WHO, GLP-1s and more: perspectives across metabolic and obesity care – 4/2


  • New data on Rybelsus oral GLP-1 medication from Novo Nordisk, in addition to newbie GLP-1/GIP medication [akin to Mounjaro from Eli Lilly] from Viking Therapeutics, code-named VK2735. The anti-obesity medication market is hotting up, with aligned stock price increases across the board.
  • Are anti-obesity medications the next frontier in saving millions of lives across the globe, akin to medications for sufferers of AIDS in the 1980s – the World Health Organization may be moving in such a direction, according to Reuters News.
  • Two survey studies [here and here] state that many more people are concerned about their weight and are considering medication and surgical therapies, with the narrative being to talk to your doctor and get help.


  • This week marks the 75th anniversary of the World Health Organization, with World Health Day on April 7 2023. The key message is Health for All, that ‘…envisions that all people have good health for a fulfilling life in a peaceful, prosperous, and sustainable world.’


  • Allison Gatlin in Investor’s Business Daily reported ‘Novo Nordisk stock popped to a record high Friday after higher doses of its popular drug, semaglutide, led to greater weight loss in diabetes patients.’ Whilst market dynamics are of course of interest to corporate types and investors, I am pleased to see an appreciation for medication adherence issues that I have mentioned in the past; Umer Raffat, an analyst at Evercore ISI, states that ‘Oral drugs must be taken daily vs. a weekly injection for Ozempic. Oral medications also carry a tricky dosing regimen that involves timing out when to eat food’ and as such, we need to see the medium- to long-term outcomes in the real world, outside of tightly controlled clinical trials.
  • Reuters reports from London on the consideration of drugs to combat obesity being added to the World Health Organization’s ‘essential medicines list’ to ‘…guide government purchasing decisions in low- and middle-income countries.’ There is concern on long-term data in terms of safety and effectiveness which will need to be tempered by the WHO committee. Though more positively, and in alignment with my narrative two weeks ago on this SubStack channel on how we may think differently about discrimination and bias against people with obesity, referencing the predominant approach to gay men with AIDS in the 1980s, the article states ‘…Experts say that adding HIV drugs to the list in 2002 helped to make them much more widely available to AIDS patients in poorer countries.’
  • The Canadian Province of British Columbia ‘…is taking actions to ensure that diabetes patients in B.C. do not experience a shortage of the diabetes drug semaglutide (Ozempic) in an environment where surging demand in some jurisdictions is creating shortages.’ The release from BC Gov News, ‘…indicates that an unusually high percentage of the dispenses of Ozempic are being purchased by U.S. patients from pharmacies located in British Columbia.’ comprising 15,798 dispenses, or 15% of all dispenses of Ozempic in January and February 2023, compared to 0.4% for the average of other drugs sold to Americans. Of deeper interest is that ‘…two B.C. pharmacies were responsible for 13,197 of the 15,798 dispenses to U.S. residents’ based upon the earlier note that ‘…U.S. customers are turning to Canadian online pharmacies to buy drugs at prices lower than can be obtained domestically…’ it is going to be valuable to see how this plays out, with clear focus on the interactions between Novo Nordisk and the B.C. government.


