WOW – what a week! FDA approval for Eli Lilly’s tirzetapide drug, Zepbound; Wegovy cuts cardiovascular deaths by 20%; GLP-1s alone will not solve the obesity crisis; 1/3 less walking activity.
Elaine Chen and Damian Garde at STAT announce the long-awaited approval of Eli Lilly drug tirzetapide, marketed under the name Zepbound, for obesity.
Britney Nguyen at Forbes writesZepbound ‘…could eventually be the best-selling drug of all time…’ in reference to its recent FDA approval.
Pharmaphorum reports on the race to deliver GLP-1 medications to millions who want them. Novo Nordisk is leaving nothing to chance ‘…announcing a plan to spend a whopping DKK 42 billion ($6 billion) to expand its manufacturing capacity.’
‘AstraZeneca is buying its way back into the obesity drug gold rush…’ from Nick Paul Taylor at Fierce Biotech on the Eccogene $185 million for ‘…once-daily drug candidate, ECC5004.’
‘Should we end obesity?’ is the provocatively titled article in TIME this week, from Jamie Ducharme.
Yours truly at twenty30 health writes at MedCity News on ‘Why GLP-1s Alone Cannot Solve the Obesity Crisis.’
Dr. Fatima Cody Stanford and Harvard student Simar Bajaj write in TIME that ‘…Ozempic can’t solve the obesity crisis in America.’
Dr. Michael Lincoff at Cleveland Clinic and colleagues, present at the American Heart Association meeting in my home town of Philadelphia, results of the hotly awaited SELECT study, also known as the Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity trial, supported by Novo Nordisk.
Elaine Chen breaks news of the SELECT study at STAT this morning, with ‘…Novo Nordisk’s obesity drug Wegovy notably cut the risk of heart attacks in a landmark cardiovascular trial that affirms the treatment offers health benefits beyond weight loss.’
In the U.S. ‘…walking activity has declined sharply since the start of the pandemic…’ falling by 36% nationwide, by Linda Poon at Bloomberg.
NEWS
CBS News reports at least ‘…three Americans have been reported hospitalized after using suspected counterfeits of semaglutide drugs…’ according to the U.S. Food and Drug Administration.
A total of ‘…42 reports to the FDA’s Adverse Event Reporting System that mention use of counterfeit semaglutide from around the world…’ with ‘…28 are classified as serious with outcomes that also include deaths.’
In addition, the U.K.’s Medicines and Health Products Regulatory Agency ‘…said it had seized hundreds of potentially fake Ozempic pens since January 2023.’
Eli Lilly released news this week on the U.S. FDA approval of ‘…Zepbound (tirzepatide) injection, the first and only obesity treatment of its kind that activates both GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1) hormone receptors.’
The approval was based on results from the phase 3 SURMOUNT-1 and SURMOUNT-2 trials.
For review, ‘…SURMOUNT-1 recruited 2,539 adults with obesity, or excess weight and weight-related medical problems not including diabetes… taking Zepbound as an adjunct to diet and exercise.’
The treated individuals ‘…experienced substantial weight loss compared with placebo at 72 weeks.
At the highest dose (15 mg), people taking Zepbound lost on average 48 lb.
Mike Mason, executive vice president and president, Lilly Diabetes and Obesity said ‘…Broader access to these medicines is critical, which is why Lilly is committed to working with healthcare, government and industry partners to ensure people who may benefit from Zepbound can access it.’
Elaine Chen and Damian Garde at STAT announce the long-awaited approval of Eli Lilly drug tirzetapide, marketed under the name Zepbound, for obesity.
John Sharretts, director of the Division of Diabetes, Lipid Disorders, and Obesity in the FDA’s Center for Drug Evaluation and Research said ‘…In light of increasing rates of both obesity and overweight in the United States, today’s approval addresses an unmet medical need.’
Importantly, ‘…Zepbound, which targets both the GLP-1 and GIP hormones, has shown up to 21% weight loss in trials.’
It will be sold ‘…at a list price of $1,059.87 per month, about the same price as Mounjaro and about 20% lower than the price of Novo’s Wegovy.’
