Effect of Semaglutide on Body Weight in Adults with Type 1 Diabetes and Obesity: A Multicentre Randomized Double‑Blind Placebo‑Controlled Trial

The primary objective is to determine the effect of semaglutide on body weight in adults with type 1 diabetes and obesity, addressing the clinical need for weight reduction in this high‑risk population. Secondary objectives include:

• Evaluation of glycemic control (HbA1c, fasting glucose, C‑peptide, continuous glucose monitoring data)
• Assessment of insulin dose requirements
• Measurement of cardiovascular and metabolic biomarkers (lipids, liver function, inflammatory markers)
• Collection of patient‑reported outcomes (diabetes distress, treatment satisfaction)
• Monitoring of safety endpoints such as hypoglycemia and diabetic ketoacidosis
• In a subgroup of 40 participants, additional endpoints comprise insulin sensitivity (hyperinsulinemic euglycemic clamp), changes in body composition and bone density (DXA), and transcriptomic alterations in muscle and adipose tissue obtained through omics analyses

The trial enrolled adult individuals (≥18 years) of both sexes who had a documented history of Type 1 Diabetes for ≥3 years and met obesity criteria (BMI ≥30 kg/m² or BMI ≥27 kg/m² with a concurrent obesity‑related diagnosis such as hypertension, dyslipidemia, or cardiovascular disease). Participants were required to be otherwise generally healthy aside from the specified metabolic conditions. Selection was based on the defined inclusion criteria; no additional lifestyle requirements (e.g., specific diet or activity level) were stipulated. The sponsor did not provide information on the total number of participants enrolled.

The OBES1TY trial is a multicentre, phase 5, randomised, double‑blind, placebo‑controlled study evaluating the effect of semaglutide on body weight in adults with Type 1 Diabetes and obesity. Participants are screened for eligibility, including a minimum diabetes duration of three years, BMI ≥ 30 kg/m² (or ≥ 27 kg/m² with an obesity‑related comorbidity), and age ≥ 18 years. After successful screening, eligible individuals are randomised 1:1 to receive subcutaneous injections of either semaglutide 2.4 mg or matching placebo 0.34 mg once weekly. Follow‑up visits occur at regular intervals to assess primary and secondary endpoints, collect safety data, and monitor adherence; a final end‑of‑study visit concludes the assessment period. Participant involvement spans from the initial screening visit through the end‑of‑study visit, covering the entire trial timeframe scheduled from October 2025 to June 2028.

The investigational product is semaglutide, administered as a subcutaneous injection at a dose of 2.4 mg per administration. The formulation is provided in a sterile injectable form suitable for subcutaneous delivery. The assigned dose is delivered according to the trial’s dosing schedule, which is defined in the protocol and monitored for adherence.

The comparator is a placebo preparation, also delivered by subcutaneous injection at a dose of 0.34 mg per administration. The placebo is formulated to match the appearance of the active product and is administered using the same injection technique and schedule as the investigational arm.

All study participants receive their assigned injection at the same frequency defined by the protocol, and dosing occurs under blinded conditions. Compliance is assessed through documented injection logs, returned study drug vials, and periodic verification by study personnel. Any deviations from the prescribed dosing schedule are recorded and reported according to the trial’s safety monitoring procedures.

The primary efficacy assessment will be based on the change in body weight / BMI from baseline to the end of treatment. Body weight will be measured using calibrated scales, and height will be recorded to calculate BMI at each study visit.

Secondary efficacy parameters include systolic and diastolic blood pressure, resting heart rate, waist circumference, and hip‑waist ratio, all obtained with standard clinical instruments. Laboratory analyses will be performed on fasting blood samples for hematology (hemoglobin, leukocytes, thrombocytes), glycemic control (HbA1c, fasting plasma‑glucose, fasting C‑peptide, ketones), lipid profile (total, HDL, non‑HDL, LDL, VLDL cholesterol, triglycerides), renal function (sodium, potassium, creatinine/eGFR, albumin), hepatic and gastrointestinal markers (alanine and aspartate transaminase, fibrosis‑4 score, amylase, lipase), and high‑sensitivity C‑reactive protein. Continuous glucose monitoring data will be collected to evaluate time in range, time above range, time below range, time in tight range, and coefficient of variation. Total daily insulin dose will be self‑reported by participants. Insulin sensitivity will be quantified in a predefined subgroup using the hyperinsulinemic euglycemic clamp. Body composition, including fat percentage, lean mass, and bone mineral content, will be assessed in the same subgroup by DXA scans. Additional exploratory measures comprise omics and metabolomic profiling of plasma, transcriptomic analysis of muscle and adipose tissue biopsies, standard 12‑lead electrocardiograms, and patient‑reported outcomes obtained through questionnaires on dietary patterns, diabetes treatment satisfaction, and diabetes‑related distress.