A renown obesity medicine physician-scientist explains where these new medications fit in and how to manage patients taking them. She also offers tips on weight loss counseling when time is limited.

Gaby Berger, MD, FACP

Gaby Berger, MD, FACP, is a busy Seattle-based primary care physician who regularly sees overweight or obese patients. It’s estimated that more than two-thirds of adults in the U.S. are either overweight or obese. The impact on primary care is substantial, since many of these individuals experience negative consequences that can last a lifetime — and shorten life. Obesity is associated with poor cardiovascular outcomes, metabolic disease, and certain cancers. Its development depends on a complex interplay of multiple factors: genetics, neural pathways, dietary patterns, physical activity.

Berger has witnessed an explosion in the availability and use of anti-obesity medications. She has questions about these drugs, particularly newer GLP-1 agonists. Who should take them, and who shouldn't? How do we manage side effects? What are potential adverse health effects? Berger is also curious to know how the obesity conversation is changing — from measuring adiposity to counseling to goal setting — in light of the emergence of GLP1-agonists. As host of a CME audiocast for primary care clinicians, Berger — who is also Clinical Associate Professor of Medicine at the University of Washington — found an expert to answer her questions.

Fatima Cody Stanford, MD, MPH, MPA, MBA, is an obesity medicine physician-scientist and Associate Professor of Medicine and Pediatrics at Harvard Medical School. She’s one of the most frequently cited scientists in the field, and is recognized for altering the view of obesity as a chronic disease. She fills lecture halls at medical conferences, and speaks directly to the public about obesity, as she did recently on 60 Minutes. Here’s what Berger learned from her conversation with Stanford.

Don’t Just Measure BMI

Stanford says clinicians managing overweight or obese patients should have an understanding of how the body mass index (BMI) measure was derived. Such context can inform counseling and goal setting. In the 1800s, Belgian mathematician Adolphe Quetelet sought to quantify characteristics of the average man and developed the Quetelet Index: weight divided by height squared.

Fast forward to the 1950s, when Metropolitan Life Insurance sought to determine the risk of dying based on weight. The company analyzed primarily white men and women to determine insurability. The term “morbid” obesity was born to describe those in the highest weight class.

In the 1970s, physiologist Ancel Keys built on that earlier work to produce a simplified approach to determining what’s considered “normal.” Keys used height and weight to calculate what he called body mass index.

The problem, notes Stanford, is that medicine and health didn’t factor into the work of Quetelet, MetLife, or Keys. Thus, “when we look at BMI as the sole metric, we’re not looking at the health status of an individual. That’s why I don’t use this tool alone – my patients are not just one number.”

BMI alone fails to capture the range of experiences, particularly in minorities, adds Stanford. “One of the key factors that leads to a higher accumulation of adiposity is stress, trauma, and adverse experiences,” which disproportionately impact the Black, Hispanic, and Indigenous populations. “It's no surprise that we would have higher levels of overweight and obesity within these populations.” 

Counseling Patients: Relapsing Remitting Disease Demands Serious Commitment

Stanford has the luxury of an hour-long initial consult — something most PCPs cannot do. She begins by removing the stigma often attached to obesity. "I say, 'Look, this is not your fault.' I am here to help you deal with how your brain is addressing your weight. I may need to use some tools," including lifestyle and behavioral strategies; anti-obesity medications; and bariatric surgery. She lets her patients know which tools she thinks will work best, but emphasizes that ultimately the decision must be mutual.

Next, Stanford emphasizes that it’s a continuous process. "Obesity is a chronic relapsing remitting disease. It doesn't just go away. The brain is always pulling us back to where it wants to be. There's no magical treatment [despite the availability] of new therapies that show tremendous promise."

Lastly, Stanford makes it clear that the patient is the lead. "I'm the coach but they're the star player – [they have] to be willing and ready to engage."

Counseling On Limited Time: Cut to the Chase, Set a Realistic Schedule

Because PCPs have much less time to devote to patients — typically 15 minutes or less — Stanford suggests they:

• Make sure the patient is ready to make a change. If not, end the conversation
• Ask which weight loss strategies are of interest — lifestyle change, medication, or surgery
• Establish a realistic schedule and support to accomplish weight loss goals

"You're not going to be able to accomplish everything in one short visit," Stanford explains. Nor do it all yourself. Lifestyle and behavioral modifications might require referral to a registered dietitian. Bariatric surgery calls for referral to a tertiary level center. Anti-obesity medications are likely within a PCP's wheelhouse — no referral needed. Understanding the patient's preferred pathway enables you to develop a plan and take the next step, she says.