Based upon supply shortages of competitor drug Wegovy, higher efficacy of Zepbound, and its lower price point, ‘…doctors would likely opt to prescribe Zepbound instead of Wegovy for many patients with obesity – giving Lilly an edge over Novo in the race to dominate what analysts estimate could become a $100 billion obesity market.’
In addition, ‘…regulators in the U.K., where Mounjaro is also approved for diabetes, expanded the drug’s authorization to include obesity.’
Hot off the news of recent approval of Eli Lilly drug Zepbound for weight loss, U.K. Health Secretary Steve Barclay said in a statementrelayed by Reuters that it has the ‘…potential to help thousands of people living with obesity and support those suffering from weight-related illnesses – if used alongside diet and physical activity.’
And further that ‘…Tackling obesity could help cut waiting lists and save the NHS billions of pounds…’ with a cost-beenfit analysis expected to be published in March next year.
Britney Nguyen at Forbes writesZepbound ‘…could eventually be the best-selling drug of all time…’ in reference to its recent FDA approval.
Gina Kolata at The New York Times reviews the FDA approval of Zepbound, as a ‘…a direct competitor to the wildly popular Wegovy.’
Susan Yanovski, co-director of the office of obesity research at the National Institute of Diabetes and Digestive and Kidney Diseases, said ‘…Just a few years ago it would be difficult to imagine two medications like semaglutide and tirzepatide that lead to weight loss that previously was only seen when people had bariatric surgery.’
Karen Weintraub at USA Today notespeople ‘…with obesity now have a second, and possibly a more effective, medication option – if they can afford and access the drug…’ in reference to the FDA approval of Eli Lilly drug Zepbound, or tirzetapide, this week.
Lilly Chairman and CEO Dave Ricks said on the supply shortages that ‘…We’re investing in manufacturing like never before…’ with ‘…help from a new manufacturing facility in North Carolina and expanded production at other sites.’
Dr. Katherine Saunders, an obesity medicine expert at Weill Cornell Medicine described the approval as a ‘…major milestone in the history of obesity medicine.’
Pharmaphorum reports on the race to deliver GLP-1 medications to millions who want them.
Novo Nordisk is leaving nothing to chance ‘…announcing a plan to spend a whopping DKK 42 billion ($6 billion) to expand its manufacturing capacity.’
The ‘…investment will go towards the construction of a new 170,000 sq. m. active pharmaceutical ingredient (API) manufacturing facility…’ though this will not be fast; the facility in Kalundborg, Denmark is not expected to be open until 2029.
The European Medicines Agency ‘…on Friday recommended that the approval of Eli Lilly’s diabetes drug Mounjaro be widened to include obesity…’ as per Andrew Joseph at STAT.
The final decision goes down to the European Commission, which ‘…almost always follows the EMA’s guidance.’
‘AstraZeneca is buying its way back into the obesity drug gold rush…’ from Nick Paul Taylor at Fierce Biotech.
It has agreed to pay Eccogene $185 million for ‘…once-daily drug candidate, ECC5004, into a phase 1 clinical trial in patients with Type 1 diabetes.’
The $185 million upfront is extended by payments of ‘…up to $1.8 billion in future clinical, regulatory and commercial milestones.’
OPINION
Shannon Young at Healthcare Brew profilesElina Onitansky, a bariatric surgery patient and founder of Ilant Health, who wants to partner ‘…with Medicare, Medicaid, and private insurers to provide an affordable, value-based approach to obesity care…’
The startup ‘…publicly launched on October 17 after generating $3 million in funding.’
The approach is to promote ‘…everything from intensive behavioral therapy to pharmacotherapy – including GLP-1 drugs like Wegovy and Ozempic—to bariatric surgery…’ with an intent to become ‘…a single front door for obesity treatment.’
Ilant impressively ‘…employs providers and peer navigators in all 50 states…’ and onward to aggregate ‘…patient information from medical and pharmacy records and uses an algorithm known as Ilant Metabolism Matters to suggest care pathways…’ over two years.
