CHICAGO—In patients with obesity and metabolic dysfunction–associated steatotic liver disease, treatment with endoscopic sleeve gastroplasty led to more weight loss and significantly greater improvements in hepatic steatosis index than treatment with the glucagon-like peptide-1 agonist semaglutide.
A large majority of patients with obesity—some studies have found up to 90% of patients—also have metabolic dysfunction–associated steatotic liver disease (MASLD), formerly called nonalcoholic fatty liver disease, and the primary treatment recommendation is weight loss (Gastroenterology 2012;142[7]:1592-1609). Both ESG and semaglutide are effective in producing and sustaining weight loss, but the question is—which is better not just for weight loss but also for improving liver disease parameters, said senior investigator Reem Z. Sharaiha, MD, MSc, the director of interventional endoscopy at NewYork-Presbyterian/Weill Cornell Medicine, in New York City.
Dr. Sharaiha and her co-investigators tackled this question via a retrospective analysis of patients with MASLD and diabetes treated with these approaches at Weill Cornell Medicine, presenting their findings at the Digestive Disease Week 2023 (abstract 455). “Our study is the first matched analysis between these groups, and it demonstrates that multimodality treatment may be useful for treating [MASLD] and obesity,” she said.
Established Benefits of 2 Approaches
In previous studies, Dr. Sharaiha’s team demonstrated the value of ESG in producing total body weight loss (TBWL) averaging 16% at five years and significant improvements in liver enzymes, hepatic steatosis index (HSI), NAFLD fibrosis score, hemoglobin A1C and other metabolic parameters at two years (Gastrointest Endosc 2020;91[5]:1074-1077). More recently, in the MERIT trial, Dr. Sharaiha, along with lead investigator Barham Abu Dayyeh, MD, from Mayo Clinic in Rochester, Minn.,and others recently documented ESG’s benefits in weight loss, type 2 diabetes, metabolic syndrome, MASLD and hypertension (Lancet 2022;400[10350]:441-451).
Treatment with semaglutide versus placebo also was shown to improve nonalcoholic steatohepatitis (NASH), now called metabolic dysfunction–associated steatohepatitis, but not fibrosis in a phase 2 trial (P<0.0001) (N Engl J Med 2021;384[12]:1113-1124). “Because of this, there’s been a push for giving medications to patients with NASH and obesity,” Dr. Sharaiha said.
Weight Loss Significantly Greater With ESG
For the new study, Dr. Sharaiha and her co-investigators evaluated data from patients prospectively recruited to the Innovative Center for Health and Nutrition (ICHANGE) at Weill Cornell Medicine, a multidisciplinary program for patients with metabolic comorbidities related to obesity. The 86 patients were a mean age of 54 years, nearly two-thirds were female, and the mean body mass index (BMI) was approximately 38 kg/m2 in the ESG group and 36 kg/m2 in the semaglutide group. All the patients had diabetes. Those in the ESG and semaglutide treatment groups were matched by age and sex. A total of 33 underwent ESG and 53 received semaglutide.
| Table 1. Differences in Percent TBWL | |||
| Treatment time point, months | ESG TBWL, % | Semaglutide TBWL, % | P value |
|---|---|---|---|
| 3 | 12.5 | 2.6 | <0.001 |
| 6 | 15.9 | 5.9 | <0.001 |
| 12 | 14.3 | 6.9 | 0.001 |
| 24 | 17.1 | 9.2 | 0.07 |
| ESG, endoscopic sleeve gastroplasty; TBWL, total body weight loss. Based on Digestive Disease Week 2023 (abstract 455). | |||
In a multivariable analysis controlling for age, sex and baseline BMI, TBWL was significantly greater with ESG than with semaglutide at three, six and 12 months (Table 1). In addition, a trend favoring ESG was observed at 24 months, but it was not statistically significant.
“The weight loss for ESG is similar to what we’ve seen with other data, and the weight loss for semaglutide was 9.2%,” Dr. Sharaiha said. However, she noted that this smaller weight loss with semaglutide—somewhat less than is often seen with the drug—could be due to the fact that the dosage was for diabetes management (maximum, 1 mg) and not for the purpose of weight loss (usually a higher dosage).
| Table 2. Change in HSI | |||
| Treatment | HSI baseline | HSI at 6 monthsa | HSI at 12 monthsa |
|---|---|---|---|
| ESG | 48.3 | 44.4 (P=0.06) | 44.4 (P=0.05) |
| Semaglutide | 48.9 | 41.3 (P=0.006) | 33.4 (P=0.001) |
| ESG vs. semaglutide, absolute difference | NA | 4.08 (P=0.1) | 11.0 (P=0.002) |
| a Difference vs. baseline. ESG, endoscopic sleeve gastroplasty; HSI, hepatic steatosis index, NA, not applicable. Based on Digestive Disease Week 2023 (abstract 455). | |||
The patients also had significant improvements in HSI (Table 2) but not in Fibrosis-4 score (which was low at baseline, Dr. Sharaiha noted).
She acknowledged that the study had a small sample size, lack of information on compliance, and used a lower semaglutide dose than that approved for weight loss, but said the results add to the data supporting both therapies as options for patients with obesity and MASLD.
“I think combination therapy is the future,” Dr. Sharaiha said. “Semaglutide and other GLP-1 agonists are a good starting point for these patients, but eventually they will plateau on these or want to go off them. We need something else, and that’s where endoscopic options come in. On the flip side, patients treated with ESG or intragastric balloons may need help maintaining weight loss. Medication initiation here would be key to get better weight loss.”
In the end, she added, “the most important treatment for obesity is to initiate that treatment, whatever the modality.”
Consensus Criteria Needed
Jonathan G. Stine, MD, MSc, the program director of the Penn State Health Fatty Liver Program, in Hershey, Pa., pointed out that the best approach to weight loss for patients with metabolic disorders remains debatable. “This presents patients with many different options to consider and providers to navigate,” he said.
The MERIT trial found ESG plus lifestyle intervention to be superior to lifestyle intervention alone in achieving TBWL. “On the heels of this recent publication, the current study found weight loss was greater with ESG than with semaglutide, although semaglutide was dosed according to best practices for glycemic control and not loss of body weight,” he noted.
“While these initial results are promising and provide the basis for a prospective clinical trial directly comparing the two interventions, they should be interpreted with caution, given several limitations,” he said. They include a lack of standardized criteria for determining which of the two intervention patients who did not achieve weight loss with lifestyle intervention alone subsequently received.
“There are yet to be agreed-upon consensus criteria for determining who should pursue ESG instead of noninvasive management with medications and/or lifestyle intervention alone. What is clear, however, is that ESG is a novel treatment with early data showing it is a safe and efficacious option for patients who need to lose body weight but are unable to do so with traditional lifestyle approaches,” Dr. Stine said. “Determining who will derive the most benefit from ESG as well as reinforcing preliminary long-term outcomes following this procedure remains a key unmet need the GI and hepatology community will need to address.”
—Caroline Helwick
Dr. Sharaiha reported financial relationships with Boston Scientific, Cook Medical and Intuitive Surgical. Dr. Stine reported financial relationships with AstraZeneca, Galectin, Noom, Novo Nordisk and Zydus.
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