GLP-1 medication mania… the good, the bad and the ugly

NEWS

• Geoff Cook, ‘…co-founder and CEO of the Meet Group, an operator of online dating and social-media apps such as MeetMe, Skout, Growlr and others…’, is taking the helm at Noom.
  • Noom is ‘…best known for offering online coaching and customized health plans to consumers to help them manage their weight and other chronic conditions.’
  • Saeju Jeong, Noom’s founding CEO will become executive chairman, in a Wall Street Journal exclusive as per Chip Cutter. This comes fast on the heels of the announcement of Noom Med, a recently ‘…launched a telemedicine service for obesity care… pairs behavioral-change programs with prescription weight-loss drugs such as Ozempic, Wegovy and Mounjaro for medically eligible patients…’
  • Noom is also not the first company focused upon weight loss and obesity care that has attracted social media talent; Sima Sistani was installed as CEO at WeightWatchers just last year, with past media and social network gigs at Yahoo!, Tumblr and HouseParty.
• Katie Palmer in STAT News reports on TikTok, the social media platform, having suspended dozens of accounts ‘…belonging to content creators who talk about their weight loss and monetize the platform via partnerships with telehealth companies that prescribe GLP-1s and other weight loss drugs.’ Jessica Allen, a TikTok spokesperson, stated ‘…We remove content and ban accounts that promote disordered eating or dangerous weight loss behaviors and do not permit ads for weight loss drugs or supplements…’ Account owners, one of whom is Michael Albert, an obesity specialist and co-founder of Accomplish Health, ‘…expressed frustration over the ban in posts to secondary accounts, pointing out the importance of reducing stigma about obesity treatment on the platform.’
• Global telehealth company Teladoc posted a 10% increase in Q2 revenue, to $652 million, with the share price following to an increase of 9%, from Heather Landi at Fierce Healthcare. Much of this revenue was based upon growth in the direct to consumer mental health segment, though Teladoc is also ‘…eyeing opportunities in the booming weight loss market.’ Announced in April, the program will help members lose wright with ‘…GLP-1 agonists, working in conjunction with other solutions and tools…’ through relationships with employers to manage the costs of GLP-1 medications.
• From Indianapolis, Eli Lilly and Company announced ‘…results of two phase 3 tirzepatide studies in adults with obesity or overweight with weight-related comorbidities, excluding type 2 diabetes.’ The SURMOUNT-3 and SURMOUNT-4 ‘…participants on tirzepatide following intensive lifestyle intervention or with continued tirzepatide treatment, achieved up to 26.6% mean weight loss.’
  • To break this out a little more, SURMOUNT-3 recruited 806 patients, of which 579 achieved greater than 5% total body weight after 12 weeks of intensive lifestyle therapy, and were then prescribed tirzetapide for 72 weeks, with ‘…total mean weight reduction of 26.6% from study entry.’
  • This means that the participants in SURMOUNT-3 were already successful in losing at last 5% of their total body weight with intensive lifestyle therapy, before they began to take the GLP-1 drug. For those on SURMOUNT-4, there was a 36-week period when all 783 enrollees took tirzetapide, followed by a 52-week period during which half were switched to placebo. At 36 weeks, there was 21.1% mean weight loss achieved, which increased to 26.0% at the end of 88 weeks, for those who remained on the drug.
  • Dr. Jeff Emmick, senior vice president, product development at Lilly confirmed ‘…The results of SURMOUNT-3 and -4 showed the highest level of weight loss observed in the SURMOUNT program to date.’
• The launch of Wegovy from Novo Nordisk in Germany is to be limited by high costs, and constrained supplies, as per Karen Gilchrist at CNBC. Emily Field, head of European pharmaceuticals equity research at Barclays, says ‘…Even at current prices in Germany, I still think there will be a decent amount of out-of-pocket demand…’ though tempers this with ‘…very little focus on any of the launches outside the U.S. They’re obviously in a capacity constrained environment and we don’t know how much they’re willing to allocate to Europe.’ The disclosure at the end of the CNBC article importantly notes ‘Barclays is an investor in Novo Nordisk…’ which may color one’s version of the approach taken by Ms. Field.
