Few public health crises are as crucial for us to solve in the coming decades as obesity. Nearly 800 million people worldwide are living with this condition, which may eventually cause complications and comorbidities such as Type 2 diabetes (T2D), cardiovascular diseases, acute and chronic pain, many types of cancers, mental illness, sleep apnea and osteoarthritis. Every one point above a BMI of 30 is associated with a 2% decrease in income, a 3% increase in social transfer payments and a 4% increase in healthcare costs. Obesity rates are rising as countries develop and food systems adapt—no country has seen a reduction in obesity since the 1970s. Treating obesity effectively means tackling the underlying cause with the best care available.
When a disease afflicts 10% of the world’s population, one would expect global organizations and national governments to mobilize quickly and effectively to tackle it, like we saw with COVID-19 vaccines or when the U.S. launched its “war” on cancer in 1971. The way our society views smoking was radically altered during our effort to bend the lung cancer curve. We addressed the drivers of lung cancer and innovated better diagnosing, screening and treatment tools for it. That we responded to diseases like lung cancer or COVID-19 with global cooperation and funding but have yet to act similarly to tackle obesity illustrates the gaps in our healthcare priorities.
One reason the U.S. has failed to make similar progress on obesity is a lack of safe, effective medications and an incomplete understanding of the drivers that contribute to obesity, among other factors. But recent innovations in life sciences have yielded a class of drugs called glucagon-like peptide-1 receptor agonists (GLP-1s), that can help patients lose between 15%-20% of their weight in about a year and a half by addressing key biological and behavioral drivers of obesity. These medications complement existing surgery and treatment infrastructure in offering patients real solutions. The Food and Drug Administration and other regulatory body guidelines about who qualifies for these drugs are clear. Anyone who has a BMI of 30 or above, or anyone with a BMI of 27 or above plus a weight-related comorbidity like hypertension, diabetes or hyperlipidemia, qualifies for a GLP-1. Medication alone, though, is not a panacea, and we must prepare to treat obesity like we’ve addressed cancer—tackling root causes, better identifying risk and by creating personalized and holistic treatment plans.
We also must acknowledge that one of the biggest barriers to action against obesity is a misalignment across healthcare stakeholders about how to treat obesity as a chronic illness.
Let’s kill the most noxious argument levied by some stakeholders right up front—the notion that obesity is not a disease. While it took the medical community a long time to recognize it, and there remain those unconvinced, major health bodies now recognize obesity as a disease. It’s a disease influenced by a patient’s environment, genetics, socioeconomic status and more. Very frequently, though, healthcare professionals (HCPs) and patients resort to a standard, but ineffective, way to discuss and tackle obesity, if they talk about it at all. In a 2019 study, 71% of surveyed HCPs claimed their patients with obesity were uninterested in losing weight. The same study found that only 7% of patients with obesity reported not being interested in losing weight. In future articles, we’ll talk about ways to make these conversations less uncomfortable for patients and close this gap.
Obesity is an underlying cause of a range of health complications. And it’s a comorbidity of other conditions, such as chronic pain and depression. Yet we still often hear obesity results from behavioral choices—choosing to eat certain foods or choosing to be inactive. The implication being that behavior change trumps clinical action. We treat no other chronic illness this way. Salt consumption can elevate the risk of hypertension and diet influences the development of hyperlipidemia, both of which may lead to major cardiovascular events such as strokes or heart attacks. We may criticize someone who ate very salty food and developed hypertension, or a lifelong smoker who develops lung cancer, but we’ll still treat them with effective medication alongside necessary behavioral changes.
That’s not to say behavioral changes and personal responsibility aren’t a factor in managing chronic illness, of course. Many of us get to make decisions about what we eat, how much time we commit to cooking and what to cook. There are instances where we may have less agency to make decisions, or occasions where socioeconomic status or employment or stress or any number of factors may override our better judgment and steer our behaviors. Rather than focus solely on behaviors, any effective intervention should acknowledge the drivers of disease and address them head on with the most effective options available.
That’s how we tackle chronic illnesses, after all. A crucial first step to treating a disease is acknowledging it’s there. But patients would still need to access the right care to be diagnosed and begin their obesity treatment journey. They’d need to find HCPs who believe that obesity is a chronic illness worth treating. Or, at least, that obesity demands clinical action rather than blaming the patient’s behavior and waiting for them to act. For individuals living with obesity, often, their HCPs, families and friends will need to commit the time to lifestyle modifications, medications, surgeries and other treatments.
The obesity market has a long history of medications promising weight loss but instead delivering safety risks. The fen-phen debacle of the 1990s understandably contributes to HCP and patient hesitations about taking a prescription weight loss medication. But the new GLP-1s and related incretins have given HCPs and patients hope.
