Greater BMI Reduction With Semaglutide Tied to Metabolic Improvements in Adolescents With Severe Obesity

In a retrospective chart review of adolescents with severe obesity treated with semaglutide, greater reductions in body mass index (BMI) were associated with improvements in triglycerides, the triglyceride-to-HDL ratio, and HbA1c. Improvements in triglycerides and markers of insulin resistance were also observed in some patients who did not lose weight, according to data presented at the Endocrine Society (ENDO) Annual Meeting 2026.

The late-breaking poster, presented by Robert Daly, MS4, a medical student at Rutgers Robert Wood Johnson Medical School, examined clinical variability in response to semaglutide among 96 adolescents with severe obesity, defined as a BMI > 30, treated for 6 months to 2 years

“While many patients achieve significant reductions in body weight, a subset demonstrates suboptimal or minimal response,” Daly and colleagues wrote. “The mechanisms underlying this variability are not fully understood and may involve differences in central appetite regulation, pharmacogenomics, insulin resistance, and behavioral factors.”

How Adolescents Were Grouped by BMI Response to Semaglutide

The cohort had a mean age of 16.5 ± 2.6 years and a mean baseline BMI of 40 ± 7.5 kg/m², and 68.8% (66 of 96) were female. Overall, 56 patients (61.5%) were classified by the investigators as having achieved meaningful weight loss.

Daly and colleagues stratified patients into 4 groups based on the effect of semaglutide on BMI:

1. ≥10% BMI reduction. Includes 33 patients (34.4% of total cohort), BMI decreased from 38.9 ‡ 7.1 to 31.4 = 6.5 kg/m?, Mean reduction: 19 = 8.3%, 1 patient (3%) had diabetes.
2. 5-9% BMI reduction. Includes 26 patients (27.1%), including 9 males, BMI decreased from 40.5 ‡ 7.4 to 37.8 = 6.5 kg/m?, Mean reduction: 6.7 = 1.3%, 7 patients (27%) had diabetes
3. Weight gain. Includes 18 patients (18.8%), including 6 males, BMI increased from 40.1 = 8.5 to 42.3 = 9.4 kg/m?, Mean increase: 5.3 ‡ 4.5% 5 patients (28%) had diabetes.
4. No significant BMI change. Includes 19 patients (19.7%), 8 males, BMI changed from 41.3 = 7.9 to 40.4 = 7.8 kg/m?, Mean change: -0.9 = 0.5%; 6 patients (31.5%) had diabetes.

Metabolic Marker Changes Varied by BMI Response Group

According to investigators, several metabolic markers changed significantly (P < .05) in the groups with greater BMI reduction, according to data reported on the poster. In the group with a BMI reduction of ≥ 10%, mean triglycerides decreased from 152 to 105.7 mg/dL, the triglyceride-to-HDL ratio decreased from 3.4 to 2.2, and HbA1c decreased from 6.0% to 5.3%; LDL, ALT, and AST did not change significantly. In the group with a 5% to 9% BMI reduction, triglycerides, the triglyceride-to-HDL ratio, ALT, and AST all decreased significantly, while HbA1c and LDL did not change significantly.

Among the 18 patients who gained weight, mean triglycerides nonetheless decreased from 121.2 to 91.9 mg/dL, and the triglyceride-to-HDL ratio decreased from 2.9 to 2.1, while the other measured markers did not change significantly. In the group with no significant BMI change, none of the measured metabolic markers showed a statistically significant change.