Long-Term Effects of Semaglutide on Body Composition and Performance in Running

Healthy experienced triathletes or distance runners will complete a 12-week intervention with either weekly injections of semaglutide (titrated from 0.25 and up to 1.0 mg) or placebo. Furthermore, participants will complete a follow-up period consisting of 4 weeks without treatment. Before and after the intervention period as well as the follow-up period, participants will complete 2 experimental days (6 experimental days in total). On experimental days, change in body composition, with a particular focus on muscle mass, will be assessed using DXA scans and ultrasound imaging of v. lateralis. In addition, specific performance tests (200-m, 3-km, 10-km) and running economy, as well as hormonal markers in serum and urine will be measured.

• Semaglutide (SEMA) (Drug): The semaglutide group will receive subcutaneous injections with semaglutide, titrated from 0.25 mg up to 1.0 mg once weekly in accordance with standard treatment guidelines (dose increasing every 4 week). After the 12-week intervention period, participants will complete a 4 week follow-up period without treatment.
• Placebo (Drug): The placebo group will receive subcutaneous injections with placebo once weekly. After the 12-week intervention period, participants will complete a 4 week follow-up period without treatment.

Primary outcomes

• Change in total lean mass measured by dual-energy X-ray absorptiometry (DXA) [Baseline (week 0), immediately after the 12-week intervention period (week 12), and immediately after the 4-week follow-up period without treatment (week 16).]: Total lean mass will be assessed using dual-energy X-ray absorptiometry (DXA). The change in total lean mass from baseline to the end of the 4-week intervention period will be calculated (unit of measure: kilograms (kg)).

Secondary outcomes

• Change in muscle thickness measured by ultrasonography [Baseline (week 0), immediately after the 12-week intervention period (week 12), and immediately after the 4-week follow-up period without treatment (week 16).]: Muscle thickness will be assessed by ultrasonography at predefined anatomical sites. The change in muscle thickness from baseline to the end of the 4-week intervention period will be calculated (unit of measure: millimeters (mm)).
• Change in running performance [Baseline (week 0), immediately after the 12-week intervention period (week 12), and immediately after the 4-week follow-up period without treatment (week 16).]: Running performance will be assessed using 200-m, 3-km and 10-km running performance as well as running economy and VO2max during an incremental test on treadmill.
• Change in maximal voluntary isometric quadriceps contraction torque [Baseline (week 0), immediately after the 12-week intervention period (week 12), and immediately after the 4-week follow-up period without treatment (week 16).]: Maximal voluntary isometric contraction torque of the quadriceps muscles will be assessed using an isometric strength test. The change in maximal isometric contraction torque from baseline to the end of the 4-week intervention period will be calculated (unit of measure: newton-meters (N*m)).
• Change in one-repetition maximum (1RM) leg press strength [Baseline (week 0), immediately after the 12-week intervention period (week 12), and immediately after the 4-week follow-up period without treatment (week 16).]: Lower-body muscle strength will be assessed using a one-repetition maximum (1RM) leg press test. The change in 1RM leg press strength from baseline to the end of the 4-week intervention period will be calculated (unit of measure: kilograms (kg)).

Other outcomes

• Changes in serum and urinary steroidal and endocrine biomarkers [Baseline (week 0), immediately after the 12-week intervention period (week 12), and immediately after the 4-week follow-up period without treatment (week 16).]: Serum and urine concentrations of prespecified steroidal and endocrine biomarkers will be measured. Changes in biomarker concentrations from baseline will be assessed following the 12-week intervention and following the 4-week treatment-free follow-up period. Biomarkers will be analyzed individually and reported using their respective units of measurement.

Sex: All, ages: 18 Years to 45 Years, accepts healthy volunteers

Inclusion Criteria:

* Healthy experienced triathletes or distance runners (training history +5 years and weekly training volume >10 h/week)
* Aged 18 to 45 years
* Body mass index (BMI) between 21.0-26.0 kg/m2

Exclusion Criteria:

* Chronic use of medication (except for occasional use of analgesics or antihistamines)
* Chronic disease (e.g. diabetes, disordered eating behavior (EDE-Q >2.5 for females and 1.7 for males))
* Abnormal kidney function, or ECG abnormalities.

For female participants, additional exclusion criteria are

* Pregnancy
* Current or recent use of any hormonal contraceptives the last 6 months (including oral contraceptives, hormonal implants, injectable contraceptives, and hormone-releasing intrauterine devices)
* Irregular menstrual cycles (cycle length outside the 21-35-day range) and anovulatory cycles