• The Medicare ban on covering medications for weight loss is under continued fire, by way of the Treat and Reduce Obesity Act (TROA), which was reintroduced to Congress for the seventh time since 2012 on Thursday. The ‘…bill highlights the cost of obesity to the annual Medicare budget…’ such that a beneficiary with obesity has costs of $2,018 (in 2019 dollars) more than a healthy-weight beneficiary. Anjalee Khemlani at Yahoo! Finance continues that Novo Nordisk has reportedly spent ‘…more than $1.3 million on lobbying Congress on various topics, including obesity drugs…’ Robert Wood Johnson Foundation’s Katherine Hempstead says, ‘…feels like there’s an inevitability to this, at some point these drugs will get covered in some ways.’ Past CEO at Jefferson Health and now advisor at General Catalyst Stephen Klasko commented on how GLP-1s have ‘…become a lifestyle drug.’ He continues ‘…If you’re in one of the clubs in Miami, where you used to talk about your plastic surgery, you’re now talking about which GLP-1 you’re on.’
• ‘Nine states from California to Rhode Island have begun to cover expensive, next-generation weight-loss drugs like Novo Nordisk’s Wegovy on their Medicaid preferred drug lists…’ from Ganny Belloni at Bloomberg Law, in reference to ‘… 44% of Medicaid beneficiaries qualifying as obese.’
  • Kate McEvoy, executive director of the National Association of Medicaid Directors sees this as ‘…a growing push from state lawmakers to shift the way Medicaid agencies view obesity…’ in that ‘…obesity is a disease that requires treatment with drugs or other medical measures.’
  • It is with some pride as a Philadelphian to note that ‘…Pennsylvania was one of the first states to embrace the drug, choosing in 2022 to add it to the state’s Medicaid benefit…’ based upon need and to ‘…leverage the Medicaid Drug Rebate Program to allow states to receive significantly higher discounts than private insurers.’
• Madison Muller and Nacha Cattan at Bloomberg note shortages for four of six dosages of Eli Lilly drug Mounjaro, for patients with type 2 diabetes, ‘…showing just how strong demand is for the drug before it even gets formal approval for use in obesity.’ Indeed prescriptions of ‘…weight-loss drugs this year are on track to outpace 2022…’ aligning with market sentiment on a $77 billion projected annual spend by 2030.
• From Maggie Fick at Reuters in London, the Medicines and Healthcare products Regulatory Agency (MHRA), was said to be reviewing safety data on GLP-1 receptor agonists after ‘…some patients reported suicidal or self-harming thoughts, two weeks after similar action by the European Union.’ The review includes semaglutide more commonly known as Ozempic, and liraglutide or Saxenda, both from Novo Nordisk, as well as Astra Zeneca’s exenatide marketed as Bydureon, Sanofi drug lixisenatide known as Adlyxin [no longer available in the US], and Eli Lilly’s dulaglutide or Trulicity. The article notes between ‘…2020 and July 6 this year, the MHRA received five reports of suspected adverse drug reactions involving semaglutide associated with “suicidal and self-injurious behaviour”, via its Yellow Card scheme.’
• ‘Obesity drugs will not join the World Health Organization’s (WHO) latest essential medicines list…’ citing the ‘…uncertain long-term clinical benefit and safety in this patient population.’ In an important comparison, Jennifer Rigby at Thomson Reuters notes ‘…Inclusion on the list can have great significance for access: for example, experts say adding HIV drugs in 2002 helped make them much more widely available to AIDS patients in poorer countries.’