GLP-1s and related incretins, which include Ozempic and Wegovy (marketed by Novo Nordisk) or Mounjaro (marketed by Eli Lilly), have been used in some form since 2005. Early GLP-1s were less convenient for patients and required daily injections, but they’ve gotten increasingly easy to administer. We know they aren’t without risks, however, the most common being gastrointestinal side effects. While losing weight is strongly motivating for many, side effects like nausea, which has been documented anecdotally and in clinical accounts, can be discouraging. These risks are manageable for many patients through dose titration schedules and other strategies, but some patients may never truly get over them and might need to cease or change their course of treatment. GLP-1s rarely lead to more severe risks, like pancreatitis, but do have contraindications with certain thyroid issues.
Efficacy is well documented for GLP-1s. This class of drugs offers a host of benefits, such as improving blood sugar control, promoting weight loss and reducing cardiovascular disease risk. But where it truly shines is weight loss.
Early GLP-1s showed promising weight loss between 5%-10% of a patient's weight, and the latest molecules in the class, combined with other incretin hormones like gastric inhibitory polypeptide or glucagon, are leading to weight loss of more than 20%. GLP-1s are also being studied in heart failure, chronic kidney disease, Alzheimer’s disease, liver disease and more. While some of these health benefits remain exploratory, there have been early encouraging signals that this class of medication has wide-ranging positive effects. Anecdotally, we even see signs that these medications may reduce the addictive burden of drinking and smoking.
Compared to earlier advances in obesity medicine, the GLP-1s are truly revolutionary. So far, they’ve proven themselves to be a safer, more effective and more convenient class of drugs compared to precursors. Phentermine and its many derivatives help patients lose, at best, about 5%-7% of their weight but carry risks and are only approved for use for up to 12 weeks. Other drugs, like Xenical, have very complicated dosing regimens that require patients be acutely aware of the caloric and nutritional breakdown of each meal to minimize side effects and maximize efficacy.
In one of the more pivotal trials, patients who stopped Wegovy ended up regaining much of the weight they lost on the drug. Should this be held against the drug and prevent its use? Lifestyle and behavior change is hard—no diet is perfect and adhering to the intense physical activity required for weight loss is a recipe for failure long term. What’s more, obesity correlates strongly with socioeconomic status. Try telling someone who is struggling financially that in addition to working their job(s), caring for their family and stressing out about food, that they should just, well, diet harder. That’s not a very compassionate or effective piece of advice.
Even patients using the clinical gold standard for weight loss, bariatric surgery, experience weight regain or insufficient weight loss requiring further surgery or care. In one of the more famous studies on the matter of lifestyle change, many contestants on the show “The Biggest Loser” ended up gaining back their weight, and more, once they lost the show’s support system. Often, following significant weight loss, our own bodies turn against us as our metabolic rates drop. It can be extremely difficult to reduce caloric intake enough to maintain our new weight.
We don’t usually expect patients with other chronic illnesses to stop taking all medication and treat their disease purely through lifestyle changes. It’s exceedingly rare for a person with T2D or cardiovascular disease to sustain the difficult lifestyle changes to manage their diseases without pharmacological intervention—if they can manage to do that in the first place. We should not expect anything different for patients with obesity.
Any solutions we develop to solve the obesity crisis will require personalized options. For many, that will be some combination of lifestyle modification, medications, surgery and other interventions. Let us consider a patient with obesity who has yet to develop complications but wants to lose weight. They will probably be prescribed some medication, if accessible and affordable, alongside lifestyle modification. For many, significant weight loss creates clear motivation to continue to change habits to maintain it.
But after that? They’ll probably want to reduce their medication burden but will be advised against it given what we know about weight maintenance. So how do we ensure they maintain their weight loss? That’s where personalized planning comes in. Hopefully, throughout treatment, the patient, their family and their HCPs have been working together to build better habits and behaviors to prepare for sustained weight maintenance. In the event of weight regain, the patient always has the option to return to what worked in the past, which is most likely medication in combination with lifestyle modification.
We have failed to develop a scalable solution of this nature in T2D, a disease with many similarities to and overlap with obesity. This is to our detriment. There have been more than 60 medications approved for use in T2D in the U.S. since the early 2000s, but the share of the U.S. T2D population considered at treatment goals has remained flat for much of that time, and now is declining. Weight loss medications are one part of the answer to the larger question of how we solve the obesity crisis, but they cannot be the only answer. We’ll need larger, systems-level changes to food availability, physical activity, built environment and beyond.
We’re now at the point in pharmacological innovation where effective and safe options can be offered to patients with obesity. Any remaining barriers—aside from the significant supply-related issues—for many, are financial and perceptual. The longer the world waits to solve this public health crisis, the more it will cost. We’ve been waging a war on cancer for over 50 years, and while cancer still exists, numerous advances have saved many lives. Obesity is a known threat, yet we’ve responded with uncertainty and hesitation. Improving access to medications and healthier food and encouraging physical activity should be global imperatives that will benefit all of us. We can begin to use the GLP-1s at scale, now, to lower the current healthcare burden caused by obesity. At the same time, we must investigate ways to prevent obesity in the future and look for ways to support patients as they maintain a healthy weight while reducing their medication burden.