Semaglutide weight loss results linked to diabetes severity

In a recent study published in eClinicalMedicine, researchers investigate the weight loss outcomes of semaglutide treatment in obese patients with type 2 diabetes (T2D) based on their individualized metabolic surgery (IMS) score.

Study: Weight loss outcomes with semaglutide based on diabetes severity using the individualized metabolic surgery score. Image Credit: Proxima Studio / Shutterstock.com

Factors influencing the effectiveness of semiglutide

Obesity, which affects nearly two billion people globally, is closely associated with T2D and other serious comorbidities such as cardiovascular diseases.

Despite various interventions like lifestyle changes, medications, and bariatric surgery, managing weight loss remains challenging. Among the different anti-obesity medications approved by the United States Food and Drug Administration (FDA), semaglutide has been shown to support significant weight loss in patients without T2D; however, its effectiveness is reduced in those with the condition.

Although previous studies indicate that certain factors, like insulin use, may influence weight loss outcomes, limited data exist on other parameters that may affect the efficacy of semiglutide treatment. The IMS score, which assesses T2D severity using parameters like glycemic control and insulin use, has been validated for predicting T2D remission post-bariatric surgery.

About the study

Researchers theorized that patients with severe T2D, as indicated by higher IMS scores, would experience less weight loss with semaglutide treatment. Thus, the aim of the current study was to evaluate weight loss outcomes based on IMS scores in patients with T2D.

Individuals with a body mass index (BMI) of at least 27 kg/m² who were prescribed at least one milligram (mg) semaglutide, had undergone bariatric surgery, and did not use other medications for weight loss were eligible for the current study.

Baseline clinical and demographic data, including IMS parameters of glycemic control, insulin use, T2D medications, and T2D duration, were collected from electronic medical records. Body weights were recorded at baseline, as well as after three, six, nine, and 12 months to calculate the total body weight loss percentage (TBWL%).

The IMS score, which reflects T2D severity, was determined using an online calculator. The primary endpoint was weight loss at 12 months, calculated from quartile values of IMS scores.

Statistical analysis included mixed linear models with TBWL% as the dependent variable and was adjusted for covariates such as sex, age, baseline weight, and comorbid conditions. Secondary endpoints assessed weight loss by IMS severity categories and changes in levels of fasting glucose and hemoglobin A1c (HbA1c) levels.

Study findings

Of the 1,188 patients initially considered for the study, 297 patients were ultimately included in the analysis. About 5%, 33%, and 63% of the study cohort had mild, moderate, and severe IMS scores, respectively.

At 12 months, weight loss outcomes decreased with increasing IMS severity, with the least square mean TBWL% of 8.8%, 6.9%, 5.7%, and 5% for individuals with mild, moderate, severe, and most severe IMS scores, respectively. A significant difference in weight loss was observed between the mild and most severe groups.

When comparing combined mild-moderate to severe groups, the mild-moderate group had significantly greater weight loss of 8.3% as compared to the severe group at 5.5%. Independent IMS parameters influencing weight loss included insulin use, HbA1c levels, number of T2D medications, and T2D duration.

Patients on insulin lost 5.3% of body weight, whereas those not on insulin lost 7.7%. Patients with HbA1c levels of less than 7% lost 9.4% body weight as compared to 5.8% in those with HbA1c levels exceeding 7%.

Patients prescribed one T2D medication lost 9.7% weight, which was significantly more than those prescribed four or more medications at 2.6%. Patients with a T2D duration of five years or less lost 9% body weight, which was significantly more than those living with T2D for 10-15 years at 5%. No significant differences in glycemic improvements were observed between IMS severity groups.

Conclusions

The current study is the first to evaluate the weight loss outcomes of semaglutide treatment using an innovative scoring system for diabetes severity. To this end, higher T2D severity, which was represented by IMS scores, correlated with lower weight loss outcomes; however, changes in fasting blood glucose and HbA1c were consistent across severities.

Notable strengths of the current study include its large and diverse study cohort, as well as the utilization of a novel scoring system. Some limitations include retrospective data collection, predominance of White and male participants, reduced sample size, and missing weight data.

Future studies are needed to apply the IMS model to clinical trials to validate its predictive capability for weight loss outcomes with semaglutide and other glucagon-like peptide-1 (GLP-1) receptor agonists. Mechanistic studies are also needed better to understand the impact of T2D on weight loss.

Despite lower weight loss in severe T2D, the cardiovascular and comorbidity benefits associated with semaglutide treatment remain significant, thus emphasizing its importance in managing T2D and obesity.