title: Effects of the once-weekly glucagon-like peptide-1 receptor agonist dulaglutide on ambulatory blood pressure and heart rate in patients with type 2 diabetes mellitus.
abstract: Glucagon-like peptide-1 receptor agonists, used to treat type 2 diabetes mellitus, are associated with small reductions in systolic blood pressure (SBP) and increases in heart rate. However, findings based on clinic measurements do not adequately assess a drug's 24-hour pharmacodynamic profile. The effects of dulaglutide, a once-weekly glucagon-like peptide-1 receptor agonist, on BP and heart rate were investigated using ambulatory BP monitoring. Patients (n=755; 56±10 years; 81% white; 48% women), with type 2 diabetes mellitus, taking ≥1 oral antihyperglycemic medication, with a clinic BP between 90/60 and 140/90 mm Hg were randomized to dulaglutide (1.5 or 0.75 mg) or placebo subcutaneously for 26 weeks. Ambulatory BP monitoring was performed at baseline and at 4, 16, and 26 weeks. The primary end point was change from baseline to week 16 in mean 24-hour SBP, a tree gatekeeping strategy compared the effects of dulaglutide to placebo. Both doses of dulaglutide were noninferior to placebo for changes in 24-hour SBP and diastolic blood pressure, and dulaglutide 1.5 mg significantly reduced SBP (least squares mean difference [95% confidence interval]), -2.8 mm Hg [-4.6, -1.0]; P≤0.001). Dulaglutide 0.75 mg was noninferior to placebo (1.6 bpm; [0.3, 2.9]; P≤0.02) for 24-hour heart rate (least squares mean difference [95% confidence interval]), but dulaglutide 1.5 mg was not (2.8 bpm [1.5, 4.2]). Dulaglutide 1.5 mg was associated with a reduction in 24-hour SBP and an increase in 24-hour heart rate. The mechanisms responsible for the observed effects remain to be clarified.
authors: From the Tulane University School of Medicine, New Orleans, LA (K.C.F.); Calhoun Cardiology Center, University of Connecticut School of Medicine, Farmington (W.B.W.); University of Alabama at Birmingham (D.A.C.); McMaster University, Hamilton, Ontario, Canada (E.M.L.); Sager Consulting, San Francisco, CA (P.T.S.); B2S Consulting, Carmel, IN (R.B.); and Lilly Diabetes, Eli Lilly and Company, Indianapolis, IN (H.H.J., R.J.T., K.E.R., M.J.G.). kferdina@tulane.edu.
authors: Keith C
authors: KC
authors: Ferdinand
authors: From the Tulane University School of Medicine, New Orleans, LA (K.C.F.); Calhoun Cardiology Center, University of Connecticut School of Medicine, Farmington (W.B.W.); University of Alabama at Birmingham (D.A.C.); McMaster University, Hamilton, Ontario, Canada (E.M.L.); Sager Consulting, San Francisco, CA (P.T.S.); B2S Consulting, Carmel, IN (R.B.); and Lilly Diabetes, Eli Lilly and Company, Indianapolis, IN (H.H.J., R.J.T., K.E.R., M.J.G.).
authors: William B
authors: WB
authors: White
authors: From the Tulane University School of Medicine, New Orleans, LA (K.C.F.); Calhoun Cardiology Center, University of Connecticut School of Medicine, Farmington (W.B.W.); University of Alabama at Birmingham (D.A.C.); McMaster University, Hamilton, Ontario, Canada (E.M.L.); Sager Consulting, San Francisco, CA (P.T.S.); B2S Consulting, Carmel, IN (R.B.); and Lilly Diabetes, Eli Lilly and Company, Indianapolis, IN (H.H.J., R.J.T., K.E.R., M.J.G.).
authors: David A
authors: DA
authors: Calhoun
authors: From the Tulane University School of Medicine, New Orleans, LA (K.C.F.); Calhoun Cardiology Center, University of Connecticut School of Medicine, Farmington (W.B.W.); University of Alabama at Birmingham (D.A.C.); McMaster University, Hamilton, Ontario, Canada (E.M.L.); Sager Consulting, San Francisco, CA (P.T.S.); B2S Consulting, Carmel, IN (R.B.); and Lilly Diabetes, Eli Lilly and Company, Indianapolis, IN (H.H.J., R.J.T., K.E.R., M.J.G.).
