In obesity, treat excess weight first to address underlying cardiometabolic disease
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BOSTON — New drugs and devices can reduce weight and weight-related comorbidities, and physicians should optimize therapy choices for patients with several common conditions to reduce their cardiometabolic risk, according to a speaker.
“For many years, I had nothing new to say [about obesity treatment], but I now have some things to say that are going to turn heads,” Louis J. Aronne, MD, FACP, FTOS, DABOM, the Sanford I. Weill Professor of Metabolic Research at Weill Cornell Medical College and director of the Comprehensive Weight Control Center, said during a presentation at the Cardiometabolic Health Congress. “It is very clear that developments in the field of obesity research are going to completely change the way we treat cardiometabolic disease.”
Obesity is a multisystem disease with many complications, yet clinicians have not typically approached the condition as a disease when treating it, Aronne said.
“Wouldn’t it make sense to treat [all the complications] by getting the patient to lose weight?” Aronne said. “The problem has been getting the patient to lose weight. The reason it is so hard is there are physical changes that occur in the hypothalamus and the other parts of the brain that make it difficult for people to lose weight. Patients want to lose weight; they try. But the changes in signaling pathways lead to a rise in the weight set point. Something physical happens that makes it hard for your patients to go back to their original weight.”
Ideal weight loss: ‘We finally have a target’
To improve the comorbidities and complications that often underlie excess weight, it is important for clinicians to understand that there are different dose responses depending on the amount of weight lost, Aronne said. In some cases, such as people with polycystic ovary syndrome or prediabetes, it does not take much weight loss, about 5%, to see a benefit.
“We know 5% weight loss reduces risk for developing type 2 diabetes and 10% weight loss reduces risk by about 80%,” Aronne said. “New guidelines from the American Diabetes Association and the European Association for the Study of Diabetes state that losing 15% of your body weight is a goal, just like glycemic control is a goal. We finally have a target to shoot for that will be seen as equivalent to getting someone’s glucose under control.”
With more weight loss, a patient will see continued benefit, Aronne said.
“Most of these data come from the [bariatric] surgical literature,” Aronne said. “But now we are able to achieve this kind of weight loss with medication. I look forward to being able to conduct randomized trials to test these hypotheses.”
New treatment paradigm
The new paradigm is to treat overweight and obesity first, Aronne said. If the treatment does not address all the complications — dyslipidemia, hypertension, impaired glucose tolerance or overt diabetes — then treat those conditions.
“Instead of the other way around, which is the way it is right now,” Aronne said. “By treating obesity, everything gets better.”
Clinicians should also carefully review a patient’s medication regimen to see if there are changes that can be made by moving away from drug-induced weight gain, Aronne said, adding that weight gain secondary to medications is a potentially modifiable risk. A simple switch from the beta-blocker metoprolol or the selective serotonin reuptake inhibitor paroxetine to more weight-neutral options like carvedilol or fluoxetine can begin to address excess weight for some patients, he said.
Additionally, one antiobesity medication could replace others as weight-related conditions improve, reducing polypharmacy burden. The GLP-1 receptor agonists liraglutide (Saxenda, Novo Nordisk) and semaglutide (Ozempic, Novo Nordisk) are associated with CV risk reduction, Aronne said. Other medications approved for weight loss include short-acting phentermine, phentermine/topiramate, bupropion/naltrexone, orlistat and the new oral hydrogel pill recently approved for adults with overweight and obesity or prediabetes (Plenity, Gelesis).
Titration of any new medication is critical, he said, adding “start low, go slow” to avoid adverse effects like nausea and diarrhea, particularly with a GLP-1 receptor agonist. Discontinue a drug if less than 5% weight loss occurs at the full dose after 3 months.
“We do not give up easily,” Aronne said. “In general, when you add a medication, you can often get additional weight loss, but a key point is not everyone responds. Try a medicine. If it works, great. If it does not, do not keep giving it to the patient. Stop it and do something else. Do not give up.”
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Aronne LJ. Making sense of the evolving treatment landscape in obesity. Presented at: Cardiometabolic Health Congress; Oct. 19-22, 2022; Boston.
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