title: Pharmacokinetics and Tolerability of a Single Dose of Semaglutide, a Human Glucagon-Like Peptide-1 Analog, in Subjects With and Without Renal Impairment.
abstract: The pharmacokinetics and tolerability of semaglutide, a once-weekly human glucagon-like peptide-1 analog in development for the treatment of type 2 diabetes mellitus, were investigated in subjects with/without renal impairment (RI).
  
  
  
  Fifty-six subjects, categorized into renal function groups [normal, mild, moderate, severe, and end-stage renal disease (ESRD)], received a single subcutaneous dose of semaglutide 0.5 mg. Semaglutide plasma concentrations were assessed ≤480 h post-dose; the primary endpoint was the area under the plasma concentration-time curve from time zero to infinity.
  
  
  
  Semaglutide exposure in subjects with mild/moderate RI and ESRD was similar to that in subjects with normal renal function. In subjects with severe RI, the mean exposure of semaglutide was 22% higher than in subjects with normal renal function, and the 95% confidence interval (1.02-1.47) for the ratio exceeded the pre-specified limits (0.70-1.43). When adjusted for differences in sex, age, and body weight between the groups, all comparisons were within the pre-specified clinically relevant limits. Across RI groups there was no relationship between creatinine clearance (CLCR) and semaglutide exposure, or between CLCRand semaglutide maximum plasma drug concentration (Cmax). Hemodialysis did not appear to affect the pharmacokinetics of semaglutide. No appreciable changes in safety parameters or vital signs and no serious adverse events were noted. One subject with severe RI reported two major hypoglycemic events.
  
  
  
  When adjusted for differences in sex, age, and body weight, semaglutide exposure was similar between subjects with RI and subjects with normal renal function. Semaglutide (0.5 mg) was well-tolerated. Dose adjustment may not be warranted for subjects with RI. CLINICALTRIALS.
  
  
  
  NCT00833716.
authors.affiliation: Orlando Clinical Research Center, 5055 South Orange Avenue, Orlando, FL, 32809, USA. tmarbury@ocrc.net.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Marbury
authors.affiliation: Novo Nordisk A/S, Søborg, Denmark.
authors.forename: Anne
authors.initials: A
authors.lastname: Flint
authors.affiliation: Novo Nordisk A/S, Søborg, Denmark.
authors.forename: Jacob B
authors.initials: JB
authors.lastname: Jacobsen
authors.affiliation: Novo Nordisk A/S, Søborg, Denmark.
authors.forename: Julie
authors.initials: J
authors.lastname: Derving Karsbøl
authors.affiliation: Clinical Pharmacology of Miami, Inc., Miami, FL, USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Lasseter
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives*; D004763:Glucagon-Like Peptides / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D051437:Renal Insufficiency / Q000097:blood / Q000150:complications*; D055815:Young Adult; D000099194:Semaglutide
chemical_list: D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D007004:Hypoglycemic Agents; D000099194:Semaglutide