Data and analytics to prescribe a care pathway have been explored across medicine; but we have not seen a translation to robust and durable clinical outcomes.
We need to engage, re-engage, and continually affirm intuitive and timely patient experiences, interactions, and care; to support our highly committed and overworked clinical care providers; to drive clinical care that is accessible, high quality, and cost-effective, over a multi-year period for individuals and broader populations.
A multimodal, whole-person, end-to-end approach for obesity care; for over 100 million Americans, and counting.
‘Should we end obesity?’ is the provocatively titled article in TIME this week, from Jamie Ducharme.
‘Novo Nordisk sold around $14 billion of its various diabetes and obesity drugs in the first half of 2023, and Eli Lilly sold almost $1 billion worth of Mounjaro in a single quarter this year…’ in reference to over ‘…9 million [prescriptions] written in the U.S. in the last three months of 2022 alone.’
Some are uneasy and concerned about the Ozempic tsunami with its ‘…return to an era when thinness and weight loss were unquestioningly valued.’
The U.S. Centers for Disease Control and Prevention, or CDC, is in no doubt that obesity is a ‘…common, serious, and costly chronic disease…’ increasing the ‘…risk of health problems including heart disease, type 2 diabetes, stroke, and certain types of cancer…’ with which I fully agree.
But Ragen Chastain, a certified patient advocate who co-authored a library of Health at Every Size resources, sees Ozempic and the like as ‘…new tools for reinforcing old, damaging body standards rooted in stigma, not science.’
Dr. Caroline Apovian, co-director of the Center for Weight Management and Wellness at Boston’s Brigham and Women’s Hospital is clear in her mind that ‘…Healthy at any size – I don’t even like the connotation.’
Yours truly at twenty30 healthwrites at MedCity News on ‘Why GLP-1s Alone Cannot Solve the Obesity Crisis.’
I begin that ‘…Any siloed approach to weight loss – whether it’s medication, behavioral changes, or surgery – is not the answer…’ and go on to promote ‘…a multimodal and holistic approach… [to] …keep the weight off and support a person’s overall health.’
I wholeheartedly support GLP-1s and applaud their development, as a bariatric surgeon and PhD scientist.
A new lens understands obesity as a disease, not as a character flaw.
We must offer people with obesity ‘…a range of suitable treatments as well: behavioral, nutrition, exercise, medication and surgery, through a coordinated and holistic approach under one roof, with a care coordinator.’
And this aligns so well with cancer care, as a useful model – obesity ‘…is a sophisticated disease and it needs a comprehensive and ongoing treatment model.
GLP-1s may be part of that equation, but they, alone, cannot solve the problem.’
Dr. Fatima Cody Stanford and Harvard student Simar Bajaj write in TIME that ‘…Ozempic can’t solve the obesity crisis in America.’
For sure, diet and exercise are important, but the ‘…the most effective treatments for obesity are interdisciplinary, where this regimen is combined with behavioral therapy, medication treatment, and sometimes metabolic and bariatric surgery.’
Drugs like Ozempic, Wegovy and Mounjaro are ‘…not the panacea the media has made them out to be, and we must resist the temptation to oversimplify the issue.’
In a sentence that aligns fully with our approach at twenty30 health, Stanford and Bajaj want to celebrate ‘…the potential of GLP-1s as part of a comprehensive, individualized, and compassionate approach to treating obesity – one that not only considers individual’s unique needs and circumstances but also focuses on improving overall health and well-being.’ Thank you.
Forbes senior contributor Bruce Japsen notes ‘…Weight loss prescriptions… are driving health costs for employers up by more than $300 per insured worker this year…’ derived from benefits consultancy Aon.
The analysis ‘…comes from its Aon Rx claims data from nearly 500 employers and their 4.4 million health plan members.’
Tracy Spencer, pharmacy practice leader for Aon, said ‘…There is an opportunity to change people’s lives by improving their health. We need to ensure this investment now will result in improved health outcomes which in turn will curtail obesity related medical costs in the future.’
