Let’s do right and SELECT the best for our patients suffering from obesity.

Hello everyone,

I hope you are all enjoying this weekend in good health. Here at twenty30 health, our hearts go out to everyone impacted by the wildfires in Maui, and we share in the sense of tragedy and horror at these terrible events.

Our focus of this newsletter is the onward media and corporate hype around GLP-1 medications — this week significantly enhanced by a one-page press release from Novo Nordisk on the top line results of the SELECT study. Over 17,000 subjects treated on semaglutide [Wegovy] were followed over a five-year period; with the result being the achievement of a 20% reduction in major adverse cardiovascular events, or MACE. Novo Nordisk now has a market capitalization of $300B, approaching the total value of the economy of its home country Denmark.

This is not to say that the SELECT study isn’t groundbreaking, especially in terms of advancing society’s understanding of obesity as a chronic disease, and how interventions such as medication can be truly life saving. Having said this, we do need to see the detailed results of the study, scheduled to be presented in Q4 of this year. And of course, we need to translate these results into real-world evidence outside of a clinical study.

Most importantly, we should view these GLP-1 results in the context of delivering multimodal, whole person care, over a multi-year period to all those that suffer from obesity and related metabolic disease, taking into account for example that a 50% reduction in MACE and up to a 60% reduction in heart attacks is available to many patients through bariatric or metabolic surgery. How we support and assist our patients to deliver such groundbreaking care, through the engagement of our fellow clinical providers, has the potential to save lives and reduce suffering for over 100 million Americans, and billions across the globe.

I look forward to the coming few weeks, when the fever pitch is going to level out, and we can come back down to the ground to meet all our patients where they are, and help them to get to where they want to be — to live their fullest lives possible.

Kind regards, Raj.


  • Novo Nordisk was the biggest news story of the week, with announcement on the SELECT study of over 17,000 adults had achieved ‘…its primary objective by demonstrating a statistically significant and superior reduction in MACE [major adverse cardiovascular events] of 20% for people treated with semaglutide [Wegovy] 2.4 mg compared to placebo.’  
  • Novo Nordisk announced this week a $1 billion purchase of Inversago Pharma, a Montreal-based biotech working on cannabis-receptor based ‘…therapies for the potential treatment of obesity, diabetes and complications associated with metabolic disorders.’
  • Katie Palmer at STAT News focused upon ‘…wild west of online prescribers…’ for patients seeking novel weight loss medications.
  • Tele-CBT demonstrated significant reductions in eating psychopathology, depressive symptoms, and anxiety symptoms in patients one year after bariatric surgery, with a shift in focus of obesity care to health and quality of life outcomes rather than weight loss alone.


