Future obesity treatment may see bariatric surgery combined with medication
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Key takeaways:
- Not all adults with obesity will achieve their target weight loss with medications alone.
- Combining bariatric surgery and medication may confer a greater weight reduction for adults with obesity.
Bariatric surgery will continue to be a therapeutic option for obesity and early diabetes in the future and may be used in combination with newer medications, according to a speaker.
Trial findings have shown that GLP-1 receptor agonists, such as semaglutide (Wegovy, Novo Nordisk) and dual-agonist medications such as tirzepatide (Zepbound, Eli Lilly), can confer weight loss close to bariatric surgery for many adults, but some people may not respond to the drugs, according to Luca Busetto, MD, associate professor in the department of medicine at University of Padova, Italy, and the Center for the Study and the Integrated Management of Obesity at Padova University Hospital, Italy, and vice president of the European Association for the Study of Obesity. Busetto said prescribing medications after bariatric surgery could be the best treatment plan for some people.
“My prophecy is that, in the future, we will see much more combination of bariatric surgery and obesity management medications, at least in people not achieving adequate levels of weight loss with only one of these two arms,” Busetto said during a presentation at the International Conference on Advanced Technologies & Treatments for Diabetes.
Greater weight loss with new drugs
In the Swedish Obese Subjects study published in the Journal of Internal Medicine in 2013, adults who underwent gastric bypass lost more than 30% of their body weight 1 year after surgery and maintained most of that weight loss up to 20 years. Findings from several studies conducted during the past decade have shown that bariatric surgery also provides benefits beyond weight loss, including increased odds for diabetes remission and reduced risks for cardiovascular events and mortality, according to Busetto.
“This is the reason bariatric or metabolic surgery for the last 20 years was clearly the most effective treatment for people with obesity, in particular, people with severe obesity,” Busetto said.
Older obesity medications combined with lifestyle intervention did not yield as much weight loss as bariatric surgery, but newer medications are changing the paradigm, Busetto said. In the STEP 1 trial, 50.5% of adults with overweight or obesity who received semaglutide lost at least 15% of their body weight at 68 weeks, and 32% of the semaglutide group achieved a 20% or greater weight reduction. In the SURMOUNT-1 trial, 70.6% of adults with overweight or obesity receiving 15 mg tirzepatide lost at least 15% of their body weight, and 56.7% achieved a 20% or greater weight loss. In a phase 2 trial, 83% of adults with obesity receiving 12 mg retatrutide (Eli Lilly) lost 15% or more body weight at 48 weeks and 63% achieved a 20% or greater weight loss.
Although the results of the trials are encouraging, Busetto said, medications may not be the answer for all people.
“I personally believe that these important changes in the therapeutic opportunities for treating obesity will not completely reduce the space for bariatric surgery,” Busetto said. “Maybe we can expect that the use of bariatric surgery in people with low BMI can be reduced, but not in the full spectrum of patients with obesity.”
Busetto cited cost and availability of the agents as two reasons medication may not be an option for everyone. Another factor is intolerance or lack of response to the medication.
The solution for some people with obesity may be combining bariatric surgery with pharmacotherapy. A study published in The Lancet Diabetes & Endocrinology in 2019 randomly assigned adults who had persistent or recurrent type 2 diabetes 1 year after bariatric surgery to once-daily liraglutide 1.8 mg (Saxenda, Novo Nordisk) or placebo. The liraglutide group had a greater decline in HbA1c and body weight at 26 weeks compared with placebo.
Another study published in JAMA Surgery in 2023 randomly assigned adults who experienced 20% or less weight loss with bariatric surgery at 1 year to once-daily liraglutide 3 mg or placebo along with lifestyle therapy for 24 weeks. Adults receiving liraglutide lost 8.82% of their body weight vs. a 0.54% weight loss for the placebo group (P < .001).
Busetto said bariatric surgery can lower the risk for all-cause mortality for adults, but prescribing medication after surgery may reduce the risk even further. Data from the SELECT trial published in The New England Journal of Medicine showed that semaglutide was associated with a lower risk of CV events (HR = 0.8; 95% CI, 0.72-0.9) and all-cause mortality (HR = 0.81; 95% CI, 0.71-0.93) than placebo for adults with obesity.
“This raised the possibility that in order to improve life expectancy and to prevent major outcomes like CV events, the combination of bariatric surgery and anti-obesity medication will be the most effective combinations,” Busetto said. “At the end, our aim is not weight loss. Our aim is treat obesity to a target in order to provide benefits.”
References:
Jastreboff AM, et al. N Engl J Med. 2022;doi:10.1056/NEJMoa2206038.
Jastreboff AM, et al. N Engl J Med. 2023;doi:10.1056/NEJMoa2301972.
Lincoff AM, et al. N Engl J Med. 2023;doi:10.1056/NEJMoa2307563.
Miras AD, et al. Lancet Diabetes Endocrinol. 2019;doi:10.1016/S2213-8587(19)30157-3.
Mok J, et al. JAMA Surg. 2023;doi:10.1001/jamasurg.2023.2930.
Sjöström L. J Intern Med. 2013;doi:10.1111/joim.12012.
Wilding JPH, et al. N Engl J Med. 2021;doi:10.1056/NEJMoa2032183.
Perspective
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Despite considerable weight loss of 25% to 30% following bariatric surgery, many patients are not able to achieve remission of their obesity status long term and remain overweight. Insufficient weight loss following bariatric surgery is more common based on baseline severity of obesity, the type of procedure utilized and the presence of obesity-related co-morbidities.
Achieving greater initial weight loss following surgery with use of anti-obesity agents may lead to better long-term metabolic outcomes. Moreover, weight regain is problematic and often requires more aggressive intervention that includes the use of anti-obesity agents in addition to lifestyle measures and addressing psychosocial factors. Weight regain has been associated with worsening of glucose tolerance (such as type 2 diabetes), metabolic dysfunction-associated steatohepatitis, metabolic syndrome and other comorbidities. Data related to the use of anti-obesity agents with GLP-1 receptor agonists has shown additional weight loss in the post-bariatric-surgery population suggesting that the combination of surgery with medications may lead to greater reduction of obesity and its complications in the long term.
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Busetto L. Will new pharmacological treatment for obesity and early diabetes replace bariatric surgery? Presented at: International Conference on Advanced Technologies & Treatments for Diabetes; March 6-9, 2024; Florence, Italy (hybrid meeting).
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