title: Effects of a long-acting GLP-1 mimetic (PF-04603629) on pulse rate and diastolic blood pressure in patients with type 2 diabetes mellitus.
abstract: PF-04603629, an exendin-transferrin fusion protein, is a long-acting glucagon-like peptide-1 (GLP-1) mimetic. This randomized, double-blind study characterized the safety and pharmacodynamics of a single dose of PF-04603629 (n = 57; 1-70 mg) or placebo (n = 14) in subjects with type 2 diabetes mellitus (T2DM). There were dose-dependent decreases from baseline in day 6 glucose area under the curve following a mixed meal test (-27 ± 12% with 70 mg). Most treatment-related adverse events were gastrointestinal, with nausea and vomiting most frequent at 70 mg. Pulse rate (PR) and diastolic blood pressure (DBP) increased dose dependently within the normal range. At 24 h postdose mean PR increased 23 ± 9 bpm and mean DBP increased 10 ± 5 mmHg with 70 mg. In conclusion, PF-04603629 exhibited efficacy and tolerability consistent with its mechanism of action; however, PR and DBP increased. Similar effects have been reported occasionally with other GLP-1 mimetics. These data underscore the importance of careful assessments of haemodynamic effects in GLP-1 analogues.
authors.affiliation: Cardiovascular, Metabolic, and Endocrine Diseases Research Unit, Pfizer Pharmatherapeutics Research and Development, Groton, CT, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Gustavson
authors.forename: D
authors.initials: D
authors.lastname: Chen
authors.forename: V
authors.initials: V
authors.lastname: Somayaji
authors.forename: K
authors.initials: K
authors.lastname: Hudson
authors.forename: D J
authors.initials: DJ
authors.lastname: Baltrukonis
authors.forename: J
authors.initials: J
authors.lastname: Singh
authors.forename: T L
authors.initials: TL
authors.lastname: Boyden
authors.forename: R A
authors.initials: RA
authors.lastname: Calle
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects*; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology* / Q000627:therapeutic use; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000494:pharmacology* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D007004:Hypoglycemic Agents; C569029:PF 04603629; D011993:Recombinant Fusion Proteins; D052216:Glucagon-Like Peptide 1