A question of biology
“Obesity results from inappropriate pathophysiological regulation of body fat mass,” when the body defends adiposity, Dr. 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 U.S. Food and Drug Association 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 (for example, bariatric surgery or liraglutide) versus the percentage of patients that attain the weight losses is roughly bell-shaped, Dr. 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,” Dr. 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.
Dr. Kaplan has reported financial ties to Eli Lilly, Gelesis, GI Dynamics, IntelliHealth, Johnson & Johnson, Novo Nordisk, Pfizer, and Rhythm Pharmaceuticals. Dr. Ryan has ties to numerous Novo Nordisk, Pfizer, and several other pharmaceutical companies, including having an ownership interest in Gila Therapeutics, Xeno Biosciences, Epitomee, Calibrate, Roman, and Scientific Intake.
A version of this article first appeared on Medscape.com.