More broadly Aon revealed ‘…average costs for U.S. employers that pay for their employee health costs are projected to rise 8.5% to more than $15,000 per employee in 2024…’ and strikingly that ‘…a full one percentage point of the total cost, or $150, due to GLP-1 drug spending growth.’
Amy Meister, Chief Medical Officer at WW, or WeightWatchers, led a livestream webinar to ‘…dive into third party-validated ROI models for approaching weight health care coverage at an organization.’
The employer-sponsored coverage approach was categorized as offensive ‘…which usually tends to cover anti-obesity medications like GLP-1s…’ and defensive ‘…which leans more conservatively in benefit coverage or addressing new weight treatments.’
DATA
Dr. Michael Lincoff at Cleveland Clinic and colleagues, present at the American Heart Association meeting in my home town of Philadelphia, results of the hotly awaited SELECT study, also known as the Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity trial, supported by Novo Nordisk.
17,604 patients aged 45 years or older with pre-existing cardiovascular disease and BMI of 27 or greater but no history of diabetes, were randomized to almost three years of semaglutide or placebo therapy.
Death from ‘…cardiovascular causes, non-fatal myocardial infarction [heart attack], or non-fatal stroke…’ were 20% lower in those on semaglutide therapy.
Death from any cause was astoundingly lowered by 19%, and non-fatal heart attacks by 28%.
One in six patients had to stop taking the GLP-1 medication, mostly due to gastrointestinal disorders, and overall, one in four patients on the intervention medication stopped taking the drug.
The percentage total body weight loss in the semaglutide group was just shy of 10%, which is lower than in previous trials; likely since the patients did not undergo intensive lifestyle therapy.
But even with a lower degree of weight loss, the outcomes on clinical disease are impressive.
The authors additionally state ‘…Semaglutide improved cardiovascular outcomes in this trial, whereas lifestyle and pharmacologic interventions for overweight or obesity tested in previous trials have uniformly failed to do so.’
The article continues that ‘…bariatric surgery, in which reductions in body weight of more than 20% can be achieved, has been associated with fewer cardiovascular events than usual care.’
In an important statement, ‘…the diversity of the patient group does not duplicate a globally representative population, particularly because only 27.7% and 3.8% of the enrolled patients were women or Black persons, respectively.’
We are in a new era, where obesity is no longer viewed as a failure of willpower; it is a clinical disease, with treatments available that are both life-changing and life-saving.
Additional commentary is provided by Drs. Amit Khera and Tiffany M. Powell‐Wiley from UT Southwestern and the National Institutes of Health, respectively, on the trial publication.
They clearly note the ‘…underrepresentation of Black, Asian, and Hispanic or Latino populations and of women in the SELECT trial…’ such that ‘…future trials should… examine the effectiveness of these therapies according to race, ethnic group, and sex.’
And further on how ‘…the SELECT trial provides a welcome treatment option that can be extended to millions of additional patients…’ in reference to over 20 million Americans with coronary artery disease, the majority of whom are overweight or obese, and 30% with concomitant diabetes.
The challenges of cost and access are considered, whereby treatments ‘…remain effective but underutilized options, particularly for under resourced populations that are disproportionately affected by obesity.’
The closing sentence says it all in that ‘…we must continue to address the upstream underpinnings of obesity and the downstream effects on the communities that are the most vulnerable to the obesity epidemic and have the least access to these new treatment options.’
Elaine Chen breaks news of the SELECT study at STAT this morning, with ‘…Novo Nordisk’s obesity drug Wegovy notably cut the risk of heart attacks in a landmark cardiovascular trial that affirms the treatment offers health benefits beyond weight loss.’
Details of the study were presented in Philadelphia ‘…before a standing-room only crowd – as the first major session of the American Heart Association conference.’
Wegovy did ‘…cut the rate of heart attacks by 28%…’ though we need to be careful to state that the study reported reduced ‘…rate of cardiovascular-related deaths by 15% and strokes by 7%…’ as these latter two data points did not achieve statistical significance.
Chen notes ‘…insurers have been reluctant to pay for the medications, viewing them as cosmetic rather than medical treatments.’
