Hope everyone is quite well this week. For those dads out there, warm wishes for a very happy Father’s Day!
And I’d also like to note, with deep respect, that tomorrow is Junteenth and a holiday for twenty30 health, as we commemorate the emancipation of enslaved Black Americans on what many view as America’s second Independence Day.
In the spirit of Junteenth, allow me to quote Dr. Benjamin Chavis Jr., CEO & President of The National Newspaper Publishers Association (NNPA), in what is a guiding principle of twenty30 health to bring our multi-modal and comprehensive obesity management to ALL people on a fair and equitable basis:
“We must prioritize combating the obesity pandemic with the same energy we use to combat COVID-19 and racial injustice. Our lives depend on it.”
Please enjoy the long weekend, stay cool and keep healthy, and honored to present this week’s bumper issue!
Kind regards, Raj.
AT A GLANCE
- The Washington Post leads with ‘Insurers clamping down on doctors who prescribe Ozempic for weight loss.’
- The American Medical Association adopts a new policy based upon ‘Use of BMI alone is an imperfect clinical measure.’
- Eileen Isotalo, 66, is profiled in The New York Times, on her lack of food cravings and weight loss of 50 pounds, since she started taking Wegovy.
- John, weighing 430 pounds at age 14, and Edward at 300 pounds in high school, illustrate the ‘…small but growing group of young teens turning to treatments like body-altering surgery and new drugs that rewire metabolism to lose large amounts of weight…’ as per The Washington Post.
- ‘About 101 million Indians are diabetic, a 44 percent rise since 2019…’ is the startling statistic in The Times, referring to a study from the Indian Council of Medical Research.
NEWS
- The Washington Post leads with ‘Insurers clamping down on doctors who prescribe Ozempic for weight loss.’ in reference to letters from insurers to providers on ‘…tightening rules to prevent off-label prescriptions for now.’ The stance from insurer Elevance Health, which operates Anthem’s plans, is ‘…that in most cases it won’t cover Ozempic unless a patient is diagnosed with diabetes and has tried another medication to manage it, but physicians can still prescribe it.’
- ‘The gold rush…’, or significant financial wins, are already being realized on the stock market for medications – from a doubling of the share price of Viking Therapeutics based on a small early-stage trial, to Pfizer’s addition of $10 billion of value to its share price, spurred on by results of a phase 2 safety and efficacy trial in just over 400 adult subjects. Indeed, WeightWatchers stock ‘…jumped 59 percent the day after it announced it completed a deal that will allow it to sell GLP drugs directly to patients.’
- Somewhat unsurprising is the news report from Forbes that ‘…The U.S. market for the new wave of obesity drugs is much larger than Europe’s,’ stemming from Europe’s lower obesity rates, delayed launches, lower product prices, stricter insurance requirements, greater scrutiny on off-label use, and no direct-to-consumer advertising. With this, ‘…Novo Nordisk says it is prioritizing the U.S. market….’ though ‘…in April of this year, Novo Nordisk decided to pause its marketing campaign of the drug.’ Going deeper on the continental divide between the U.S. and Europe, is ‘…at £199 ($250) per month’s supply, Wegovy is considerably cheaper in the U.K. than the roughly $1,300 it is listed at in the U.S.’ In the Netherlands, ‘…there are stringent conditions attached to their reimbursement, including a BMI of 35 or more. A doctor must also examine the root causes of a patient’s obesity.’ And in France ‘…officials openly criticize the deployment of social media to promote Ozempic…’ and ‘…that its use should be reserved solely for treating diabetics.’
- Zachariah Reitano, co-founder and CEO of Ro, writes on ‘The Wegovy Shortage & Full Ownership’ in relation to ‘…the Body Program, a comprehensive obesity program centered around GLP-1s.’ The narrative is focused upon ‘…limited insurance coverage of Wegovy and (its) shortage…’, and continues ‘…that a not insignificant number of patients may be frustrated and direct that frustration to us.’ His solution is based upon increasing calls to pharmacies, issuing credits to patients, expanding the formulary to newer treatments, communicating with current and prospective Wegovy patients, and probably most influentially, pausing key promotional efforts. Fighting for patients, and full ownership, in a resolute public commitment to patients, are the key takeaways.