  • The story of Debra Tyler’s daughter, a pre-diabetic teen treated with Ozempic, is featured in The Washington Post, focused upon ‘…a drugmaker that had set mind-blowing monthly costs for medications that might need to be taken for life, and a health insurer that refused to cover them.’ The article quotes a 2022 report that ‘…an estimated 30 to 40 percent of commercial health insurance plans and 19 Medicaid programs cover anti-obesity drugs at some level…’ which I think is an overestimate for the newer GLP-1 medications. The narrative continues with a series of blame-the-other quotes, from David Allen at America’s Health Insurance Plans upon pharma, ‘…we know the problem is the price – a therapy is useless if no one can afford it…’ to Novo Nordisk incriminating payors, ‘…to ensure these medicines are covered by government and commercial insurance plans…’ to United Healthcare ‘…referring to Wegovy as an “appetite suppressant” that is part of a list of excluded categories of medications…’ And where did this lead? Tyler, her husband, and her daughter ‘…began to consider more radical options, including seeking loans or dipping into savings…’ and finally settling for a local pharmacy where she took ‘…a stack of cash out of her purse – $831 in mostly small bills – and pushed it across the counter.’
  • Daniela Hernandez, health and science reporter at Wall Street Journal, released a jam packed four-minute informational video on mechanisms of action of GLP-1 medications, the impact on weight loss to over 15% of body weight, the additional effect of tirzetapide on GIP pathways, and the social media craze of such drugs. There is concern on telehealth sites that connect individuals to doctors who can prescribe such drugs, even for those who do not meet criteria for medication use. The risk of weight recurrence after stopping the drugs, the unknown long-term side effects, and the current price of up to $1,300 per month, are also mentioned.
  • Jillian Michaels, celebrity weight loss and exercise guru, writes in Newsweek to dispel the narrative on the genetic basis of obesity, slamming down Dr. Fatima Cody Stanford personally, with ‘…These narratives are untrue. There is zero data to back up either claim and a robust amount of data contradicting them. Dr. Cody’s claim is also patently false.’ With a focus on the increased rate of overweight and obesity over the past 70 years in the US, from 5% to over 60%, Ms. Michaels claims ‘…That’s one hell of a quantum leap for genetics.’ which clearly illustrates to me the well-known phrase a little knowledge is a dangerous thing. For myself as a clinician scientist, having worked with world-renown researchers and clinicians across the globe in metabolic and obesity care for over two decades, I urge Ms. Michaels to refrain from slapdash comments – there is ample published evidence on the interplay of genetic, epigenetic, environmental, and social factors that predispose individuals toward overweight and obese states, underpinned by neurologic, hormonal, and metabolic pathways.  I further cringe at the list of side effects listed ‘…straight from Ozempic’s website’ and do wish that the author would frame the consequences of overweight and obesity on life expectancy, quality of life, co-morbid diseases including type 2 diabetes, hypertension, sleep apnea, and many common forms of cancer. So her comment ‘…That’s a hefty price to pay, is it worth it?’ may be contested by many of my past patients who have undergone life-changing [and some would say life-saving] treatment in a bariatric surgery program, to enable them to come off their insulin, dispose of their CPAP machine, to start working again, and build happier and more fulfilling lives. The article finishes with the ‘…words of Nancy Reagan, “Just say no”’ … which are just so painful to read.


