Procedure evolution, data growth boost success of bariatric, metabolic surgery
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During the past 20 years, Endocrine Today has reported on advancements in bariatric and metabolic surgery, including the evolution of the procedure and growth of high-quality clinical trial data documenting efficacy and safety.
There have been dramatic changes in procedures, goals and outcomes of bariatric and metabolic surgeries during the past 2 decades, Anita P. Courcoulas, MD, MPH, FACS, chief in the division of minimally invasive bariatric and general surgery at University of Pittsburgh, told Endocrine Today.
Photo courtesy of Santina Wheat. Printed with permission.
“We have seen a dramatic procedure evolution throughout the life span of bariatric surgery,” Courcoulas said. “The procedure has shifted from bariatric to metabolic — from treating patients to help with excess weight and severe obesity to moving toward treating metabolic diseases, including diabetes and hyperlipidemia.”
Perhaps the most impressive change in the field of bariatric and metabolic surgery, Courcoulas added, has been the tremendous growth in high-quality, long-term outcomes research.
“These outcomes have been carefully studied all over the world,” she said. “We now have large, randomized and observational studies that have shown the effect of the procedures on health outcomes and quality of life.”
Another substantial change in the past 20-plus years is that surgeries have become minimally invasive, Philip Schauer, MD, FACS, FASMBS, professor of metabolic surgery and director of the Bariatric and Metabolic Institute at Pennington Biomedical Research Institute at Louisiana State University, told Endocrine Today.
“Going back to the early 2000s when laparoscopic bariatric surgery was beginning to grow dramatically, that is what really changed ‘the game’ because it allowed these operations that otherwise required a very large incision to be done with very small incisions. This less invasive approach dramatically reduced pain, recovery time, hospital stay, costs and complications associated with the surgery,” Schauer said. “Moreover, the field of bariatric surgery was relatively small 20 years ago and high-quality data had not yet surfaced. We now have high-quality data and have been able to document all the presumed benefits of bariatric surgery.”
Landmark clinical trials
The 2007 landmark Swedish Obese Subjects study showed bariatric surgery led to long-term weight loss and decreased overall mortality among patients with severe obesity compared with standard medical treatment.
“The Swedish Obese Subjects study had a significant impact on the field. It was a large study and was powered sufficiently to look at clinical outcomes, including heart attack, stroke and death,” Schauer said. “The researchers also documented reductions in microvascular complication rates after surgery compared with medical management among those with diabetes included in the study.”
However, the trial did have its limitations, according to Schauer.
“For one, the study was not a randomized trial, and there were potential biases,” he said. “Since that study, however, there have been about 30 other observational, nonrandomized clinical trials that corroborated the major reductions in cardiovascular morbidity and mortality.”
Ten years after that landmark study, Schauer and colleagues reported on 5-year results of the Surgical Treatment and Medications Potentially Eradicate Diabetes Efficiently (STAMPEDE) trial.
Results showed bariatric surgery plus intensive medical therapy was more effective than intensive medical therapy alone among 150 patients with type 2 diabetes and a BMI between 27 kg/m² and 43 kg/m².
“STAMPEDE was specifically conducted in people with advanced type 2 diabetes who were moderately overweight,” Sangeeta R. Kashyap, MD, physician scientist in the Endocrinology Institute at Cleveland Clinic, professor of medicine at the Cleveland Clinic Lerner College of Medicine and Healio | Endocrine Today Co-editor, who was an investigator for the trial, said during an interview. “Results showed remission in about 30% of patients at 5 years, and 90% of patients were able to discontinue insulin. That was huge. We have not had another treatment do that and suggests that this may lead to regression of disease and its complications as well as improved quality of life.”
STAMPEDE was the first, and remains the largest, randomized controlled clinical trial to compare bariatric surgery plus intensive medical therapy vs. intensive medical therapy alone.
“Our study showed bariatric surgery was superior to intensive medical therapy in terms of glycemic control and also rendered a number of patients in complete remission of their diabetes,” Schauer said. “Other benefits included improvements in dyslipidemia and hypertension and many other biomarkers of inflammation. Quality of life was also superior in the surgical group. Since that trial, there have been at least 10 other small randomized controlled trials that corroborated our results.”
In addition, one randomized controlled trial published in 2021 in Lancet demonstrated superiority of surgery over medical therapy for diabetes over a 10-year follow-up period. The combined findings of these trials and others led to new guidelines for diabetes treatment.
“In 2016, the American Diabetes Association added metabolic surgery as a treatment option for diabetes,” Schauer said. “The new recommendations were based on data from the Swedish Obese Subjects study, the STAMPEDE trial and others. These studies have truly changed clinical practice.”
Based on the results of these studies, the American Society for Metabolic and Bariatric Surgery and the International Federation for the Surgery of Obesity and Metabolic Disorders also updated the 1991 NIH consensus statement on bariatric and metabolic surgery. They recommended that even for patients without metabolic disease, weight-loss surgery should be considered for those with a BMI of 30 kg/m² who have not achieved substantial weight loss with nonsurgical medications. Moreover, surgery should be considered starting at a BMI of 27.5 kg/m² for Asian Americans.
