Real-World Evidence of the Effect of Adjunctive Semaglutide on Weight Change, Glycemic Control, and Metabolic Dysfunction-Associated Steatotic Liver Disease in People with Type 1 Diabetes.

Abstract

Introduction: Obesity is increasingly prevalent in type 1 diabetes (T1D), contributing to insulin resistance and metabolic dysfunction-associated steatotic liver disease (MASLD). While semaglutide has demonstrated weight loss, improved glycemic control, and cardiovascular benefits in type 2 diabetes, its use in T1D remains unapproved. Aims and Methods: This real-world study evaluates the effects of once-weekly semaglutide in overweight/obese adults with T1D after 12 months of follow-up. Inclusion criteria were stable glycemic control (ΔHbA1c < 0.3%), stable body weight (Δweight < 3%), and consistent total daily insulin requirement (TDI, ΔTDI < 5%) over the preceding year. Changes in weight, total daily insulin dose (TDI), glycated hemoglobin A1c (HbA1c), and metabolic markers, including controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), were assessed at baseline and 12 months. Results: Among 42 subjects (53% male, age 46 ± 12 years, diabetes duration 28 ± 12 years, HbA1c 7.4 ± 0.8%, body mass index 32.2 ± 4.3 kg/m²), 76.2% had obesity. Eight subjects discontinued treatment, mainly due to gastrointestinal intolerance. Mean relative weight loss was 13.3 ± 11.3% (P < 0.001), with 76.4% attaining ≥5% weight loss and 61.7% attaining ≥10%. Obesity prevalence decreased to 29.4% (P < 0.001). HbA1c decreased by 0.4 ± 0.6% (P < 0.001), with 42% achieving a reduction of ≥0.5%. No significant changes in continuous glucose monitoring-derived parameters were observed in those with available data (n = 28). TDI reduced by 13.6 ± 16.0% (P < 0.001), whereas TDI/kg of body weight remained stable. In 23 subjects with serial hepatic imaging, MASLD prevalence reduced from 82.6% to 30.4% (P < 0.001), CAP decreased by 45 ± 33 decibels/m, and significant fibrosis (based on LSM >8 kPa) declined from 20.6% to 4.5% (P < 0.001). Conclusion: Semaglutide in T1D was safe and well-tolerated and led to significant weight loss, improved glycemic control, and amelioration of MASLD.