SeMaglutide and Albuminuria Reduction Trial in obese individuals without diabetes

Overweight and obese conditions are a global health problem. A strong
interaction exists between obesity and chronic kidney disease (CKD). The
pathophysiological mechanisms underlying this interaction are complex and
involve hemodynamic perturbations leading to increased intra-glomerular
pressure and single nephron hyperfiltration, inflammation, oxidative stress,
and apoptosis. Glucagon Like Peptide 1 Receptor Agonist (GLP1-RA) therapies
have been introduced as antidiabetic drugs. In addition, GLP1-RA therapies
reduce body weight, in patients with and without diabetes, without inducing
hypoglycemia. Moreover, GLP1-RA reduce albuminuria in patients with type 2
diabetes, and liraglutide and semaglutide have been shown to improve various
risk markers of CKD progression in non-diabetic obese individuals. It is
therefore likely that these agents delay progression of kidney function decline
in high risk obese/overweight, non-diabetic individuals.

The main objective of the study is to assess the albuminuria lowering effects
of semaglutide 2.4 mg s.c. once weekly (Semaglutide 3 mg/ml) compared to
placebo in obese/overweight non-diabetic individuals with elevated albuminuria.

A 24-week randomized placebo controlled double-blind two arm parallel clinical
trial with a 4 week wash-out period after 24 weeks double blind treatment to
assess off drug effects.

Eligible participants will be randomly assigned to 24 weeks treatment with
either semaglutide s.c. 2.4 mg once weekly (Semaglutide 3 mg/ml) or placebo.
The starting dose of semaglutide will be 0.24 mg subcutaneous injection with
increasing doses of semaglutide at 4, 8, 12, and 16 weeks to 0.5, 1,0, 1.7 and
2.4 mg.

Patients visit the outpatient clinic on a more regular basis than standard
patient care - i.e. 10 visits to the out-patient clinical department for
clinical assessments during a total study duration of 28 week. A blood sample
is collected for clinical chemistry at each visit. At screening, randomization,
week 20, 22, 24 and 28 three first morning void urine samples will be
collected. At other visits a single first morning void urine is collected. In
46 patients, non-radioactive iohexol clearance will be assessed to determine
GFR. Iohexol clearance measurements will be performed at three visits: at the
start and at the end of the 24-weeks double blind treatment period as well as
at the end of the wash-out period at week 28. Extracellular volume and total
body water will be measured at randomization, week 16, 20 24 and 28 with
bio-impedance spectroscopy. There are no direct benefits for the patients to be
included and participation is on a voluntary basis. Participants can withdraw
from participation at any time without it affecting their standard of medical
care.