- A noteworthy story from Allison DeAngelis at STAT News and Ryan Cross at The Boston Globe, regarding Laronde, a company out of the same Flagship Pioneering stable that incubated Moderna, on its assay of an anti-obesity therapeutic based upon the GLP-1 hormone. The article refers to a statement from Laronde, where ‘…the company acknowledged that it had been developing a GLP-1 therapy throughout 2020 and 2021, but has since found that its early experiments were unreliable.’ In continuation, ‘…a clearer picture of our historic GLP-1 efforts emerged in 2022, we engaged our board and investors and took appropriate action.’
- DeAngelis and Cross dig deep on Catherine Cifuentes-Rojas, recruited from a molecular biology assistant position at Massachusetts General Hospital in June 2018 to Laronde, and ‘…tasked with working on the GLP-1 candidate…’ based upon a technology called endless RNA, or eRNA. The narrative focuses upon concerns on Cifuentes-Rojas’ experimental data, an inability to reproduce her laboratory results, and internal skepticism of the work, leading to an eventual parting of ways with Cifuentes-Rojas.
- Jane van Heteren, an ex-Laronde employee who worked on the same team as Cifuentes-Rojas, says ‘…We don’t want to bring the message to the general public that this is what happens in biotech.’
- My two cents: the hype of anti-obesity medications has in the past, and will in the future, lead to more failures than successes, which is part and parcel of the evolutionary process of medical research and subsequent advances in therapy. Hats doffed to Flagship Pioneering and Laronde for taking action here. And importantly, we as a profession must maintain credibility through unrelenting trust and transparency, and avoidance of superlative claims, to advance on this spectacular journey to impact care for people with obesity.
- Ten years after defining obesity as a chronic disease, the American Medical Association adopts a new policy based upon ‘Use of BMI alone is an imperfect clinical measure.’ AMA Immediate Past President Jack Resneck, Jr. MD states ‘…It is important for physicians to understand the benefits and limitations of using BMI in clinical settings to determine the best care for their patients.’ The House of Delegates refers to ‘…issues with the issues with using BMI as a measurement because: Of the historical harm of BMI, Of the use of BMI for racist exclusion, [and] BMI cutoffs are based primarily on data collected from previous generations of non-Hispanic white populations and does not consider a person’s gender or ethnicity.’
- The key takeaway is that ‘…BMI is significantly correlated with the amount of fat mass in the general population but loses predictability when applied on the individual level…’ and further ‘…use of BMI should not be used as a sole criterion to deny appropriate insurance reimbursement.’
- A multitude of factors should be employed including visceral fat, body adiposity index, body composition, relative fat mass, waist circumference, and genetic or metabolic factors. I give huge kudos to the AMA and am keen to engage in how to drive impact to our patients, stemming from this policy statement. We need a whole-person approach to caring for individuals with obesity and related metabolic disease – the BMI-centric approach is akin to managing a patient with breast cancer just by the size of the tumor, and nothing else. BMI is a part of the toolbox for sure, and easy to measure; but it should not be the sole criterion.
OPINION
- Owen Tripp, CEO of Included Health, ‘…an integrated care delivery and navigation company working with employers and health plans…’ references in STAT News the polarizing views of ‘…obesity as a moral failing, a lack of willpower…’ and more recently ‘…as a medical issue that can be cured by a pill.’ I applaud this simple yet effective statement of truth. He writes on his company’s role to assist employers ‘…make the best decisions on behalf of their employees about guiding and delivering healthcare…’ and to do so ‘…as part of a comprehensive care plan to improve health overall.’ An entire paragraph is devoted to the unknowns on return of investment of GLP-1 medications, with inclusion of numbers that not everyone will lose 15-20% of their total body weight, and of the need for ‘…patients stay on the medication for life.’ The obvious ‘…tension between optimism and skepticism…’ is clearly at odds ‘…when workers demand the drug and bosses balk at the cost…’ with a prediction that ‘…all these new pop-up programs offering GLP-1s will pop down again.’ The most captivating piece here for me is on the bigger issue to ‘…destigmatize [weight] as much as mental health.’