OPINION

• Weight stigma at work ‘…shows heavier people are paid and promoted less than thinner colleagues and are often stereotyped as lazy or undisciplined…’ with 11% of human-resources executives reporting that an applicant’s weight had factored into hiring decisions. Ray Smith at The Wall Street Journal reviews The Hidden Career Cost of Being Overweight, in reference to ‘…weight-related stereotyping or bias…’ and moves in New York City to outlaw weight discrimination at work. The now-buff physiques of tech leaders Jeff Bezos and Mark Zuckerberg are noted, and how ‘…IBM Chief Executive Ginni Rometty recounted how, earlier in her career, when she had put on weight, a boss suggested trimming down would help her get ahead.’ Whilst obesity is not considered a disability, there is a definite overlap between employees who suffer weight discrimination and those who experience discrimination in the form of their age, gender, and race. 
• Taking the model from Netflix subscriptions and applying it to weight loss medications, as a ‘…combination of profits today and number of subscribers for the long term…’ are considered by Gary Cornell at Slate to be the key to ‘…Make Ozempic More Affordable.’
  • The intriguing approach is to focus upon long-term value, in terms of number of subscribers at a lower per unit price, versus shorter-term value creation through higher unit prices for the few.
  • The estimation of savings for six million Kaiser Permanente members with obesity, from a total pool of just over twelve million, is ‘…over $11 billion… in the first year if it could give one of the modern weight loss drugs to all its members with obesity….’ with the giant caveat that ‘…you have to continue giving them the drugs year in and year out.’
  • This approach is firmly aligned with a system of value-based care, where there is less focus on cost of the intervention, and greater intent upon the value created for the population, that sets the price point, to deliver treatment to all who can and should benefit.
• ‘I wish I never touched it. I wish I’d never heard of it in my life…’ is Joanie Knight’s message for anyone considering drugs like Ozempic or Wegovy. Brenda Goodman at CNN Health recounts the experiences of Emily Wright, 38, a teacher in Toronto, Canada who ‘…vomits so frequently she had to take a leave of absence from her job…’ and Brenda Allen, age 42, in Dallas, Texas, who ‘…feels the same way.’ One of mechanisms of action for GLP-1 agonist medications are to slow down transit of food through the stomach, to enable the patient feel fuller longer; a medical condition known as gastroparesis occurs when the stomach does not function to propel food to the small intestine, leading to episodes of nausea, regurgitation and vomiting.
  • Treatments for gastroparesis include medication to enhance gastric propulsion, through to mechanical devices to stimulate the nervous supply to stomach, all the way to surgical remediation.
  • Of noted interest is that gastroparesis is a known complication of type 2 diabetes, one of the main indications for taking a GLP-1 medication. It is though likely that there was an element of gastroparesis in patients prior to taking the anti-obesity medication, that has been exacerbated. ‘They may just be really unlucky…’ is the rather unhelpful comment from Dr. Michael Camilleri, a gastroenterologist at the Mayo Clinic.
  • Of greater value, Dr. Camilleri undertook a clinical study to review stomach function in those taking GLP-1 medications and noted dramatically slowed digestion; it took ‘…70 minutes for half the food they ate to leave their stomachs compared with just four minutes in the placebo group.’
  • In the published clinical studies, around half of all participants reported gastrointestinal symptoms, comprising nausea and vomiting, the majority of of which were mild to moderate in nature. In a statement to CNN, the FDA has ‘…received reports of gastroparesis with semaglutide and liraglutide…’ and ‘…the benefits for diabetes and weight management may outweigh the risks in some patients with gastroparesis or delayed gastric emptying.’
• Dr. Carel Le Roux and colleagues warn on the ‘…excessive unregulated media attention…’ that propagate ‘…the view that there is a magic bullet treatment for obesity…’ this week in The Lancet Diabetes & Endocrinology.
  • Whilst lengthy and complex, the sentence that ‘…Obesity is a chronic and relapsing condition with a complex multifactorial pathophysiology that spans genetics, metabolic maladaptation, neuroendocrine abnormalities, and major shifts in lifestyle, food composition, and societal inequities…’ is just spot on, such that ‘…treatment must be multifactorial, individualised, and adaptable over time…  akin to the accepted approach for other chronic diseases.’
