The future of obesity care: Combination therapy, patient-focused treatment
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An obesity treatment model that utilizes integrated, treatment-focused care and combination therapy when appropriate can enhance patient outcomes without significantly increasing risk, according to a speaker.
Data suggest 46% of U.S. adults meet recommendations for anti-obesity pharmacotherapy, yet just 0.5% of those with obesity are currently treated with medications and 0.25% are treated with bariatric surgery each year, Lee Kaplan, MD, PhD, FTOS, director of the Obesity, Metabolism and Nutrition Institute at Massachusetts General Hospital, said in a key lecture during the virtual ObesityWeek annual meeting.
“We need to individualize care using all the therapies that are available, and we need to move from a treatment-focused approach to a patient-focused approach,” Kaplan told Healio. “That requires thinking about obesity as a disease. When you have obesity, you need to bring to bear all the available tools in ways that are appropriate for any given individual, and it will be different from person to person.”
‘Be flexible to change’
Data from the STEP clinical trial program assessing injectable semaglutide 2.4 mg (Wegovy, Novo Nordisk), published in late 2020 and early 2021, have been described as game changing for obesity management. Approximately 33% of participants assigned semaglutide in the studies lost more than 20% of body weight over 68 weeks. With more drugs in the pipeline promising even greater weight loss, the so-called obesity treatment gap — lifestyle and medications on one end, bariatric surgery on the other — has essentially disappeared, Kaplan said.
Still, Kaplan said, not every participant was a responder to semaglutide therapy, and weight loss with any treatment varies widely. For optimal success in obesity treatment, providers must incorporate heterogeneity of treatment response into any management plan.
“If a medication does not work, you must be willing to try a different medication,” Kaplan told Healio. “If two medications do not work sufficiently alone, it can be worth trying to combine them. When talking about lifestyle, do not assume one size fits all. You must do what we do for all diseases: Take a good history, develop a plan, and if the plan does not work well, be flexible enough to change it or add to it.”
Similarly, bariatric surgery combined with pharmacotherapy can lead to additive weight-loss benefits.
“Bariatric surgery works physiologically, and that provides an opportunity for synergy,” Kaplan said. “We frequently see patients who do not respond to a medication before they get surgery respond to the medication after surgery, even though the surgery already caused substantial weight loss. They are frequently complementary to one another.”
‘Treatment regimens will evolve’
In an ObesityWeek symposium on combination therapy, Nasreen Alfaris, MD, MPH, a consultant endocrinologist and obesity medicine specialist at King Fahad Medical City in Riyadh, Saudi Arabia, said the approach to pharmacotherapy in obesity should mirror the approach in type 2 diabetes — both chronic, progressive, heterogenous, relapsing diseases.
“The way we treat diabetes ... is through escalating treatment,” Alfaris said during a presentation. “Patient treatment regimens will evolve throughout the course of their disease, and this is something in the medical community that we accept and actually embrace. Obesity is no different.”
Pharmacotherapy progression could include medication substitutions, such as swapping a DPP-IV inhibitor for a GLP-1 receptor agonist for a person with type 2 diabetes and obesity, or add-on therapy, Alfaris said. A typical distribution curve will range from non-responders, who experience little to no weight loss, to super-responders, who experience 10% or more total weight loss.
“But what if our patients fall into the area where they lose a little bit of weight, about 5%, but it is not enough? What do we do?” Alfaris said. “What we can do is continue the same drug but add a medication to enhance weight loss and get us to 10% to 20% weight loss.”
Data show different drugs with different mechanisms of action may result in better outcomes in combination compared with use as monotherapy, Alfaris said. In a randomized controlled trial published in Diabetes Care in 2017, researchers analyzed data from 335 adults with obesity and without type 2 diabetes assigned canagliflozin (Invokana, Janssen) 300 mg, phentermine 15 mg, coadministration of both or placebo once daily. At 26 weeks, researchers found combination canagliflozin/phentermine provided more weight loss compared with the individual therapies, as well as superior achievement of weight loss of at least 5% and a reduction in systolic blood pressure compared with placebo.