- Eileen Isotalo, 66, is profiled in The New York Times, on her lack of food cravings and weight loss of 50 pounds, since she started taking Wegovy. Whilst her ‘…obesity-related medical problems have vanished along with much of the stigma that caused her to retreat from family and friends…’ there remain ‘…struggles with the fear others will judge her for receiving injections to treat her obesity rather than finding the willpower to lose weight and keep it off.’ Dr. Susan Yanovski, co-director of the office of obesity research at the National Institute of Diabetes and Digestive and Kidney Diseases puts it well in that ‘…People really believe that people with obesity just need to summon their willpower and they think that taking a medicine is the easy way out.’ This takes me back to many of my patients over the past twenty years who have been fearsome of taking the ‘easy way out’ with bariatric surgery – would we think that of an individual who has surgery to excise their invasive skin cancer, undergo hip replacement for their painful and limiting osteoarthritic joint, or have their troublesome tonsils removed – really? Or for a patient who takes beta blockers for their blood pressure, eye drops for their glaucoma, or undergoes in vitro fertilization to start a family? Imagine if we said to the childless couple, just keep trying harder, in their quest to get pregnant. Gina Kolata, the author, repeats my narrative on the unintended social consequence to weight loss in the form of ‘…Obesity medicine specialists say they are not surprised – they see the same thing after people lose weight with bariatric surgery.’ We eat with our family, our friends, our co-workers – when we eat different types of food, less often and in moderation, the social construct of tailgate parties, all you can eat buffets, and Sunday cookouts are no longer plausible. Indeed, ‘…relationships shift because obesity is such a defining condition…’ and we need to support and guide our patients, and their communities, through these important transitions, over the long-term.
- John, weighing 430 pounds at age 14, and Edward at 300 pounds in high school, illustrate the ‘…small but growing group of young teens turning to treatments like body-altering surgery and new drugs that rewire metabolism to lose large amounts of weight…’ as per The Washington Post. Importantly, the article notes ‘…Eighty percent of adolescents with excess weight carry it into adulthood, with potentially dire consequences for their health and longevity.’ The views from society, clinicians, parents, and the adolescents themselves on treatment with medication and surgery, range from ‘…get on it early…’ to ‘…dangerous and disheartening…’ and from Dr. David Ludwig, an endocrinologist and researcher at Boston Children’s Hospital, to ‘…diet and exercise must remain at the forefront.’ In contrast, Dr. Janey Pratt, a surgeon at Stanford University, says ‘…diet and exercise alone aren’t enough…’ and more directly analogizes her patients’ disease status ‘…with a train that’s headed over a cliff.’ John, who was operated on by Dr. Pratt, is now 15 years old, and ‘…has learned to cook healthy meals, like a recent dinner of sauteed shrimp and chard. He works out at a local gym, puts 18,000 steps on his pedometer every day and hopes to study hard to land his dream job as an automotive engineer.’ Kudos to John for radically improving his lifestyle, akin to his desire to ‘…want to live a happy, healthy life…’ and ‘…just without the weight.’
- Matt Reynolds at WIRED magazine, wants the reader to ‘…get a sense of where these [GLP-1] drugs came from – and where they might go next…’ in speaking with Jens Juul Holst at the University of Copenhagen in Denmark, and Joel Habener at the Mass General Research Institute, who ‘…were awarded the Warren Alpert Foundation Prize [in 2020, and considered a primer for the Nobel Prize] for their work discovering and developing treatments based on the GLP-1 hormone…’ together with Daniel Drucker, from the University of Toronto. Whilst the historical narrative is interesting, the approach on mechanism of action, as per Dr. Holst to ‘… lose your appetite and also the pleasure of eating, and so I think there’s a price to be paid when you do that. If you like food, then that pleasure is gone…’ and continues ‘…that once you’ve been on this for a year or two, life is so miserably boring that you can’t stand it any longer and you have to go back to your old life.’ Dr. Holst is more forceful ‘…It’s not the question of money. It’s simply because something happens that makes you uninterested in going on…’ and closes with ‘…I don’t see that a huge part of the population will be put on Wegovy and will stay on Wegovy for the rest of their lives — I simply don’t see that picture, because this hasn’t happened with other GLP-1 drugs.’ Wow!