  • And the authors continue with their clarity of words and purpose to state ‘…new medications will neither cure obesity nor render other approaches obsolete, including lifestyle interventions and metabolic surgery.’ Recent clinical trial results for patients on GLP-1 drugs need to be heeded that almost ‘…20% of participants [who] do not experience clinicaly significant weight loss…’ and the ‘…10% of patients will struggle to tolerate the side effects from the medications.’
  • The role of ‘…metabolic surgery for long-term maintenance of weight loss and health gains…’ is promulgated, in light of the fact that ‘…benefits of obesity medications cease if the medications are stopped…’
  • ….with the additional approach of ‘…a healthy lifestyle remains the cornerstone of optimising health.’ Lifestyle therapy and metabolic surgery are valid and effective therapies for obesity, with surgery having shown reductions in ‘…cardiovascular events, microvascular complications, some types of cancer, and all-cause deaths.’
  • ‘…Combining surgical and medical approaches is standard practice in chronic disease management…’ is music to my ears, and sometimes necessary ‘…in the treatment of type 2 diabetes and obesity…’ to achieve ‘…glycaemic control, weight loss, and even reversal of diabetic complications.’
  • The final paragraph says it all… ‘A chronic multifactorial disease requires an approach that is long term, multifactorial, flexible over time, and tailored to the individual. We should not promote one form of treatment by dismissing the other options. We need to combine our efforts and use the right tools, at the right time, and for the right person to achieve optimal care and maximise health benefits for our patients.’
• Dr. Michael Albert, founder and Chief Medical Officer at Accomplish Health, a telehealth medical weight management practice, writes at Medium this week on the prevalence of obesity in the US, such that ‘…by 2030, 80% of US adults will be living with overweight (BMI ≥ 25–29.9 kg/m2) or obesity, while 50% of adults will have obesity.’
  • Moreover, obesity ‘…disproportionately impacts some groups…’ namely lower-income groups, as well as Black and Hispanic adults. The lack of access to treatment, at 2% of all eligible at best, is unacceptable.
  • Telehealth, certainly post-Covid is a viable option to increase access, with opportunities ‘…to improvement appointment adherence and equitable care delivery.’ The costs at around $100 per month to receive virtual-first obesity care ‘…preclude many from benefiting, such as those in disadvantaged neighborhoods who have higher rates of many common chronic diseases…’ and further the silo-based approach to care coordination and integration.
  • Dr. Albert, and I fully agree, believes ‘…modernizing obesity care can best occur through direct integration into the healthcare system…’ which necessitates ‘…tech-enabled care delivery and focusing on partnering with existing stakeholders…’ with the ultimate aim ‘…to deliver equitable, comprehensive, and coordinated obesity treatment.’
• Dr. Daniel Knecht, VP and Chief Clinical Innovation Officer at CVS Caremark, writes ‘The weight loss drug market is exploding…’ though ‘…is most effective when paired with proper dosing and lifestyle support.’ Treatment of obesity ‘…can result in substantial medical cost avoidance in addition to pharmacy spend offsets for health plans and employers…’ through improved management and sometimes cure of chronic diseases such as depression, type 2 diabetes, hypertension, and a reduction in prevalence of certain cancers too. CVS Caremark has ‘…developed a weight management program that integrates high-touch, coordinated care and lifestyle interventions that may include the use of GLP-1s for weight loss…’ comprising member outreach, nutrition and lifestyle coaching, live clinician visits in a virtual setting, dosing adjustments and photo-based food journaling. The employer and health plan-centric ‘…balanced approach to managing cost and care…’ is supported by ‘…a custom Opportunity Analysis [which] can best show a payors’ actual numbers…’ with an intended 2:1 return on investment – impressive stuff if the opportunity analysis is translated to real world data on clinical and financial outcomes of interest.

