‘Obesity is the new hypertension’: The current landscape of pharmacological weight loss
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Key takeaways:
- With realization of the CV benefit of obesity treatment, GLP-1s remain in high demand and short supply.
- Several new drugs for obesity therapies are in later-stage trials, with FDA approval predicted for 2027.
After decades of research, pharmacologic treatment of obesity gained significant traction with the launch of GLP-1 receptor agonists, and several potentially more potent drugs are currently in the pipeline, a speaker reported.
Louis J. Aronne, MD, FACP, FTOS, DANOM, the Sanford I. Weill Professor of Metabolic Research at Weill Cornell Medical College, provided an overview of the current and near future landscape of obesity pharmacotherapies at the Cardiometabolic Health Congress.
“I love telling people that I’ve done more than 60 trials of drugs for obesity treatment in 35 years. It’s only been in the last 2 years that have really moved the needle,” Aronne said during the presentation. “An idea I presented as far back as 19 years ago is that losing weight produces health benefit. Cardiologists have always been skeptical of this. Cardiologists think that being a little bit overweight in [their] studies shows there’s better survival from various cardiac maladies.
“The point is that if you are overweight, you’re more likely to have those problems. We now have, if you will, a dose response of weight loss vs. improvement in obesity comorbidities. And the beauty of treating obesity is that you get all of them,” he said. “For example, if you try to reduce cardiovascular mortality by using a statin, you’re not improving type 2 diabetes. In fact, there’s some areas that may be worse [such as] maybe increasing glucose. If you use a statin, you’re not improving heart failure. But if you get someone to lose weight, you could get all three of those. If you can get 15% or greater weight loss, there’s evidence you could throw type 2 diabetes into remission. You can reduce cardiovascular mortality and improve heart failure, and the list goes on.”
Historically, strategies to treat obesity included diet and lifestyle, orlistat (Xenical, Roche; Alli, GlaxoSmithKline), phentermine, naltrexone/bupropion (Contrave, Currax), phentermine/topiramate (Qsymia, Vivus), endoscopic procedures, lap band, sleeve gastrectomy and gastric bypass, each with increasing proportionate weight loss, according to the presentation.
The more recent drugs, semaglutide (Wegovy, Novo Nordisk) and tirzepatide (Zepbound, Eli Lilly), demonstrated weight loss comparable to bariatric surgery, and also reduced all-cause mortality, HF symptoms, worsening chronic kidney disease, risk for diabetes, BP and triglycerides, according to the presentation. Aronne said with semaglutide now being covered by Medicare for patients after MI and stroke, it would be increasingly difficult for payers not to cover this branch of medicines.
In addition, he said demand for semaglutide and tirzepatide is so great, both drugs are or have been on the FDA shortage list, despite limiting distribution.
“Obesity is the new hypertension, meaning that the treatment of obesity is going to move into the primary care realm. It’s actually moving beyond the primary care realm, where it turns out that 20% of the population is getting one of these drugs, semaglutide or tirzepatide from a medical spa or an online telehealth company,” Aronne said. “The point is that patients want to lose weight. Has anyone ever come in and demanded that you treat their blood pressure, cholesterol or their [chronic kidney disease]? My guess is not. But patients want to lose weight.”
Two new obesity drugs currently in later-stage trials are the combined GLP-1/amylin analog cagrilintide/semaglutide (CagriSema, Novo Nordisk) and the triple GLP-1/GIP/glucagon agonist retatrutide (Eli Lilly).
As Healio previously reported, a phase 2 trial demonstrated a mean 15.6% weight loss and a 2.2% HbA1c reduction among adults with obesity and type 2 diabetes assigned to cagrilintide/semaglutide, and weight loss was superior with the combination drug compared with either of its components alone.
In its phase 2 trial, retatrutide demonstrated an even greater impact on obesity, with patients with type 2 diabetes assigned to the highest dose losing 24.2% of their body weight and improving their HbA1c, researchers reported.
Aronne said with phase 3 data for cagrilintide/semaglutide and retatrutide projected for release in 2026, their FDA approval may be as soon as 2027.
“Over the next couple of years, more and more will be coming out and fitting into various spots in the treatment armamentarium. Think about it. How many drugs are available for hypertension? Over 100 in 10 therapeutic categories. And blood pressure-regulated mechanisms are far simpler than the weight-regulated pathways,” Aronne said. “We’re now finally treating obesity as a disease with this new generation of drugs. The future is very bright. It took 35 years, but we’re finally here.”
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Aronne LJ. Session II: Obesity. Presented at: Cardiometabolic Health Congress; Oct. 17-19, 2024; Boston.
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