It may be helpful to send patients a link to Stanford’s video, Obesity: It’s More Complex Than You Think.

Goal Setting: Focus on Metabolic Health Indicators

As for setting a healthy weight goal, it's natural to default to what’s been done for decades: determine how many pounds an individual needs to lose to attain a healthy BMI. But Stanford never sets a weight target. And when patients start to tell her how much weight they want to lose, she playfully covers her ears. "Weight goals are very arbitrary. I do, however, [believe in setting] health goals." She works with patients to set a target waist circumference (a proxy for metabolic health), and monitor cholesterol, blood pressure, liver function, fasting glucose, and insulin levels.

During each visit, "I go through every single lab value with them, [comparing] where they started to where they are now," says Stanford. Patients are often wowed by the improvement. She believes tracking lab values (versus focusing only on total weight and BMI) improves the odds that the patient will lose weight — and be healthier.

GLP-1 Agonists Primer

When anti-obesity medications are the selected strategy, PCPs typically oversee the process. It behooves them to know how the medications work, which are best for specific situations, how to manage side effects, potential adverse health effects, and more.

How They Work

GLP-1 agonists, Stanford explains, upregulate the POMC pathway, "which tells us to eat less and store less," and downregulate the AgRP pathway, "which tells us to eat more and store more." They slow food movement through the GI tract (creating the feeling of fullness longer); increase insulin secretion; decrease glucagon secretion; and increase thermogenesis (leading to calorie reduction).

What to Select For Whom

The two most notable GLP1-agonists are semaglutide (approved to treat overweight/obesity) and tirzepatide (approved for overweight/obesity and type 2 diabetes). Studies show semaglutide — a single-agonist — produces an average of about 15% total weight loss. Tirzepatide — which also includes a GIP agonist — leads to an average of about 22.5% total weight loss. This dual agonist produces both weight loss and better glucose control. "If you have someone who has a problem controlling glucose, worsening diabetes, and higher total body weight, you may need to reach for tirzepatide," explains Stanford. In patients with more modest goals and better glucose control, semaglutide is a reasonable choice.

Managing Nausea

The most common side effects associated with GLP-1 agonists are nausea, vomiting, and abdominal discomfort. Stanford says these effects don’t have to be dose limiting — if they’re well managed. Nausea has been reported most often, experienced by 40-45% of patients as doses increase, she notes. It’s recommended to let at least one month pass before increasing dosage during any point while up-titrating. "But that's the minimum," she says. "Does it make sense to double the dose in a month if the patient is experiencing nausea? Maybe they need two months, or three or four months at the lower dose."

Stanford stresses that being more deliberate with dosing could make a significant difference for patients. "Trials show a 20% reduction in major adverse coronary events from semaglutide. Five-year data shows a reduction in fatal and non-fatal myocardial infarctions and a reduction in stroke." Knowing all this, she says it makes sense for PCPs to mitigate side effects by up-titrating more slowly when necessary, reducing chances that the patient will discontinue use and not benefit.

Monitor Potential Adverse Health Effects

Despite their promise, GLP-1 agonists require diligent monitoring for potential adverse health effects (beyond drug side effects). The most concerning, says Stanford, is loss of muscle mass. She points out that older adults are experiencing significant benefit from GLP-1 agonists. But this group can least afford to lose significant muscle mass, something that concerns Stanford — so much so that she helped author a perspective in JAMA Internal Medicine. “The FDA has been keen to measure fat loss, but we aren’t adequately measuring lean muscle loss. We should be holding pharma accountable [to do] this as they conduct large-scale trials.”  PCPs need to be cognizant of potential bone density changes, loss of muscle mass, and frailty, particularly in older individuals. 

When to Say No

Stanford’s practice is so specialized that she sees only patients with true metabolic health dysfunction. But she knows PCPs are very likely to have patients seeking GLP1-agonists for purely esthetic reasons. “Be very cautious about this – and thoughtful about who really needs these agents,” she warned. “Patients who actually need them can’t get them due to supply chain issues.”

PCPs who use metabolic parameters as their North Star when making decisions about anti-obesity medications will do right by their patients — and the health system as a whole.