DATA

• In anticipation on results of the fast upcoming SELECT study with intent to demonstrate a reduction in major adverse cardiovascular events, or MACE, for patients on semaglutide, Xie and colleagues report in The Lancet Diabetes & Endocrinology on ‘… the comparative effectiveness of incident use of SGLT2 inhibitors, GLP-1 receptor agonists, DPP-4 inhibitors, or sulfonylureas on risk of MACE.’ The study is based upon just over 26,000 users of GLP-1 medications, from a total cohort of almost 300,000 participants; there was a 22% lower risk of MACE when compared to standard sulfonylurea medication, or metformin, for patients with chronically high blood glucose levels, such as is seen in those with type 2 diabetes.
• The important and timely BARI-OPTIMISE Randomized Clinical Trial from Dr. Rachel Batterham and colleagues at University College London was published in JAMA Surgery to ‘…assess the efficacy and safety of the GLP-1 receptor agonist, liraglutide, 3.0 mg, on percentage body weight reduction in patients with poor weight loss and suboptimal GLP-1 response after metabolic surgery.’ 70 patients who were at least one year following metabolic surgery, with a suboptimal result of less than 20% total weight loss, were offered GLP-1 drug liraglutide also known as Saxenda, or placebo for a period of 24 weeks, in conjunction with a 500-calorie energy deficient diet.
  • The liraglutide group achieved an additional 8.8% mean body weight loss, compared to just 0.5% in the placebo group.
  • It is critical to note that there was a ‘…range of weight loss responses in [both] the liraglutide and placebo groups…’ ranging from almost zero percentage point weight loss to over 25% in the treatment group; the placebo group experienced a range of 10% weight loss to almost 10% weight gain.
  • In fact, no patient in the liraglutide group gained weight over the course of the trial. Of additional importance, adverse events were ‘…predominantly gastrointestinal, were more frequent with liraglutide…’ at 80% compared to 57% in the placebo group, though there were ‘…no serious adverse events in either group.’
  • This trial will become an important adjunct in the armamentarium of all clinicians who treat patients with severe obesity, and I love the collaborative nature between experts in metabolic surgery, obesity medicine, and biomedical research – true multimodal care.
• It will be of interest and surprise to many that ‘…GLP-1 receptor agonists were first approved for the treatment of type 2 diabetes in 2005.’ Academics from disciplines of law, medicine and pharmacy sought to ‘…analyze how manufacturers of brand-name GLP-1 receptor agonists have used the patent and regulatory systems to extend periods of market exclusivity…’ through review from the FDA and Google Patent, of GLP-1 receptor agonists approved from 2005 to 2021, published in JAMA this week.
  • Of the 10 GLP-1 receptor agonist drugs studied, there were about 19 patients per product, with almost half, or 44% ‘…on the delivery devices rather than active ingredients.’
  • The ‘…median total duration of expected protection after FDA approval… was 18.3 years…’  with market exclusivity ‘…positioned to be longer than other classes of drug-device combinations.’
  • The authors argue effectively that ‘…Lawmakers and regulators should work to develop solutions that facilitate timely entry of generic drug-device combinations for GLP-1 receptor agonists so that manufacturers can earn reasonable returns for limited periods of time, while more patients eventually benefit from lower costs and improved access to these useful drugs.’
• Virta Health, a venture-backed company on ‘…on a mission to reverse type 2 diabetes in 100 million people…’ published a ‘…survey of 80 Chief Medical Officers, Chief Pharmacy Officers and actuarial leaders [that] shines a light on the growing GLP-1 cost crisis.’
  • The key survey findings, introduced by Dr. Adam Wolfberg, Chief Medical Officer at Virta Health, are on diabetes and obesity as the #1 and #2 concerns of health plan leaders, an overwhelming surge in consumer and prescribing in GLP-1s, whose growth will lead to increased spending, referred to as a GLP-1 cost tsumani, and the need for a mix of utilization management strategies.
  • Virta pitches itself as ‘…a drug-free, cost-effective pathway to rapid and sustained weight loss…’ and ‘…provides an off-ramp from GLP-1s to sustained behavior change for members with obesity and type 2 diabetes, alike.’
  • I am all for individualized, whole-person, end-to-end care, underpinned by a multimodal approach – the focus here is upon intensive lifestyle therapy, which will work for some but not everyone.

Kind regards, Raj