Year in Review: Obesity

This year’s headlines featured new FDA approvals, investigational drugs that scored success in major trials, new bariatric surgery benefits, and questions on the clinical utility of body mass index (BMI).

New Approvals, Indications

The start of 2023 came with a new treatment option for kids with obesity, after the FDA late last year expanded the indication of semaglutide 2.4 mg (Wegovy) to include once-weekly treatment for children ages 12 years and up, in combination with diet and exercise.

Underpinning the GLP-1 receptor agonist’s new indication was the phase IIIa STEP TEENS trial where BMI declined an average 16.1% from baseline with semaglutide versus a 0.6% increase with placebo over 68 weeks of treatment. Those on semaglutide lost an average 34 lb compared with a 5 lb gain for placebo participants.

Following a similar path as semaglutide, the diabetes treatment tirzepatide (Mounjaro) gained FDA approval in November for chronic weight management in adults, under the brand name of Zepbound. This injectable is a combination GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist.

Data bolstering the weight-loss approval came from the SURMOUNT-1 and -2 trials. In the first installment, 15 mg of the once-weekly injectable led to an average 18% loss of body weight compared with placebo in people with overweight (BMI ≥27) or obesity (BMI ≥30) without diabetes. As for the second trial, people with overweight or obesity and type 2 diabetes taking the same dose lost on average 12% of their body weight versus those randomized to placebo.

In Development

In an attempt to follow the success of these two obesity injectables, trials of several other investigational drugs were presented at the 2023 American Diabetes Association (ADA) Scientific Sessions.

Achieving the biggest weight loss yet, the investigational triple-hormone receptor agonist retatrutide 12 mg yielded a 24.2% drop in body weight by week 48 of treatment. Lower doses were also associated with clinically significant weight loss. Retatrutide acts as an agonist of GIP, GLP-1, and glucagon receptors. “We have not seen results like this before in a trial of less than 1-year duration with an anti-obesity medication,” said lead study author Ania M. Jastreboff, MD, PhD, of Yale University School of Medicine in New Haven, Connecticut.

Another injectable, survodutide — a combination glucagon/GLP-1 receptor dual agonist — demonstrated a near 15% weight loss with its highest dose (4.8 mg) over 46 weeks. However, a fourth of study participants ditched the drug due to toxicity during the phase II trial.

In another phase II trial, the novel oral nonpeptide GLP-1 receptor agonist orforglipron achieved up to a 14.7% body weight reduction by week 36. Setting this apart from other oral drugs, lead investigator Sean Wharton, MD, PharmD, of Wharton Weight Management Clinic in Toronto, said: “Here’s the good news, it can be taken without restriction of food, water, or other medications.”

And in a phase III trial, a once-daily, high-dose oral pill of semaglutide proved to be just as effective as its injectable 2.4 mg counterpart. In the 68-week OASIS 1 trial, patients taking 50 mg of oral semaglutide lost 15.1% of their weight and had a 34 lb drop in body weight. “These data are very similar to the STEP 1 trial investigating the effect of injectable semaglutide, Wegovy. No big differences,” said Filip Knop, MD, PhD, of the Center for Clinical Metabolic Research at Gentofte Hospital at the University of Copenhagen in Denmark. “Oral semaglutide thus may represent an effective option for the treatment of obesity, particularly for patients who prefer an oral formulation over injectable formulation, but also for clinicians to help them tailor the perfect obesity treatment for their patients.”

Bariatric Surgery Still an Option

Several new studies on bariatric surgery highlighted its effectiveness and wide-reaching benefits. One cohort study found a significantly lower incidence of esophageal, gastric cancer, and overall in-hospital mortality for people with severe obesity who underwent bariatric surgery. Compared with those who opted against surgery, those who had bariatric surgery had a 24% lower risk for these cancers and 40% lower risk for overall mortality.

A similar study reported that female patients with obesity who underwent bariatric surgery had a 36% lower risk of developing a hematologic cancer over subsequent decades compared with usual care.

Another analysis found bariatric surgery in kids with obesity has become more popular in recent years — particularly since a 2019 American Academy of Pediatrics policy statement highlighted the need for increased access. From 2020 to 2021, there was an increase of 18.85% to 24.36% for youths and adults who completed metabolic surgery.

But whether it be in injectable, pill, surgical or lifestyle treatment, new advancements in obesity medicine are crucial as CDC data reported nearly half of U.S. states had an adult obesity prevalence at or above 35% in 2022. Three of these states even had an obesity prevalence of 40% or more.

Shift Away From BMI

While BMI has long been the gold standard to categorizing obesity, some called its clinical accuracy into question this year.

In June, the American Medical Association (AMA) released a report clarifying the role of BMI as a clinical measure, concluding that BMI is inaccurate in measuring body fat in multiple groups because it does not account for the heterogeneity across race/ethnic groups, sexes, and age span. Because of this, the AMA advised clinicians use alternative measures in conjunction with or without BMI for diagnosing obesity.

Shortly thereafter, Aayush Visaria, MD, MPH, of Rutgers Robert Wood Johnson Medical School in New Brunswick, New Jersey, reported at the ENDO 2023 meeting that BMI as a measure alone may have misclassified millions of Americans as not having obesity. “From a clinical, individual patient level, I think it’s the start of the end,” Visaria stated. “I think BMI should be supplemented with other measures.”

Other obesity-related news for 2023 includes:

Is Berberine Really ‘Nature’s Ozempic’?

Medical Spending Higher for Kids Outside Healthy Weight Limits

Regaining Weight After Bariatric Surgery Did Not Lead to Excess Mortality

Semaglutide Plus Cagrilintide Reduced Blood Sugar, Weight in T2D

Trial Supports GLP-1 After Underwhelming Metabolic Surgery

ASA: Hold GLP-1 Agonists Before Elective Surgery

‘Overweight’ BMI Not Tied to Higher Risk of Death, U.S. Data Suggest

ACP Announces ‘Ambitious’ Effort to Improve Access to Obesity Care

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