Hello everyone, my very best to you this weekend, and I hope you are staying cool in this current heat wave in North America [if you are located here]. Hydrate, hydrate, hydrate!
Overall, this has been a quiet mid-summer week, apart from any of you who celebrated the national day of France this week, July 14th, as the anniversary of the Storming of the Bastille on 14 July 1789, a major event of the French Revolution.
Kind regards, Raj.
AT A GLANCE
- An exclusive from Chad Terhune at Reuters states: only ‘…one-third of patients prescribed a popular weight-loss drug like Novo Nordisk’s Wegovy were still taking it a year later.’
- Boston-based biotechnology company Fractyl Health, focused upon a new approach to the prevention and reversal of type 2 diabetes through endoscopic duodenal mucosal resurfacing, is developing Rejuva, a novel pancreatic gene therapy platform to enable long-term remission of type 2 diabetes.
- Novo Nordisk is primed to launch Wegovy in Germany, its third European foray after Denmark and Sweden, next month.
- Eli Lilly ‘…will buy privately held Versanis for potentially up to $1.93 billion to strengthen its position in the fast-growing market for weight-loss treatments…’ Versanis leads with bimagrumab, a drug that increase muscle while cutting fat, by blocking proteins from binding to receptors called activin type II, with the intent that weight loss is maintained after stopping therapy.
- Lisa Marie Presley ‘…died from small bowel obstruction caused by bariatric surgery, coroner says…’ at the age of 54 years in January of this year.
- Does ‘…Ozempic Use Raises Risk of Suicidal Thoughts’? Based upon a review from Icelandic Medicines Agency, its bigger counterpart, The European Medicines Agency ‘…said Monday it is evaluating the safety risk for patients who take the drugs, manufactured by Novo Nordisk, after learning that three people who took the medicines reported thoughts of self harm or suicide.’
NEWS
- An exclusive from Chad Terhune at Reuters states only ‘…one-third of patients prescribed a popular weight-loss drug like Novo Nordisk’s Wegovy were still taking it a year later.’ Further mention reports on the ‘…annual cost of overall care for patients prior to taking Wegovy or a similar drug was $12,371…’ such that the ‘… full-year cost after starting the medication jumped by 59% to $19,657, on average.’
- Khrysta Baig, a health policy researcher at Vanderbilt University simply states ‘…We need to better target who has access to them if we want to realize their full potential…’ referencing the fact that cost of the intervention needs to align with the value created, in terms of disease remission.
- The reported analysis from Prime Therapeutics, a subsidiary of 19 U.S. Blue Cross and Blue Shield health insurance plans that manages pharmacy benefits for about 38 million people, focused on medical claims data for just over four thousand people with commercial health plans having ‘…received new prescriptions of the drugs from a class known as GLP-1 agonists between January and December 2021, and had a diagnosis of obesity, prediabetes or a body mass index of 30 or higher…’ thus excluding individuals with type 2 diabetes, who generally have highest total costs of care.
- Just 32% of patients were still taking the medication at one year, possibly due to gastrointestinal side effects, but more so based upon ‘…an inability to afford to keep paying co-pays or deductibles.’
- More real world data is going to hit the shores of the GLP-1 medication world, which shall enable us to more fully understand an approach to the right patient, with the right treatment, at the right time, to achieve the desired outcome.
- Boston-based biotechnology company Fractyl Health, focused upon a new approach to the prevention and reversal of type 2 diabetes through endoscopic duodenal mucosal resurfacing, was featured in WIRED magazine on their newest approach…
- Rejuva, a novel pancreatic gene therapy platform to enable long-term remission of type 2 diabetes. Emily Mullin writes on a ‘…one-time gene therapy intended to lower blood sugar and body weight using the same mechanism as semaglutide…’ rather than weekly injections or daily pills.
- CEO Harith Rajagopalan is working on a ‘…one-and-done treatment that would last for years…’ and in essence ‘…deliver an artificial gene to the pancreas that continuously produces the GLP-1 hormone so there’s no need for weekly injections.’
- The Achilles heel, if I may, is how to get the gene into the pancreas. As per Daniel Drucker (an endocrinologist and professor of medicine at the University of Toronto, and a luminary in the anti-obesity medication space): there is skepticism on this approach, noting the ‘…pancreas is a very fragile and important organ…’ and any essence of it being ‘…poked or prodded… can induce inflammation…’ which in my clinical experiences, can be serious enough to be life-threatening.
- An additional concern is the pricing of gene therapies, that can range into the millions of dollars, unaffordable to pretty much everyone apart from the ultra-rich.
- My optimistic mind goes to a vaccine-like approach to obesity, type 2 diabetes and all the comorbidities associated with obesity – right now, this is still in the earliest realm of investigational science, rather than a viable offering for the many tens to hundreds of millions of Americans who suffer daily from the effects of metabolic ill health. And by the way, we already have a one and done approach to obesity and concomitant metabolic disease – highly safe, very effective and low risk – namely gastric sleeve and gastric bypass surgery.
- Novo Nordisk is primed to launch Wegovy in Germany, its third European foray after Denmark and Sweden, next month. The Reuters news story focuses upon supply chain issues in the US, and notes the German residents will receive ‘…the injection pen used in Norway and Denmark, instead of the one deployed in the United States to avoid hitting supplies there.’ The FlexTouch device used in Europe ‘…contains four doses per pen, instead of the one dose in the U.S. pen…’ which is also used for other drugs including insulin and Saxenda, an earlier GLP-1 type medication.