authors: Eva M
authors: EM
authors: Lonn
authors: From the Tulane University School of Medicine, New Orleans, LA (K.C.F.); Calhoun Cardiology Center, University of Connecticut School of Medicine, Farmington (W.B.W.); University of Alabama at Birmingham (D.A.C.); McMaster University, Hamilton, Ontario, Canada (E.M.L.); Sager Consulting, San Francisco, CA (P.T.S.); B2S Consulting, Carmel, IN (R.B.); and Lilly Diabetes, Eli Lilly and Company, Indianapolis, IN (H.H.J., R.J.T., K.E.R., M.J.G.).
authors: Philip T
authors: PT
authors: Sager
authors: From the Tulane University School of Medicine, New Orleans, LA (K.C.F.); Calhoun Cardiology Center, University of Connecticut School of Medicine, Farmington (W.B.W.); University of Alabama at Birmingham (D.A.C.); McMaster University, Hamilton, Ontario, Canada (E.M.L.); Sager Consulting, San Francisco, CA (P.T.S.); B2S Consulting, Carmel, IN (R.B.); and Lilly Diabetes, Eli Lilly and Company, Indianapolis, IN (H.H.J., R.J.T., K.E.R., M.J.G.).
authors: Rocco
authors: R
authors: Brunelle
authors: From the Tulane University School of Medicine, New Orleans, LA (K.C.F.); Calhoun Cardiology Center, University of Connecticut School of Medicine, Farmington (W.B.W.); University of Alabama at Birmingham (D.A.C.); McMaster University, Hamilton, Ontario, Canada (E.M.L.); Sager Consulting, San Francisco, CA (P.T.S.); B2S Consulting, Carmel, IN (R.B.); and Lilly Diabetes, Eli Lilly and Company, Indianapolis, IN (H.H.J., R.J.T., K.E.R., M.J.G.).
authors: Honghua H
authors: HH
authors: Jiang
authors: From the Tulane University School of Medicine, New Orleans, LA (K.C.F.); Calhoun Cardiology Center, University of Connecticut School of Medicine, Farmington (W.B.W.); University of Alabama at Birmingham (D.A.C.); McMaster University, Hamilton, Ontario, Canada (E.M.L.); Sager Consulting, San Francisco, CA (P.T.S.); B2S Consulting, Carmel, IN (R.B.); and Lilly Diabetes, Eli Lilly and Company, Indianapolis, IN (H.H.J., R.J.T., K.E.R., M.J.G.).
authors: Rebecca J
authors: RJ
authors: Threlkeld
authors: From the Tulane University School of Medicine, New Orleans, LA (K.C.F.); Calhoun Cardiology Center, University of Connecticut School of Medicine, Farmington (W.B.W.); University of Alabama at Birmingham (D.A.C.); McMaster University, Hamilton, Ontario, Canada (E.M.L.); Sager Consulting, San Francisco, CA (P.T.S.); B2S Consulting, Carmel, IN (R.B.); and Lilly Diabetes, Eli Lilly and Company, Indianapolis, IN (H.H.J., R.J.T., K.E.R., M.J.G.).
authors: Kenneth E
authors: KE
authors: Robertson
authors: From the Tulane University School of Medicine, New Orleans, LA (K.C.F.); Calhoun Cardiology Center, University of Connecticut School of Medicine, Farmington (W.B.W.); University of Alabama at Birmingham (D.A.C.); McMaster University, Hamilton, Ontario, Canada (E.M.L.); Sager Consulting, San Francisco, CA (P.T.S.); B2S Consulting, Carmel, IN (R.B.); and Lilly Diabetes, Eli Lilly and Company, Indianapolis, IN (H.H.J., R.J.T., K.E.R., M.J.G.).
authors: Mary Jane
authors: MJ
authors: Geiger
mesh_terms: D000368:Aged; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D018660:Blood Pressure Monitoring, Ambulatory; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D003967:Diarrhea / Q000139:chemically induced; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D000067757:Glucagon-Like Peptide-1 Receptor; D004763:Glucagon-Like Peptides / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006442:Glycated Hemoglobin / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use; D007141:Immunoglobulin Fc Fragments / Q000009:adverse effects / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D018027:Receptors, Glucagon / Q000819:agonists*; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced
chemical_list: D000067757:Glucagon-Like Peptide-1 Receptor; D004763:Glucagon-Like Peptides; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007141:Immunoglobulin Fc Fragments; D018027:Receptors, Glucagon; D011993:Recombinant Fusion Proteins; C000593833:GLP1R protein, human; C555680:dulaglutide
keywords: blood pressure; blood pressure monitoring, ambulatory; dulaglutide; glucagon-like peptide-1; heart rate; hypertension; type 2 diabetes mellitus