therapy [CRNT], or a ketogenic diet.
      • Almost 70% of patients with type 2 diabetes who stopped taking their GLP-1 medication were able to maintain at least 5% total weight loss at one year.
      • Just shy of one-third of subjects were previously on semaglutide, with almost half on dulaglutide, or Trulicity.
      • The data are preliminary and not gospel for sure, though the accompanying press release suggest patients can ‘…decide they don’t want to be on GLP-1s long term and use Virta as a safe and sustainable off-ramp to the drugs while maintaining a healthy weight.’



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