“There was a shift in the procedure from a weight loss/bariatric operation to also a metabolic operation and in the indications for surgery where people with class 1 obesity and a BMI between 30 kg/m² and 35 kg/m² with uncontrolled diabetes could be considered for surgery to treat their diabetes,” Courcoulas said.
Effect on other comorbidities
Bariatric and metabolic surgeries also have significant effects on risks for cardiovascular disease, nonalcoholic steatohepatitis (NASH), arthritis and cancer.
“We know that patients with severe obesity on average live about 8 to 9 years less than those who have normal body weight, but we have also learned that if we help patients lose a large amount of weight many of the conditions associated with obesity are reversible and the life span will increase,” Ali Aminian, MD, FACS, director of the Bariatric and Metabolic Institute at the Cleveland Clinic and professor of surgery at the Cleveland Clinic Lerner College of Medicine, told Endocrine Today.
“Between 80% and 90% of patients with diabetes go into remission after bariatric surgery, and between 40% and 50% of patients remain in remission long term,” Aminian said. “These patients go on to have normal blood glucose, which is important because that decreases the risk for end organ damage from diabetes, the risk for heart disease, retinopathy, kidney damage and neuropathy — all of these comorbidities can be lessened by bariatric surgery.”
The risk for CVD is also greatly reduced following bariatric surgery, Aminian added.
“When patients lose weight after surgery, there is less workload on the heart, and the risk for future heart attacks is reduced up to 40%, the risk for future heart failure decreases between 50% and 60% and the risk for future stroke is decreased up to 30%,” he said.
Obesity is also a significant driver of fatty liver disease and NASH.
“There is currently no FDA-approved treatment for NASH — the current NASH treatment guidelines recommend is is weight loss,” Aminian said. “Patients need to lose large amounts of weight, and currently bariatric surgery can provide that magnitude of weight loss needed to reverse the course of NASH.”
Bariatric and metabolic surgeries also reduce cancer risk.
“It is estimated that by 2030, obesity will be the most common preventable cause of cancer in the United States,” Aminian said. “We know that obesity is linked to at least 13 different cancer types. If a patient undergoes bariatric surgery and loses weight, then the risk for cancer decreases up to 40% and the risk for cancer-associated death is also significantly decreased.”
COVID-19 outcomes also appeared to lessen among patients who have undergone bariatric surgery.
In a study published this year in JAMA Surgery, Aminian and colleagues found that patients who underwent bariatric surgery years prior to a COVID-19 infection experienced better outcomes after contracting the virus compared with patients with obesity who did not undergo bariatric surgery.
“Patients with obesity who contracted COVID-19 had a greater chance of being admitted into the hospital, a greater chance to be placed in the ICU or require mechanical ventilation and were at increased risk for death from COVID-19,” Aminian said. “The risk for hospital admission, for developing a severe form of COVID-19 and requiring oxygen were all significantly reduced among patients who underwent bariatric surgery compared with patients who were obese at the time of a COVID-19 diagnosis.”
Collectively, the available data indicate that if patients lose weight, the health consequences of obesity can be reversed and even prevented, Aminian said.
“We need to work with primary care physicians and other health care providers to take obesity seriously because it is linked to so many other medical conditions and is a major risk factor for many comorbidities,” he said. “Obesity is reversible and modifiable. We just need to address it.”
Ongoing research
Ongoing research indicates a link between bariatric surgery and the effect on the intestine and the way it regulates glucose metabolism.
“The success of bariatric surgery and the parallel success of medical therapies targeting GLP-1, such as semaglutide (Wegovy, Novo Nordisk), or dual GLP-1 glucose-dependent insulinotropic polypeptide (GIP) agonists have highlighted that the intestine and its production of hormones is an important regulator of whole-body metabolism — especially glucose and lipid metabolism,” Mary-Elizabeth Patti, MD, principal investigator at Joslin Diabetes Center, director of the Hypoglycemia Clinic and associate professor of medicine at Harvard Medical School, told Endocrine Today.
More specifically, surgery-induced alterations in gastrointestinal anatomy and the resulting changes in nutrient delivery to the intestine and intestinal hormone secretion are thought to be major contributors to the profound and durable effects of surgery on both body weight and metabolic diseases, Patti said.
“This is remarkable and certainly underscores the fact that targeting the intestine is important and has facilitated the development of new therapies for obesity, weight loss and diabetes management,” she said. “There’s also ongoing research examining new therapies that may harness the beneficial effects of bariatric surgery, such as the luminal resurfacing approaches that can be done endoscopically and other potential luminal-directed treatments that could be taken orally to stimulate the same hormonal responses engaged by bariatric surgery.”
Research is also ongoing to assess the mechanisms by which some develop hypoglycemia after surgery, according to Patti.