- Touted as a function of the Ozempic weight-loss craze, Nidhi Subbaraman writes in The Wall Street Journal on ‘…new interest in a dietary supplement with roots in ancient traditional medicine as a cheap way to shed pounds.’ Berberine, a natural supplement has been ‘…dubbed nature’s Ozempic…’ with ‘…millions of views on the social network TikTok…’ and available online in pill or powder form, at around $6 to $37 for a two-month supply. Dr. Elizabeth Bradley, medical director at the Cleveland Clinic’s Center for Functional Medicine, is quoted ‘I’m pleasantly surprised at the impact…’ in her patients ‘…for glucose, cholesterol and weight concerns.’ As with any supplement, berberine is not FDA approved, the research data is weak, and the quality of berberine supplements varies widely.
DATA
- An Editorial article in The New England Journal of Medicine on the topic of childhood obesity, refers to leptin, a peptide hormone made predominantly by adipose [or fatty] tissue, whose congenital absence from a genetic disorder, causes severe early-onset obesity.
- ‘About 101 million Indians are diabetic, a 44 per cent rise since 2019…’ is the startling statistic in The Times, referring to a study from the Indian Council of Medical Research, and further that ‘…136 million Indians were pre-diabetic…’ and ‘…254 million Indians are also classified as obese.’ Johnrose Jayalal, the former president of the Indian Medical Association was quoted ‘…We have to educate children on lifestyle and identify diabetes early on at our primary healthcare centres. Doctors have to focus on prevention otherwise it will become unmanageable’, which is certainly true, though when the numbers of the population with obesity, diabetes and pre-diabetes are so large – primary prevention is deeply challenged. We need to focus our attention and resources on secondary prevention to avoid people with obesity developing diabetes and hypertension, and tertiary prevention to prevent those with diabetes to develop kidney and eye disease, and those with hypertension to develop heart attacks and stroke.
- Researchers from Amsterdam University Medical Centers, Yale University and Albert Einstein College of Medicine, publish research in Nature Metabolism on brain responses in healthy body weight and obese human subjects, after nutrient intake. Brain activity, measured by functional MRI, in healthy weight subjects led to signals that regulate eating behavior, though in obese subjects, there were ‘…severely impaired brain responses to post-ingestive nutrients.’ Furthermore, when the obese subjects loss 10 per cent of the total body weight through diet, the ‘…impaired neuronal responses are not restored…’ and ‘…may contribute to overeating and obesity, and ongoing resistance to post-ingestive nutrient signals.’ This may further ‘…explain the high rate of weight regain after successful weight loss.’ Whilst the data is preliminary at best, the research study adds weight to the narrative that obesity is not simply a lack of willpower; biological mechanisms are at play… and are very hard to modify, even after significant weight loss.
- Researchers across four US pediatric primary care sites, with 452 children aged 6 to 12 years with overweight or obesity, their parents, and 106 siblings, sought to deliver ‘…Family-based treatment used a variety of behavioral techniques to develop healthy eating, physical activity, and parenting behaviors within families…’ over ‘…26 sessions over a 24-month period with a coach trained in behavior change methods.’ As per their published article in the Journal of the American Medical Association, at 24 months ‘…children receiving family-based treatment had better weight outcomes than those receiving usual care…’ based upon a reduction in BMI. Even more interesting is that ‘…Siblings who were not directly treated also had improved weight outcomes, suggesting that this treatment may offer a novel approach for families with multiple children.’ Let me share with you an example of one of my patients who had undergone bariatric surgery, and after nine months was doing great having lost over eighty pounds and reduced her chronic disease burden; not only was she ecstatic, but she recounted to me that her husband had lost twenty pounds, and each of her teenage kids had also lost ten to fifteen pounds – the social network impacts are impressive and need to be studied and implemented more actively.
Kind regards, Raj