  • Novo Nordisk was the biggest news story of the week, with announcement on the SELECT study of over 17,000 adults ‘…aged 45 years and older with overweight or obesity and established cardiovascular disease (CVD) with no prior history of diabetes…’ had achieved ‘…its primary objective by demonstrating a statistically significant and superior reduction in MACE [major adverse cardiovascular events] of 20% for people treated with semaglutide [or Wegovy] 2.4 mg compared to placebo.’ MACE comprises cardiovascular death, non-fatal myocardial infarction [or heart attack], and non-fatal stroke.
    • Of note, the press release notes the intervention group had a ‘…a safe and well-tolerated profile in line with previous semaglutide 2.4 mg trials…’ which has been the death knell to past anti-obesity medications, in terms of cardiovascular adverse events.
    • Martin Holst Lange, EVP for Development at Novo Nordisk stated this ‘…landmark trial [and] has demonstrated that semaglutide 2.4 mg has the potential to change how obesity is regarded and treated.’
    • We have finally come to know and accept obesity as a chronic disease, fueling ill health through impacts on the cardiovascular, pulmonary, hepatic [or liver], musculoskeletal organ systems, and behavioral health too – with this, the news that semaglutide can reduce disease burden and death in those with pre-existing cardiac disease and obesity is impressive. Importantly for the field of obesity medicine, this is not a new finding – we have known for over a decade that bariatric surgical interventions such as gastric bypass and gastric sleeve, through their mode of action to elicit a permanent GLP-1 agonist response in the patient, may lead to an over 50% reduction in MACE, up to 60% reduction in myocardial infarction. In addition, the SELECT trial recruited patients over a five year period, and it is going to be of additional interest whether the reductions in disease burden and death rate occurred earlier or later during the study period, and second, how the outcomes were related to weight loss – was there a so-called dose-response effect, in which lower risk of MACE was accompanied by higher degree of total weight loss, or perhaps additional factors beyond weight loss were at work.
  • The SELECT study was covered by a number of news outlets; with the general take of this being a landmark trial
    • Elaine Chen and Andrew Joseph report in STAT News on ‘…results that could streamline insurance coverage and spur even greater demand for the highly popular therapy…’ with a basis upon long-term cardiovascular benefits of a weight loss medication. Emily Field, an equity analyst at Barclays in London, wrote in a note ‘If they play baseball in Denmark…Wegovy just hit a home run…’ further exemplified by the 14% uptick in stock price earlier this week. Despite the enthusiasm, payors continue to balk at the monthly price of the drug as they remain unclear on the return on investment for their beneficiaries.
    • Anthony Comuzzie, CEO of The Obesity Society was quoted in a story from Simar Bajaj and colleagues at STAT News that this will ‘…help address what he called the misconception – both within the medical field and in the broader population – that treating obesity is a cosmetic choice, rather than a medical necessity.’ In addition, Dr. Joseph C. Wu, President of the American Heart Association and Director of the Stanford Cardiovascular Institute, and incidentally someone that I worked with over a decade ago at UPenn, said ‘It is quite surprising that semaglutide […] can have such a dramatic result over the 5-year trial period…’ with concerns for what happens when the patient comes off the medication.
    • Similarly, Benjamin Mueller at The New York Times reviews Craig Garthwaite, a health economist at Northwestern University’s Kellogg School of Management, concerns on denial of coverage by payers, with it being ‘…difficult to make the argument that this isn’t part of an essential health benefit when there are cardiovascular benefits.’
    • In another baseball analogy, Evan Seigerman, at BMO Capital Markets, called it a ‘home run scenario…’ as per reporting from David Wainer at The Wall Street Journal.
    • Wainer’s colleague, Peter Loftus quotes Dr. Ania Jastreboff at Yale University School of Medicine, who enrolled patients in the SELECT study, and consults for Novo Nordisk, ‘…Here you’re demonstrating clear improvement in health outcomes…’ with which Novo ‘…plans to present full results at a scientific conference later in 2023.’ Indeed, the ‘…positive result should be meaningful for payers to drive improved coverage…’ including Medicare, according to Jefferies analyst Peter Welford.
    • Lisa Jarvis at The Washington Post suggests the new data from the SELECT study ‘…puts insurers in the increasingly uncomfortable position of justifying their refusal to pay for the new class of injectable weight-loss treatments known as GLP1 drugs.’
    • Berkely Lovelace at NBC Nes notes ‘…that a weight-loss drug has medical benefits beyond weight reduction.’ Shauna Levy, bariatric surgeon at Tulane Bariatric Center in New Orleans says ‘Twenty percent is huge…’ in reference to the reduction in MACE, or major adverse cardiovascular events in the SELECT study, and continues this is ‘…the tip of the iceberg to show the health benefits of these medications.’
  • In KFF Health News, Rachana Pradhan reports Novo Nordisk engaged ‘…Black health experts who support Medicare coverage of drugs used to treat obesity…’ including Dr. Fatima Cody Stanford from Harvard University. There is intent to introduce ‘…coverage for anti-obesity medications in Medicare Part D…’ through the Treat and Reduce Obesity Act, or TROA. Novo Nordisk had ’…enlisted Black music and entertainment stars Queen Latifah and Yvette Nicole Brown…’ back in 2021, both of whom have ‘…openly talked about obesity.’ Indeed, ‘…based on BMI, 50% of non-Hispanic Black adults in the U.S. are classified as obese, the highest rate for any race or ethnicity.’
  • Andrew Joseph at STAT News refers to Novo Nordisk, during its latest earnings report on Thursday where CEO Lars Fruergaard Jørgensen referred to the ‘overwhelming demand for Wegovy…’ in line with celebrations on the top-line findings on the SELECT study. Indeed, on the Eli Lilly earnings call this week, Michael Mason, the president of the company’s diabetes unit, said the SELECT results ‘…should really support access for any payers who are on the fence on whether they should add anti-obesity medications or not.’
  • In a triple whammy, building on the SELECT study and recent earnings report, Novo Nordisk announced this week a $1 billion purchase of Inversago Pharma, a Montreal-based biotech ‘…of CB1 receptor-based therapies for the potential treatment of obesity, diabetes and complications associated with metabolic disorders.’ The lead small molecule candidate is ‘…INV-202, an oral CB1 inverse agonist… designed to preferentially block the receptor protein CB1 – which plays an important role in metabolism and appetite regulation.’ Francois Ravenelle, CEO at Inversago Pharma commented that ‘…this combination will help unlock the full medical potential of our CB1 blockers… for people living with metabolic syndrome, obesity and related complications.’ The company employs 22 people, recently presented a phase 1b study on 37 subjects with 7lbs weight loss over a 28-day period, and no serious adverse events, and is in process with a phase 2 study.
  • Prarthana Prakash at FORTUNE reports Novo Nordisk is ‘…now more valuable than the entire economy of its native Denmark.’ Its $300 billion market cap on the U.S. stock exchange is hot on the heels of ‘…Bernard Arnault’s luxury brand group LVMH as Europe’s largest company by market cap…’ which is in due part due to the stock price bump achieved this week following announcement of top line results from the SELECT study.


