Digestive Diseases

June 26, 2024

Semaglutide is a Food and Drug Administration-approved anti-obesity medication used for weight management in patients with obesity and type 2 diabetes mellitus (T2DM). In recent randomized clinical trials, semaglutide has achieved significant total body weight-loss percentage (TBWL%) in patients without T2DM. However, researchers have observed that this medication produces much less impressive weight-loss outcomes in patients with T2DM. Although there are multiple hypotheses explaining this discrepancy, little is known about the underlying mechanisms that influence these outcomes.

The individualized metabolic surgery (IMS) score is one of the most widely used, validated scoring systems for predicting diabetes remission in patients after bariatric surgery. It includes four parameters: glycemic control (hemoglobin A1C less than 7%), insulin use, number of T2DM medications and duration of T2DM.

Because the components of the IMS score can be obtained for all patients with T2DM, the score also can be used to classify patients with different severity levels of T2DM. In a retrospective multicenter cohort study, a team of Mayo Clinic researchers sought to assess associations between IMS score categories and weight-loss outcomes among patients with T2DM who were treated with semaglutide. Study results were published in eClinicalMedicine in 2024, with Andres J. Acosta, M.D., Ph.D., serving as the corresponding author. Dr. Acosta is a gastroenterologist, obesity researcher and director of the Precision Medicine for Obesity Laboratory at Mayo Clinic in Rochester, Minnesota.

"This study is especially relevant today due to the increasing prevalence of obesity and type 2 diabetes worldwide," explains Dr. Acosta. "These conditions are major health concerns that lead to significant medical complications and societal costs."

Study methods

The researchers analyzed electronic medical records from 297 Mayo Clinic patients (42% female, mean age 62 ± 12 years) who met the following criteria: diagnosed with T2DM, a body mass index of 27 kg/m² or more, treated with weekly subcutaneous semaglutide injections of 1 mg or more between January 2020 and December 2022 for T2DM or obesity. Patients were excluded if they had a history of bariatric surgery or were taking other anti-obesity medications.

Dr. Acosta and co-authors note that this study is the first multicenter real-world cohort study assessing weight loss, metabolic and cardiovascular disease risk outcomes associated with a range of semaglutide subcutaneous doses in patients with obesity and a follow-up period of up to 12 months.

The researchers documented patient weights and IMS scores at baseline, and they recorded weight changes at three, six, nine and 12 months after the weekly injections began. Patient IMS scores were categorized as mild (0 to 24.9 points), moderate (25 to 94.9 points) and severe (95 to 180 points). The researchers analyzed IMS score quartiles and a combination of mild-moderate versus severe categories. They also performed mixed linear regression models, including age, sex and baseline weight to assess associations between IMS score categories and TBWL%.

Results

• At 12 months, the researchers observed a stepwise decrease in weight-loss outcomes when comparing patients by IMS quartiles: 8.8 ± 0.8% versus 6.9 ± 0.8% versus 5.7 ± 0.9% versus 5.0 ± 0.8%.
• In the mixed linear model, patients in the mild-moderate IMS score category achieved weight-loss outcomes that were superior to outcomes achieved by patients in the severe category at 12 months.
• There was no significant difference in glycemic improvement regardless of IMS score severity category at baseline.

"The key finding from the study — that the effectiveness of semaglutide in promoting weight loss varies significantly with a patient's level of diabetes severity — provides valuable insights for clinical practice," says Dr. Acosta. "Our data suggest that patients with less severe diabetes may experience more substantial weight-loss benefits from semaglutide."

Overall, Dr. Acosta explains that these results highlight the need for personalized treatment approaches to improve health outcomes.

"This information can help healthcare providers better tailor weight management strategies and set realistic expectations for patients with different severities of diabetes," says Dr. Acosta. "Additionally, understanding these dynamics can assist in optimizing treatment plans, improving patient adherence and ultimately enhancing the overall quality of life for those affected."

Next steps

Dr. Acosta notes that further research is needed to explore the underlying mechanisms that cause variations in weight-loss outcomes with semaglutide among patients with different diabetes severities.

"Studies that focus on a broader range of biomarkers and long-term outcomes would be beneficial," says Dr. Acosta. "Additionally, expanding research to include diverse patient populations could ensure that the findings are generalizable across different demographic groups. Implementing randomized controlled trials to validate the predictive value of the IMS score in other anti-obesity medications could also provide deeper insights.

"We are actively involved in several research initiatives focused on improving the effectiveness of treatments for obesity and diabetes," adds Dr. Acosta. "Specifically, we are collaborating with other academic centers to better understand the predictors of clinical response to semaglutide. This collaboration aims to refine how we predict and measure the effectiveness of semaglutide in different patient populations, enhancing personalized treatment approaches."

For more information

Ghusn W, et al. Weight loss outcomes with semaglutide based on diabetes severity using the individualized metabolic surgery score. eClinicalMedicine. 2024;72:102625.

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