- Eli Lilly ‘…will buy privately held Versanis for potentially up to $1.93 billion to strengthen its position in the fast-growing market for weight-loss treatments…’ as per Sriparna Roy at Reuters. Versanis leads with bimagrumab, a drug that increase muscle while cutting fat, by blocking proteins from binding to receptors called activin type II, with the intent that weight loss is maintained after stopping therapy. This is a big stake in the ground for a drug that is still in phase 2B trial state, and is only going to add more fuel for Novo Nordisk, Pfizer and other big pharma players to source newer drugs in the space.
- Lisa Marie Presley ‘…died from small bowel obstruction caused by bariatric surgery, coroner says…’ at the age of 54 years in January of this year, as per Yahoo! News this week. Sad news indeed. As a practicing surgeon for almost two decades, I know small bowel obstruction to be a rare event following gastric bypass procedures, and exceedingly rare to lead to the death of the patient. My sincere condolences to the Presley family.
- Of grave concern is reporting from Melanie Evans at The Wall Street Journal on ‘…Whether Ozempic Use Raises Risk of Suicidal Thoughts.’ Based upon a review from Icelandic Medicines Agency, its bigger counterpart, The European Medicines Agency ‘…said Monday it is evaluating the safety risk for patients who take the drugs, manufactured by Novo Nordisk, after learning that three people who took the medicines reported thoughts of self harm or suicide.’ It is important to note that past clinical trials on semaglutide have not identified an increased risk of suicide or suicidal thoughts.
OPINION
- Megan Molteni, in the ongoing STAT series on The Obesity Revolution, refers to Anthony Fernandez ‘…among an exploding number of Americans taking these [GLP-1] drugs for weight loss…’ and onward to the ‘…fresh insights into the nature of desire, insights some researchers believe could hold the key for freeing people from all sorts of addiction.’ Food cravings, dopamine, the mesolimbic reward system in the brain, are all mentioned, through to ‘…hot spots of happiness bobbing in a sea of want.’
- Cravings versus appetite, likened to wanting versus liking, are key factors in the approach to desire, and onward to addiction, as per the newer GLP-1 agonists to curb cravings – akin to my past patients who want to eat lettuce and vegetables after bariatric surgery, and have little or no desire to tuck into French fires, hamburgers, or a slice of cheesecake.
- In essence, the ‘…gut and the brain both make GLP-1. In the gut, it regulates metabolism – turning up insulin while dialing down glucagon, a hormone that stimulates the liver to break down carbohydrate stores into glucose. Independently, the brain uses the GLP-1 for other things, like regulating energy homeostasis, activating stress responses, and diminishing reward drives…’ through to ‘…altering the circuitry that drives desire.’
- Of onward concern is ‘…the potential of GLP-1 receptor agonists to muzzle other kinds of motivated behaviors, to act as a sort of excitement extinguisher…’ such that they ‘…wake up one day and realize that they can no longer feel pleasure of any kind?’
- Seven in ten Americans are obese or overweight, leading to an estimated excess 300,000 deaths per year, with extreme obesity lowering life expectancy by an average of 14 years. Importantly, ‘…most efforts to lose weight ultimately fail. Calorie counting and exercise programs can help short term, but most dieters regain nearly all lost weight within a few months – even with help from America’s $150 billion diet industry.’
- Dr. Robert Pearl, in Forbes recounts through the lens of GLP-1 medications, ‘The Ozempic Paradox: Highly Effective But Unaffordable’ in which two competing truths collide. Firstly, ‘…these drugs work like nothing has before… [and] lead to significant and sustained weight reduction…’ and second, ‘…despite the medical opportunity at hand, making these drugs available to all 100 million obese American adults would prove cost prohibitive for businesses, private insurers and the government.’
- Dr. Pearl suggests an approach like Operation Warp Speed, or OWS, that fueled COVID-19 vaccine discovery by a $10 billion upfront investment. Referencing ‘Operation: Slim Provisions’ the author suggests ‘…the government would invest $4 billion up front… [such that] …an entrepreneurial pharma or biotech company could research, develop and patent a rival medication within a couple years.’
- And further, ‘…the company that successfully develops a safe and effective weight-loss drug would be required by contract to sell that medication back to the government for $40 per dose (or $2,000 per patient/year), significantly below the retail price of competing drugs. This would be similar to OWS.’
- I love the narrative, though am unfortunately unsympathetically aligned – mostly in view of the immense lobbying and political bent of the large pharmaceutical companies, who would lose out in this approach. And once again, why are we focused upon a single treatment modality, when we really need to prescribe a whole-person, end-to-end, individualized approach to care, that is by essence multimodal in function.
DATA
- Jennifer Abbasi summarizes the recent weight loss headlines from the ADA meeting in JAMA this week, based upon an interview with Robert Gabbay, MD, PhD, an endocrinologist and the ADA’s chief scientific and medical officer, as well as advisor to Lark Health, Sweetech, Vida Health, StartUp Health and Onduo. Dr. Gabbay’s initial stance is that ‘…before long we’re going to have a number of new options for the treatment of obesity.’
- The article recounts data on the oral version of semaglutide at a higher dose, the effectiveness of tirzetapide on people with obesity and type 2 diabetes, beyond weight loss and inclusive of lowered HbA1c levels, and newer agent retrtutide that has been coined triple-G, with its impact on patients with liver disease.
- In consideration of the role of bariatric surgery, Dr. Gabbay is moderated in his approach, mentioning the ‘…really robust and long-term data on bariatric surgery looking over a 10-year period. So I think surgery will continue to be useful for people, certainly those with very significant obesity.’
- There is mention of head-to-head trials between surgery and medication – whilst I get the scientific nature of these trials, what we need is real world evidence that aligns to the oncology care model – to develop a multimodal approach, that pairs surgery with medication therapy, underpinned by nutrition, behavioral and exercise therapy, in an individualized approach to care, that drives outcomes beyond weight loss, in terms of co-morbidity resolution, and improved physical and mental health.
Kind regards, Raj