Alfaris said add-on medication interventions should be considered to prompt weight loss after reaching a plateau or new fat mass “set point,” to induce synergy using multiple agents with different mechanisms of action, and for benefits beyond weight loss, such as type 2 diabetes.
“Avoid the high cost of some drugs by using combinations of other agents, given that obesity, unfortunately, is not covered by many insurance companies,” Alfaris said. “Always remember patient preference; some of your patients will not want to use an injectable drug. You can use multiple therapies in oral form to achieve the same effect.”
Procedural additions
Endoscopic options offer several advantages for adults with obesity who may be poor surgical candidates or do not qualify for bariatric surgery, Reem Sharaiha, MD, MSc, associate professor of medicine and director of therapeutic endoscopy in the division of gastroenterology and hepatology at Weill Cornell Medical College, said during a presentation. Targeted endoscopic therapies, which can include gastric remodeling, outlet obstruction, aspiration and intragastric balloons, are less invasive and less expensive than bariatric surgery and can be repeated or reversed when necessary, Sharaiha said.
Sharaiha noted that approximately 30% of patients who undergo endoscopic sleeve gastrectomy are already prescribed weight loss medications; 25% start weight-loss medications after sleeve gastrectomy. Similarly, medical therapy can provide additive benefits when used with an intragastric balloon, she said.
“Do we add medications? Yes, we do add them for our patients who have devices with less weight loss than desired or for those who want to lose more weight,” Sharaiha said.
Other options can include converting to another endobariatric procedure or to surgery, Sharaiha said.
Patient- vs. treatment-focused care
A person seeking obesity care today will likely find fragmented options for treatment — choices may include a nutrition practice, a bariatric surgery center, a commercial program, an obesity medicine specialist or a primary care provider.
“Where the patient chooses to go for their initial encounter largely determines what kind of treatment they receive,” Kaplan said. “Treatment-focused care is the current standard. The treatment choice is driven by the expertise of the provider who happens to be chosen by the patient. Therefore, the patient is the primary driver of what care they receive.”
In a patient-focused care model, which is the standard of care for most diseases, treatment choice is driven by the best evidence, Kaplan said. Expertise is available to implement or refer for all evidence-based options, no matter where the patient seeks care first.
“Your treatment should not be determined by which phone number you call or which door you knocked on first,” Kaplan said. “Patient-focused care requires recognition and response to obesity as a disease.”
The future of obesity care would best be an integrated system where the engaged primary care provider can refer to and learn from providers in a comprehensive obesity center, whether it is in a single facility or represents a network of contributing practices, Kaplan said.
“This model would facilitate systemwide dissemination of best practices, strategic deployment of limited obesity treatment resources, enhanced and more equitable access to all forms of obesity care, and we would see a more rapid and effective clinical application of research and treatment tools as they emerge,” Kaplan said.
Change the thinking
To optimize obesity care, providers need a shared understanding of the causes, mechanisms, treatments and outcomes of available treatments for obesity, as well as shared understanding of therapeutic goals. That shared understanding does not exist today, Kaplan said.
“We need to make obesity a more dominant focus not only of our attention, but all of our colleagues’ attention,” he said. “The army of people who are going to treat obesity in the long term are going to be primary care providers. First, they need to understand what we know and translate that knowledge to more effective obesity care.”
Clinicians should approach obesity treatment the same way one would approach treating a patient with hypertension, diabetes, or even HIV or Alzheimer’s disease, he said.
“Think how we would discuss, approach, assess and treat these other diseases, and then do it,” Kaplan said. “Do it for obesity, using the full spectrum of tools at our disposal.”
References
Hollander P, et al. Diabetes Care. 2017; doi:10.2337/dc16-2427.
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Kaplan L. What does the future of obesity care look like? Presented at: ObesityWeek; Nov. 1-5, 2021 (virtual meeting).
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