Featuring Colin Hamilton, Commodities analyst at BMO Capital Markets, Metal Matters discusses the hot topics in Global Metals & Mining each week. This episode is hosted by Colin Hamilton, Commodities Analyst  In this episode we discuss the new nominal highs for gold, a strong cross-commodity start to Q2, and preview CESCO Week 2024. 13 min. TRANSCRIPT Subscribe to this free podcast and never miss an episode or visit the BMO Equity Research website for more great episodes of Metal Matters.   Podcast disclosure  

  To better understand the advancements in anti-obesity medicine and how treatment and care are adapting to this new opportunity, BMO Capital Markets hosted providers, key opinion leaders, patients, pharmacy benefit managers and biopharma executives at the inaugural BMO Obesity Summit. To kick off the summit, I sat down with Katherine H. Saunders, M.D., Obesity Expert & Co-Founder, Intellihealth. Below is a summary of our conversation.   It wasn’t long ago that many in the medical establishment considered obesity to be a lifestyle problem. A person with obesity was told to eat less and move more, and the weight would simply come off. Of course, if losing weight were as easy as lifestyle modifications, 41.9%1 of American adults likely wouldn’t be living with obesity today. This idea, which dominated obesity treatments for decades, led to patients experiencing all kinds of weight-related bias and stigma as they sought medical care, especially when the person inevitably gained the weight back.  In 2013, however, the American Medical Association voted to classify obesity as a disease,2 the same year the American College of Cardiology, the American Heart Association and the Obesity Society released guidelines3 for comprehensively managing obesity. Since then, there’s been a real evolution in how scientists understand the biological mechanisms behind obesity, leading to a fundamental shift in how care providers think about and treat the disease. From weight gain to chronic medical condition  To treat obesity as a chronic disease, we must understand what’s happening in the body. As a patient gains more weight, inflammation around one particular part of the brain, the hypothalamus, begins to increase. We sometimes call the hypothalamus the body’s energy regulatory center because it’s responsible for maintaining homeostasis, or keeping the autonomic nervous system (including heart rate, body temperature and hunger) in a stable state. When a patient gains weight, inflammation around the hypothalamus prevents certain feedback signals (hormones) from getting through – first, those from the gut that indicate how much food someone has eaten and second, those from fat cells that indicate the amount of fat someone is storing. The result is dysregulated hormonal pathways that make it easier to remain hungry and harder to become full. Unfortunately, this sets many people up for failure when they try to lose weight since it takes more food to feel full at a time when they need to eat less. Walking around in a state of perpetual hunger makes it so much easier to fall off the proverbial wagon while dieting. In addition, each time someone gains back the weight they’ve lost and tries to lose weight again, those dysregulated hormonal pathways get worse, making it even harder to successfully lose weight. So, ironically, weight loss makes it much easier for the body to gain weight.  Treating the disease Like any other chronic disease, obesity is complex and manifests differently in each patient. The good news is that more and more care providers recognize that a multifactorial disease requires a multifaceted response. The last decade has seen the emergence of several different types of anti-obesity medications. Early iterations of these drugs (like phentermine/topiramate and bupropion/naltrexone) netted limited results, with patients losing an average of 5-10% of their total body weight. However, the landscape truly changed with the introduction of GLP-1 – short for glucagon-like peptide-1 – agonists. This class of drugs mimics the hormones our stomachs release when we’re full. Those who take it feel less hungry, feel full faster and stay full for longer. It can be a tremendous relief for anyone who has been fighting against their body’s hunger cues for years, to finally feel satiated.  More recent drugs like tirzepatide and semaglutide show even more promise as alternate pathways to treating obesity.  Misconceptions and the future of obesity treatment  While there are potential side effects to watch for with each type of obesity medication, the stories in the media have largely been overhyped, or lacked context. When a patient takes one of these medications with adequate physician oversight, we’re starting on very low dosing, looking for early warning signs of any side effects and giving medical advice accordingly. For instance, a patient who feels nauseated after eating a certain meal should tell their care provider and a discussion may then happen regarding the foods that the patient should perhaps avoid. Even more common is the misconception that these drugs are a one-and-done approach that patients will be able to stop using once they’ve achieved their desired outcome. As mentioned earlier, obesity is a multifactorial chronic disease, and it doesn’t end with weight loss. Patients should have a team of care providers offering not just prescriptions, but a wide range of support. Maintaining that goal weight requires vigilance, and sometimes medication and lifestyle adjustments.  Ultimately, the biological underpinnings of obesity have crystallized over the last decade, and while weight bias and discrimination still exist in the medical establishment, this disease has become treatable. We have made enormous steps forward in treatment, and this aspect of medical care is vital for nearly half of the population right now. The hope is that these treatments will become more widely available and prescribed in the coming years, so that this chronic disease can be better controlled.  1 https://www.cdc.gov/obesity/data/adult.html   2 https://www.npr.org/sections/health-shots/2013/06/19/193440570/ama-says-its-time-to-call-obesity-a-disease   3 https://doi.org/10.1016/j.jacc.2013.11.004  