She continues that ‘…SELECT is the first trial to show that an obesity drug improves cardiovascular outcomes, representing a key milestone not only for Novo, but also for the cardiology field…’ to which I would add for the field of delivering care to those who need it.
Whilst insurers balk at the monthly costs of GLP-1 medications, the opportunity to reduce costs within just three years from improved cardiovascular outcomes is tough to negate, which may even lead to coverage for Medicare beneficiaries.
Dr. A. Michael Lincoff, lead investigator of the trial and an interventional cardiologist at the Cleveland Clinic, is quoted ‘…This now establishes overweight and obesity as a new pathway, another modifiable risk factor, that we can treat in patients with cardiovascular disease.’
Additional data, due to the longer term of the trial, out to almost three years, is also compelling in reference to concerns on suicide risk; the trial ‘…found 0.7% of patients taking Wegovy experienced psychiatric disorders, around the same as the 0.6% of patients taking placebo.’
The discussion on whether this is a metabolic versus a weight mediated effect is important; it is both, though my deeper thought is that the former is highly relevant – akin to the impressive resolutions I have seen in patients just a few days following bariatric surgery to dramatically reduce insulin requirements for their diabetes.
Dr. Lincoff similarly concludes ‘…I think it’s a combination of multiple different effects – the magnitude of weight loss, the process and the mechanism by which the weight is lost, and other effects on blood sugar, on inflammation, on blood pressure, and perhaps direct effects of the drug on the heart and blood vessels itself.’
Sue Hughes undertakes a comprehensive and worthwhile review on ‘Final results of the SELECT trial…’ posted on Medscape.
Lead investigator A. Michael Lincoff, MD, at the Cleveland Clinic is quoted ‘…This is a very exciting set of results. I think it is going to have a big impact on a large number of people.’
Lincoff believes ‘…with this new data from the SELECT trial there should be more willingness…’ to have payers reimburse this drug for their beneficiaries.
Dr. Ania Jastreboff, at Yale School of Medicine said the SELECT trial was ‘…a turning point in the treatment of obesity and a call to action…’ with ‘…US individuals meeting the SELECT criteria increased from 4.3 million in 2011-12 to 6.6 million in 2017-18.’
Dr. Michelle O’Donoghue at Harvard Medical School stated the ‘…reduction in events with semaglutide appeared very early after initiation and far preceded the drug’s maximal effects on weight reduction…’ with early evidence that ‘…the drug offers other cardioprotective effects through pathways independent of weight loss.’
As I have maintained over two decades of my clinical practice, weight loss is a part of the story, but the physiological machine of the human body is more responsive that simply weight loss to improve clinical outcomes, through reduced chronic disease burden.
Drs. Monica Gandhi, Kathleen McManus, and Laura Bamford discuss ‘…two studies of the effect of GLP-1 agonists on weight loss in individuals with HIV…’ at MedPage Today.
The studies were presented at the IDWeek meeting in Boston last month; there is a focus on ‘…pros and cons of prescribing these medications in this group.’
Mechanisms of action for intensive calorie restriction, GLP-1 medications and gastric bypass surgery are explored by Dr. Kevin Hall at the National Institute of Health utilizing a ‘…validated mathematical model of energy balance and body composition dynamics was used to simulate mean weight loss trajectories.’
We know well the potency of bariatric surgery of an ‘…intervention magnitude more than 4-fold greater than calorie restriction and about double that of tirzepatide and semaglutide.’
This study points to a ‘…weakened the appetite feedback control circuit resulting in an extended period of weight loss…’ for surgical and medication therapies, as compared to intensive calorie restriction.
In the U.S. ‘…walking activity has declined sharply since the start of the pandemic…’ falling by 36% nationwide, by Linda Poon at Bloomberg, based upon a report from transportation analytics firm StreetLight Data.
Emily Adler, director of content at StreetLight Data and an author of the report stated ‘…What is most notable here is how universal this decline is, though there are geographic distinctions.’
For example, ‘…Metro areas in the Midwest saw the largest decline, with Akron, Ohio, and Louisville, Kentucky, topping the list.’
