A few weeks ago, I made a patient who lost 100 pounds following a sleeve gastrectomy 9 months prior feel bad because I told her she lost too much weight. As I spoke to her, I realized that she found it hard to make life changes and that the surgery was a huge aide in changing her life and her lifestyle. I ended up apologizing for initially saying she lost too much weight.
For the first time in her life, she was successful in losing weight and keeping it off. The surgery allowed her body to defend a lower body weight by altering the secretion of gut hormones that lead to satiety in the brain. It’s not her fault that her body responded so well!
I asked her to be on my next orientation virtual meeting with prospective weight management patients to urge those with a body mass index (BMI) > 40 to consider bariatric surgery as the most effective durable and safe treatment for their degree of obesity.
Metabolic bariatric surgery, primarily sleeve gastrectomy and Roux-en-Y gastric bypass , alters the gut hormone milieu such that the body defends a lower mass of adipose tissue and a lower weight. We have learned what it takes to alter body weight defense to a healthy lower weight by studying why metabolic bariatric surgery works so well. It turns out that there are several hormones secreted by the gut that allow the brain to register fullness.
One of these gut hormones, glucagon-like peptide (GLP)-1, has been researched as an analog to help reduce body weight by 16% and has also been shown to reduce cardiovascular risk in the SELECT trial, as published in The New England Journal of Medicine (NEJM).
It’s the first weight loss medication to be shown in a cardiovascular outcomes trial to be superior to placebo in reduction of major cardiovascular events, including cardiovascular deaths, nonfatal myocardial infarction, and nonfatal stroke. The results presented at the 2023 American Heart Association meetings in Philadelphia ended in wholehearted applause by a “standing only” audience even before the presentation’s conclusion.
As we pave the way for nutrient-stimulated hormone (NuSH) therapies to be prescribed to all Americans with a BMI > 30 to improve health, we need to remember what these medications actually do. We used to think that metabolic bariatric surgery worked by restricting the stomach contents and malabsorbing nutrients. We now know that the surgeries work by altering NuSH secretion, allowing for less secretion of the hunger hormone ghrelin and more secretion of GLP-1, glucose-dependent insulinotropic polypeptide (GIP), peptide YY (PYY), cholecystokinin (CCK), oxyntomodulin (OXM), and other satiety hormones with less food ingestion.
They have pleiotropic effects on many organ systems in the body, including the brain, heart, adipose tissue, and liver. They decrease inflammation and also increase satiety and delay gastric emptying. None of these effects automatically produce weight loss, but they certainly aid in the adoption of a healthier body weight and better health. The weight loss occurs because these medications steer the body toward behavioral changes that promote weight loss.
As we delve into the SELECT trial results, a 20% reduction in major cardiovascular events was accompanied by an average weight loss of 9.6%, without a behavioral component added to either the placebo or intervention arms, as is usual in antiobesity agent trials.
Does this mean that primary care providers (PCPs) don’t have to educate patients on behavior change, diet, and exercise therapy? Well, if we consider obesity a disease as we do type 2 diabetes and dyslipidemia or hypertension, then no — PCPs don’t have to, just like they don’t in treating these other diseases.
However, we should rethink this practice. The recently published SURMOUNT-3 trial looked at another NuSH, tirzepatide, with intensive behavioral therapy; it resulted in a 26.6% weight loss, which is comparable to results with bariatric surgery. The SURMOUNT-1 trial of tirzepatide with nonintensive behavioral therapy resulted in a 20.9% weight loss, which is still substantial, but SURMOUNT-3 showed how much more is achievable with robust behavior-change therapy.
In other words, it’s time that PCPs provide education on behavior change to maximize the power of the medications prescribed in practice for the most common diseases suffered in the United States: obesity, type 2 diabetes, cardiovascular disease, and hypertension. These are all chronic, relapsing diseases. Medication alone will improve numbers (weight, blood glucose, A1c, and blood pressure), but a relapsing disease continues relentlessly as patients age to overcome the medications prescribed.
Today I made another patient feel bad because she lost over 100 pounds on semaglutide (Wegovy) 2.4 mg over 1 year, reducing her BMI from 57 to 36. She wanted to keep losing, so I recommended sleeve gastrectomy to lose more weight. I told her she could always restart the Wegovy after the procedure if needed.
We really don’t have an answer to this issue of NuSH therapy not getting to goal and bariatric surgery following medication therapy. The reality is that bariatric surgery should be considered a safe, effective treatment for extreme obesity somewhere along the trajectory of treatments starting with behavior (diet, exercise) and medications. It is still considered a last resort, and for some, just too aggressive.
We have learned much about the incretin hormones and what they can accomplish for obesity from studying bariatric — now called metabolic — surgery. Surgery should be seen as we see stent placement for angina, only more effective for longevity. The COURAGE trial, published in 2007 in NEJM, showed that when compared with medication treatment alone for angina, stent placement plus medications resulted in no difference in mortality after a 7-year follow-up period. Compare this to bariatric surgery, which in many retrospective analyses shows a 20% reduction in cardiovascular mortality after 20-year follow-up (Swedish Obesity Study). In the United States, there are 2 million stent procedures performed per year vs 250,000 bariatric surgical procedures. There are millions of Americans with a BMI > 40 and, yes, millions of Americans with angina. I think I make my point that we need to do more bariatric surgeries to effectively treat extreme obesity.
The solution to this negligent medical practice in obesity treatment is to empower PCPs to treat obesity (at least uncomplicated obesity) and refer to obesity medicine practices for complicated obesity with multiple complications, such as type 2 diabetes and cardiovascular disease, and to refer to obesity medicine practices with a surgical component for BMIs > 40 or > 35 with type 2 diabetes, sleep apnea, and/or cardiovascular disease or other serious conditions.
How do we empower PCPs? Insurance coverage of NuSH therapies due to life-saving properties — as evidenced by the SELECT trial — without prior authorizations; and education on how and why metabolic surgery works, as well as education on behavioral approaches, such as healthy diet and exercise, as a core therapy for all BMI categories.
It’s time.
Caroline Apovian, MD, has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, adviser, consultant, or trustee for Altimmune; Cowen and Company; Currax Pharmaceuticals; EPG Communication Holdings; Gelesis, Srl; L-Nutra; and NeuroBo Pharmaceuticals. Received research grant from: National Institutes of Health; Patient-Centered Outcomes Research Institute; and GI Dynamics. Received income in an amount equal to or greater than $250 from: Altimmune; Cowen and Company; NeuroBo Pharmaceuticals; and Novo Nordisk.
A version of this article appeared on Medscape.com.