  The evolving obesity therapeutic landscape and its potential to help people live longer and healthier lives have captured the public’s attention, but the rapidly developing market for these treatments is far more complex than many investors appreciate.   To better understand the advancements in anti-obesity medicine and how treatment and care are adapting to this new opportunity, BMO Capital Markets hosted providers, key opinion leaders, patients, pharmacy benefit managers and biopharma executives at the inaugural BMO Obesity Summit. The goal of this first-of-its-kind event was to bring together the many constituents in this space, including representatives from Amgen, Structure Therapeutics, WeightWatchers, Intellihealth, Corbus Pharmaceuticals, Altimmune, Terns Pharmaceuticals, Scholar Rock, Prime Therapeutics, Novo Nordisk and Lilly.  Below are five key takeaways from the summit:    1. Obesity is a complex, treatable disease central to many chronic illnesses  In 1994, researchers discovered leptin, a fat hormone critical to a patient’s ability to regulate their body weight, representing a turning point in treating obesity. Put simply, the hormone impairs the brain’s ability to respond appropriately to weight gain. This is important because research shows that cutting out foods doesn’t solve the obesity problem. Rather, chronic inflammation causes irreversible damage that raises a person’s weight set-point – a body’s predetermined weight range. This research provided a framework for treating obesity as a medical condition rather than a lifestyle issue.   Recognizing obesity as a treatable disease was a significant development because it offered a pathway to deal with the growing epidemic. Currently, nearly 40% of Americans are living with obesity, which is tied to more than 200 other chronic illnesses and diseases. Early studies have shown that weight loss of 2% to 5% can deliver measurable benefits for patient health, although losing 15% or more substantially increases those benefits. Select trials have found that some obesity medications have reduced death from any cause and significantly slowed the progress of heart failure and kidney failure. Similarly, blood sugar and type 2 diabetes have been reduced by 73%.   Other potential health benefits have been reported as well, including for chronic kidney disease, obstructive sleep apnea and osteoarthritis, although more research needs to be done.   2. There is room for many players While investors are primarily focused on a pair of high-profile obesity medications, there is room for more players who are differentiated by format, dosing and the comorbidities treated. As some panelists explained, the market needs to understand that obesity medications can work in different ways, similar to how medical advances around cardiovascular outcomes and treatments do. To put that in perspective, there are more than 100 antihypertensive drugs in the market, but only seven for obesity – two of which are combinations of older medications.  Given the prevalence of the disease, there is a considerable need to find scalable solutions, which will create opportunities for additional players, including those using treatments like GLP-1 – the class of popular diabetes medications that have spurred the recent obesity drug conversation – and behavioral-only programs. Some solutions may use both approaches simultaneously, with several panelists noting that behavioral treatments are still relevant when patients are on GLP-1 medications.  As well, solutions must be consumer-centric, be part of a broader approach and address key health challenges. At the same time, they must manage body composition throughout the weight loss journey, as muscle preservation and the quality of weight loss are critical considerations for obesity patients. Behavioral programs are trying to fill this gap by boosting protein for patients on GLP-1. As the market matures, we’ll see greater patient segmentation and differentiation.   3. The future will be combos – and moderation  Like many diseases, obesity will be a lifelong battle for many, requiring regular use of the available medications and treatments. Finding the appropriate dosage for patients remains a key focus. In some cases, patients are responding by eating too little, which requires a plan to reduce the dosage and slow the rate of weight loss while changing other behaviors, such as diet, supplements and exercise. Taking medications every week, for instance, may not always be necessary.  As much as the new medications might be seen as a game-changer for the treatment of obesity, no one solution on its own will end the epidemic. The future will be a mix of therapies and personal lifestyle choices. Some combinations could include drugs that prevent muscle mass loss, such as myostatin inhibitors and selective androgen receptor modulators, while also reducing appetite.  4. Insurers must evolve to help patients gain better access to treatments  While health insurers are adapting to these new medications, coverage remains limited. Costs are high for all new medications, but especially for those in high demand and tight supply, and manufacturing and capacity for these drugs are expected to remain a key constraint for two years. However, insurers will have to consider the impact these medications could have on coverage costs longer term, especially as more data around other positive health outcomes comes to light. Today, some patients report waiting up to eight months to get an appointment with an obesity specialist. In time, coverage will likely be determined by genetic analysis or comorbidities. Insurers must also prepare for an influx of claims, as patient enthusiasm for new treatments is likely underestimated. The current stigma around obesity is one of the few barriers remaining when it comes to access and having a broader understanding of the potential for these therapies. Those on Medicare will also have a challenge with coverage – and it doesn’t appear as though that will soon change. Still, in the interim, the impact on providers may be minimal as patients have shown a willingness to pay out-of-pocket.  5. Weight bias, stigma and discrimination remain a challenge Despite the promising health benefits of these drugs, there is a stigma around obesity medications, with many thinking patients are taking the easy way out. To get past this view, patients and providers must see obesity as the disease it is rather than as a vanity project. Now that the door is open for pharmaceutical firms to enter this sought-after market, it’s created a bit of a Wild West scenario, said some of the panelists. Against this backdrop, it’s even more important for providers to take a science-based approach when prescribing these medications. Consumers and providers need more awareness of the different treatment options. Even with these new tools, for many patients, obesity will be an issue for the rest of their lives. The current medications and behavioral therapies will help manage the disease, not cure it. More research needs to be conducted to identify any potential long-term side effects from these meds, especially as patients may need to take the medication forever.  

  As a leading non-profit solar installer in the United States, GRID expands access to solar power through community-focused programs.  In this Sustainability Leaders episode, Melissa Fifield sat down with Erica Mackie, Co-Founder and Chief Executive Officer, GRID Alternatives to learn more and discuss the importance of offering “energy for all.”   Sustainability Leaders podcast is live on all major channels, including Apple and Spotify.