title: Effect of canagliflozin, a sodium glucose co-transporter 2 inhibitor, on C-peptide kinetics.
abstract: Canagliflozin, a sodium glucose co-transporter 2 inhibitor, improves indices of β-cell function estimated based on circulating C-peptide and glucose concentrations (e.g., Homeostasis Model Assessment [HOMA2-%B], meal tolerance test-based indices). However, use of these β-cell function indices assumes C-peptide kinetics are not altered by canagliflozin. This 2-period crossover study assessed the effect of a single canagliflozin 300-mg dose on C-peptide kinetics in 10 healthy participants. Two hours after receiving canagliflozin or placebo, participants received intravenous somatostatin infusion to suppress endogenous C-peptide secretion and 1 hour later received a bolus injection of synthetic human C-peptide 150 µg. Serum C-peptide was measured over 3 hours and urinary glucose and C-peptide excretion were measured. C-peptide kinetic parameters, including total clearance (CLtotal ) and renal clearance (CLrenal ), were calculated. Serum C-peptide profiles were similar following canagliflozin or placebo treatment. C-peptide CLtotal was slightly lower with canagliflozin versus placebo (mean (SD) of 190 (37) vs. 197 (30) mL/min; canagliflozin/placebo ratio [90% CI] = 96.1% [93.0%; 99.3%]). Other kinetic parameters, including CLrenal , were generally similar between treatments. Results indicate canagliflozin 300 mg does not meaningfully alter C-peptide clearance or other kinetic parameters; therefore, C-peptide-based measurements of insulin secretion are appropriate for assessing β-cell function in canagliflozin-treated participants.
authors.affiliation: Janssen Research & Development, LLC, San Diego, CA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Polidori
authors.affiliation: Janssen Research & Development, LLC, Raritan, NJ, USA.
authors.forename: Sue
authors.initials: S
authors.lastname: Sha
authors.affiliation: Profil, Neuss, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Heise
authors.affiliation: Janssen Research & Development, LLC, Raritan, NJ, USA.
authors.forename: Jaya
authors.initials: J
authors.lastname: Natarajan
authors.affiliation: Janssen Research & Development, LLC, Raritan, NJ, USA.
authors.forename: Eunice
authors.initials: E
authors.lastname: Artis
authors.affiliation: Janssen Research & Development, LLC, Raritan, NJ, USA.
authors.forename: Shean-Sheng
authors.initials: SS
authors.lastname: Wang
authors.affiliation: Janssen Research & Development, LLC, Raritan, NJ, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Vaccaro
authors.affiliation: Janssen Research & Development, LLC, Raritan, NJ, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Rothenberg
authors.affiliation: Profil, Neuss, Germany.
authors.forename: Alin
authors.initials: A
authors.lastname: Stirban
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002096:C-Peptide / Q000097:blood* / Q000652:urine*; D000068896:Canagliflozin / Q000008:administration & dosage* / Q000009:adverse effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005858:Germany; D064368:Healthy Volunteers; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D051297:Sodium-Glucose Transporter 2 / Q000378:metabolism; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D055815:Young Adult
chemical_list: D015415:Biomarkers; D002096:C-Peptide; D007004:Hypoglycemic Agents; C089180:SLC5A2 protein, human; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D000068896:Canagliflozin
keywords: C-peptide; canagliflozin; kinetics; sodium glucose co-transporter 2 (SGLT2) inhibitor; β-cell function