“We received grant funding to examine the various factors that contribute to the development of hypoglycemia in patients, with the goal of developing new approaches to prevention and treatment of hypoglycemia, not only after bariatric surgery, but also in patients who develop hypoglycemia without undergoing surgery,” Patti said.
These same mechanisms may be important for lowering glucose in patients with type 2 diabetes, opening up new approaches to treatment, Patti said.
The field of endobariatrics, which includes intragastric balloons, gastric aspiration therapy and endoscopic sleeve gastroplasty, is another area under development in clinical trials.
“Another innovation in the field is developing less-invasive procedure options,” Courcoulas said. “The endobariatric procedures are intermediate procedures because they are on the spectrum between behavioral weight control and surgery and are less invasive. Endobariatric procedures have grown tremendously, and the field is beginning to develop more long-term and high-quality studies to assess the durability of the impact on weight and metabolic conditions over time.”
Future appears bright
Experts unanimously agreed that the future of bariatric and metabolic surgeries appears bright.
“The field is coming to address some of the up-to-date, modern, fundamental issues with bariatric and metabolic surgeries, including how to best deliver more precise surgical treatments,” Courcoulas said. “But if we are going to operate on a patient, we need to know if they are going to respond well. We need more knowledge around the predictors of surgical outcomes and what the biologic predictors are. We need to learn how to better characterize phenotypes and personalize surgical treatments.”
Despite the successes of bariatric and metabolic surgeries, Kashyap said the procedures are still not being used as often as they should for those with unmet needs.
“There are many patients who are not improving [on medication], but physicians are not referring them to even consider [bariatric or metabolic surgery] as an option,” she said. “The field has evolved where the surgery is minimally invasive and recovery time is improved. It is a treatment for type 2 diabetes, fatty liver disease and even polycystic ovary syndrome — many women have been able to get pregnant who could not. It is still underutilized, but the community is more aware of the procedure because of the studies that have come out and the level of evidence to support use.”
Schauer agreed.
“Only 1% of individuals eligible for metabolic surgery actually undergo the procedure. I feel very fortunate to have been a participant in the incredible development of this field and to witness its growth. However, one thing that is missing is the adoption rate,” Schauer said. “Even though metabolic surgery is recommended by the American Diabetes Association, the adoption rate has lagged. Part of that is because U.S. insurance companies do not always include it as a benefit, which is a source of tremendous frustration not only by surgeons, but patients and even referring physicians, because the evidence of the effectiveness is so solid.”
Moving forward, Aminian said, an individualized approach to treatments is key.
“Obesity is a chronic progressive disease and when a patient has obesity, they need lifelong help to treat their disease of obesity,” he said. “In the future, we will have more effective medications and so a combination of medication and surgery may help some patients. There may also be certain patients who benefit most from one procedure over another, so if we have biomarkers to identify which procedure type would benefit a particular patient that will be helpful. We will have this type of research in the future, and it will hopefully change the field.”
Patti said the field will see continued development of less-invasive procedures, such as endoscopic procedures that target the proximal intestine.
“We will also see improvements in our understanding of better ways to manage long-term nutrient deficiencies that occur after bariatric and metabolic surgeries,” Patti said. “It is important that physicians and patients alike understand that it is a lifelong treatment, and we need to continue to follow-up with our patients to ensure that their vitamins and minerals and overall nutrition are optimal. We also need to improve access to bariatric and metabolic surgery across all socioeconomic groups. There are certainly great disparities in who undergoes these procedures, so understanding why that is and how we can correct it is another important goal.”
- References:
- American Diabetes Association Professional Practice Committee. Diabetes Care. 2022;doi:10.2337/dc22-S008.
- American Society for Metabolic and Bariatric Surgery. After 30 years — new guidelines for weight-loss surgery (press release). Available at: asmbs.org/articles/after-30-years-new-guidelines-for-weight-loss-surgery. Published Oct. 21, 2022. Accessed Nov. 7, 2022.
- Aminian A, et al. JAMA. 2022;doi:10.1001/jama.2022.9009.
- Mingrone G, et al. Lancet. 2021;doi:10.1016/S0140-6736(20)32649-0.
- Schauer PR, et al. N Engl J Med. 2017;doi:10.1056/NEJMoa1600869.
- Sjostrom L, et al. N Engl J Med. 2007;doi:10.1056/NEJMoa066254.
- For more information:
- Ali Aminian, MD, FACS, can be reached at aminiaa@ccf.org; Twitter: Ali_Aminian_MD.
- Anita P. Courcoulas, MD, can be reached at courcoulasap@upmc.edu.
- Sangeeta Kashyap, MD, can be reached at sangeetakashyap857@gmail.com.
- Mary-Elizabeth Patti, MD, can be reached at maryelizabeth.patti@joslin.harvard.edu.
- Philip Schauer, MD, can be reached at philip.schauer@pbrc.edu.
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