  • Dr. Kothari, a bariatric surgeon in South Carolina and immediate Past President of the American Society of Metabolic and Bariatric Surgeons, together with colleagues from New York and Chicago, reports on a web and phone survey of over 1,700 Americans to determine whether their ‘…views on obesity have changed after more than two years of living through COVID-19.’ Of the respondents, almost ‘…a third (29%) of Americans became more worried about having obesity…’ with an ‘…estimated 28 million people to explore treatments not considered before the pandemic, including 6.4 million who thought about bariatric surgery or taking prescription obesity drugs.’ This data is particularly shocking, as right now, only about 1% of eligible patients undergo bariatric surgery, with about 1% to 3% taking prescription drugs for obesity, totaling at most 1 million Americans. In relation to the $250B market for diet and behavioral solutions, ‘…three-quarters (73%) consider dieting and exercising to be the most effective method for long-term weight loss…’ though followed by ‘…weight-loss surgery [at] (56%) …’ and ‘…23% deemed taking prescription medications as effective followed by dietary supplements (18%).’ And in furtherance of our biased and polarizing societal narrative, ‘…nearly three-quarters (73%) of those who have tried to lose weight believe obesity is caused by a lack of willpower.’ Wow – we can and must do better for our patients, not only in terms of public information, but to also educate providers who regularly see patients that will likely benefit from high-value obesity care in the form of medication and surgical therapies – yes, I am calling out our primary care physicians, cardiologists, orthopedic surgeons, diabetes specialists, sleep physicians, and infertility experts to name but a few.
  • The US News and World Report, picked up Dr. Kothari’s study, with a quote from the current President of the ASMBS, Teresa LaMasters, a bariatric surgeon in Iowa, who states ‘…Our hope is that people turn the fear of obesity and the consideration of new weight-loss strategies into action…’ and ‘…Americans have more and better options than ever before, and they should take advantage of them when appropriate.’ Dr. LaMasters commits to a call to action for readers of the news story to ‘…Talk to your doctor.’ I hope that Americans do not continue to suffer with the burden of a chronic disease that is treatable through effective multimodal medication and/or surgical therapy, are not resigned to their state as being one of a lack of willpower, but more so a lack of information, access, and widespread availability for all who need treatment, with realized long-term benefits.
  • In a similar phone-based poll of 600 Long Island and city residents, the New York Post reports on eating habits in that ‘Half the respondents admit to binge eating, 60% said they eat two or more fast-food meals per week and 22% said they consume four or more fast-food meals regularly…’ Regarding medical support, only about a quarter of ‘…respondents said they’ve spoken to a medical provider about their weight…’ though one in five ‘…said they would take a prescription drug to lose weight.’ In a nod to Dr. LaMasters, Dr. Adhi Sharma, President of Mount Sinai South Nassau, states ‘I strongly encourage all adults and parents of children who are struggling with being overweight to talk about it with their health care providers…’
  • Novo Nordisk released additional data on their recent evaluation of Rybelsus, a once-daily oral GLP-1 medication, on over 1,200 trial participants with diabetes and an HbA1c of 9% [a measure of blood sugar over three to four months that should be below 6.5% in healthy individuals] and mean weight of just over 96kg, or around 220 pounds. The study compared an approved 14mg dose of Rybelsus, with subjects who were prescribed the newer and higher 25mg and 50mg daily doses, over a very short 28-day period. The reduction in HbA1c was 50% greater in those on 50mg of the drug, compared to those on the 14mg dose – increased from 1.5% to 2.2%; and a doubling of weight loss from 10lbs to 20lbs. So, what does this mean – essentially, that patients who do not achieve control of their diabetes and do not reach target weight reduction, can now go from the currently approved 3mg, 7mg or 14mg doses, up to the 25mg or 50mg daily dosing schedules. And when they do up their doses, there is not an intolerable increase in side effect profile, most of which are GI in nature. Finally, in a presumptive we-told-you-so-don’t-complain-later approach, the press release states that ‘The global roll-out of the 25 mg and 50 mg doses is contingent on… manufacturing capacity.’ in a nod to supply shortages of Ozempic and especially Wegovy during 2022.
  • Viking Therapeutics, a ‘…a clinical-stage biopharmaceutical company focused on the development of novel first-in-class or best-in-class therapies for the treatment of metabolic and endocrine disorders…’ released data this week on VK2735, ‘…a novel dual agonist of the glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors.’ The drug’s dual agonist formulation is akin to tirzetapide, or Mounjaro, currently approved for use in individuals with type II diabetes. The phase 1 study focused upon safety and tolerability of VK2735, with a reasonable side effect profile akin to semaglutide and tirzetapide, with almost 8% of total body weight loss compared to just 2% in control subjects, within 28 days.
  • The press release was covered by Matthew Herper at STAT News, with a note that ‘…analysts and executives expect the market for GLP-1s to become very large – potentially approaching $100 billion in less than a decade…’ and proposing Viking to be a candidate for acquisition, as ‘…an appealing takeout candidate to a company that is missing out on the GLP-1 gold rush or that is unsatisfied with its own R&D efforts.’ One to watch for sure.
  • Similar bullishness is seen from Allison Gatlin writing in Investor’s Business Daily, with the comment that ‘…Viking is going up against diabetes giants Novo and Lilly in obesity treatment.; followed closely by ‘…The market is heating up now with Viking’s results.’

Kind regards, Raj


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