  • Aside from news of the SELECT study, Katie Palmer at STAT News focused upon ‘…wild west of online prescribers…’ for patients seeking novel weight loss medications. Briana Lawson, 47 with diabetes, had tried diets, Weight Watchers, Nutrisystem, and considered surgery, until she was ready to give GLP-1 medication a try… her online search pointed to Found, Calibrate, and others. Scott Kahan, director of a weight management clinic in Washington, D.C. said the ‘…world of obesity and weight loss treatments and products have forever been a wild west…’ and are ‘…are the product of a broken system.’ Palmer states ‘…The most dangerous and predatory online weight loss services, experts agree, are those that begin and end with a prescription…’ with ‘…same-day appointments, easy prescriptions, and the promise of losing weight easily without diet or exercise.’ The due diligence before prescribing a GLP-1 medication varies from ‘…asking patients a lengthy list of questions, conducting video intake visits, and ordering blood work to check for undiagnosed metabolic conditions…’ through to ‘…nothing more than a glorified Google form.’ Indeed, virtual-first care has ‘…the potential to drive improved access, too – but only if it prioritizes patients over profits.’


  • Dr. Sockalingham and colleagues at the University Health Network in Toronto sought to explore the effectiveness of a ‘…telephone-based cognitive behavioral therapy (tele-CBT) intervention delivered at 1 year after bariatric surgery…’ on 306 patients, ‘…in improving weight loss, disordered eating, and psychological distress.’ The intervention group received 6 weekly 1-hour sessions and a seventh booster session 1 month later, conducted by 5 clinical psychology doctoral students with experience in the assessment and treatment of patients who underwent bariatric surgery. The control group received standard postoperative bariatric care. Tele-CBT improved disordered eating [measured on the self-reported Binge Eating Scale and Emotional Eating Scale] and psychological distress [with the Patient Health Questionnaire 9-item scale (PHQ-9) and Generalized Anxiety Disorder 7-item scale (GAD-7)], though there was no change in short-term weight outcomes. The JAMA Network Open publication concludes that the intervention demonstrated significant reductions in eating psychopathology, depressive symptoms, and anxiety symptoms after bariatric surgery, with a shift in focus of obesity care to health and quality of life outcomes rather than weight loss alone.
  • Trilliant Health, an industry-leading data analytics and market research company, reported research on behalf of STAT News that ‘…found about 3.6 million people with a prescription claim for a GLP-1 – semaglutide, tirzepatide, or injectable liraglutide without insulin – in 2022.’ Only 53% of people had a matching medical visit claim within three days, suggesting ‘…the other 47% of patients who used their insurance to pay for a GLP-1 – around 1.7 million Americans – may have gotten their prescription without a typical doctor visit billed to insurance.’ Writer Katie Palmer infers ‘…Direct-to-consumer telehealth companies top the list of possible non-traditional sources for these prescriptions…’ with the likes of Calibrate and Ro who ‘…claim to have reached tens and hundreds of thousands of patients with their weight loss medication programs.’ Allison Oakes, director of research at Trilliant Health agrees ‘…that most of those are likely coming from a direct-to-consumer arrangement outside of insurance…’ further denoted by Dr. Nisha Patel with the term ‘prescription as a service’. Dr. Caroline Apovian, at the Center for Weight Management and Wellness at Brigham and Women’s Hospital in Boston has a great point, in that ‘…telemedicine companies should partner with academic and community practices.’

Kind regards, Raj


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