'If Obesity Were Diabetes or Cancer, How Would You Approach It?'

Marlene Busko

November 04, 2021

Dr Lee M. Kaplan

"When considering the challenges of obesity, ask yourself: 'If it were diabetes, cancer, HIV, or Alzheimer's, how would you discuss it, approach it, assess it, treat it?'" Lee M. Kaplan, MD, PhD, asked the audience of healthcare professionals during this week's virtual ObesityWeek® 2021 meeting.

"And then do it for obesity, using the full spectrum of tools at our disposal," he advised.

This was the takeaway that Kaplan, director of the Obesity, Metabolism, and Nutrition Institute at Massachusetts General Hospital and associate professor, Harvard Medical School, Boston, left the audience with at the end of his lecture entitled, " What does the future of obesity care look like?"

Invited to summarize his main points, Kaplan told Medscape Medical News in an interview that practitioners caring for patients with obesity need to first "recognize that obesity is a disease" caused by dysfunction of the metabolic system that regulates body fat — in the same way immune dysregulation can lead to asthma.

Second, "we are finally developing noninvasive therapies that are more effective," he noted, referring to the recently approved semaglutide, and even more potent weight-loss therapies that could be on the market within 3 years, so that weight-loss outcomes with pharmacotherapy are approaching those with bariatric surgery.

Third, it is important that patients with obesity get "broad and equitable access" to treatment, and healthcare practitioners need to be on the same page and have a "shared understanding" of which treatments are appropriate for individual patients, "just as we do for other diseases."  

Need for a Shared Understanding

Dr Donna H. Ryan

"Dr Kaplan really brought home the idea that we all need a shared understanding of what obesity is — and what it is not," agreed symposium moderator Donna H. Ryan, MD, in an email to Medscape Medical News.

"He underscored the biologic basis of obesity," noted Ryan, professor emerita at Pennington Biomedical Research Center in Baton Rouge, Louisiana, and associate editor-in-chief of Obesity, the official journal of The Obesity Society.

"It is a dysregulation of the body's weight (especially adipose tissue) regulatory system," she continued. "The body responds to powerful environmental pressures that produce excess energy balance and we store that as fat and defend our highest fat mass. This makes obesity a disease, a chronic disease that requires a medical approach to reverse. It's not a cosmetic problem, it's a medical problem," she emphasized.

There is so much misinformation out there about obesity, according to Ryan.

"People think it's a lack of willpower, and even patients blame themselves for not being able to lose weight and keep it off. It's not their fault! It's biology."

Although the supplement industry and fad diets falsely promise fast results, there is no magic diet, she continued.

"But we have made progress based on understanding the biologic basis of obesity and have new medications that offer real hope for patients." 

"With 42% of US adults having a BMI that qualifies as obesity, we need a concerted and broad effort to address this problem, and that starts with everybody on the same page as to what obesity is...a shared understanding of the biologic basis of obesity. It's time to take obesity seriously," she summarized, echoing Kaplan.

A Question of Biology

"Obesity results from inappropriate pathophysiological regulation of body fat mass," when the body defends adiposity, Kaplan explained at the start of his lecture.

The treatment strategy for obesity has always been a stepwise approach starting with lifestyle changes, then pharmacotherapy, then possibly bariatric surgery — each step with a potentially greater chance of weight loss. But now, he explained, medicine is on the verge of having an armamentarium of more potent weight-loss medications.

Compared with phentermine/topiramate, orlistat, naltrexone/bupropion, and liraglutide – which roughly might provide 5% to 10% weight loss, the glucagon-like peptide-1 (GLP-1) agonist semaglutide 2.4 mg/week (Wegovy, Novo Nordisk), approved by the US Food and Drug Association (FDA) in June, provides almost double this potential weight loss.

And two new agents that could provide "never seen before weight loss" of 25% could potentially enter the marketplace by 2025: the amylin agonist cagrilintide (Novo Nordisk) and the twincretin tirzepatide (Eli Lilly) (a combined glucose-dependent insulinotropic polypeptide [GIP] and GLP-1 receptor agonist).

In addition, when liraglutide comes off patent, a generic version could potentially be introduced, and combined generic liraglutide plus generic phentermine/topiramate could be a less expensive weight-loss treatment option in the future, he noted.

One Size Does Not Fit All

Importantly, weight loss varies widely among individual patients.

A graph of potential weight loss with different treatments (eg, bariatric surgery or liraglutide) versus the percentage of patients that attain the weight losses is roughly bell-shaped, Kaplan explained. For example, in the STEP1 trial of semaglutide, roughly 7.1% of patients lost less than 5% of their initial weight, 25% of patients lost 20% to 30%, and 10.8% of patients lost 30% or more; that is, patients at the higher end had weight loss comparable to that seen with bariatric surgery

Adding pharmacotherapy after bariatric surgery could be synergistic. For example, in the GRAVITAS study of patients with type 2 diabetes who had gastric bypass surgery, those who received liraglutide after surgery had augmented weight loss compared with those who received placebo.

People at a cocktail party might come up to him and say, "I'd like to lose 5 pounds, 10 pounds," Kaplan related in the Q&A session.

"That's not obesity," he emphasized. Obesity is excess body fat that poses a risk to health. A person with obesity may have 50 or more excess pounds, and the body is trying to defend this weight.

"If we want to treat obesity more effectively, we have to fully understand why it is a disease and how that disease differs from the cultural desire for thinness," he reiterated.

"We have to keep the needs and goals of all people living with obesity foremost in our minds, even if many of them have been previously misled by the bias, stigma, blame, and discrimination that surrounds them."

"We need to re-evaluate what we think we know about obesity and open our minds to new ideas," he added.

Kaplan has reported being an advisory panel member for Eli Lilly, Gelesis, GI Dynamics, Novo Nordisk, and Pfizer; a consultant for Eli Lilly, Gelesis, IntelliHealth, Johnson & Johnson, Novo Nordisk, Pfizer, and Rhythm Pharmaceuticals; and a stock/shareholder of Gelesis. Ryan has reported being a consultant for Novo Nordisk, Pfizer, Real Appeal, Epitomee, Gila Therapeutics, Xeno Biosciences, Calibrate, Wondr Health, Lilly, YSOPIA, Altimmune, IFA Celtic, Ro, Scientific Intake, Amgen, and Zealand, being on a speakers bureau for Novo Nordisk, having an ownership interest in Gila Therapeutics, Xeno Biosciences, Epitomee, Calibrate, Roman, and Scientific Intake, and being on the SELECT steering committee for Novo Nordisk.

ObesityWeek® 2021. Symposium. Presented November 2, 2021.

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