TY - JOUR
T1 - Lixisenatide versus insulin glulisine on fasting and postbreakfast systemic hemodynamics in type 2 diabetes mellitus patients
AU - Tonneijck, Lennart
AU - Muskiet, Marcel H.A.
AU - Twisk, Jos W.
AU - Kramer, Mark H.H.
AU - Jan Danser, A. H.
AU - Joles, Jaap A.
AU - Smits, Mark M.
AU - Van Raalte, Daniël H.
N1 - Funding Information:
This was an investigator-initiated study, entirely planned and conducted under the scientific supervision of M. Diamant and, after her passing in 2014, D.H. van Raalte and M.H.H. Kramer. Funding for the study was provided by Sanofi-Aventis. The funder had no role in the study design, the analyses, or interpretation of the data, or drafting the article. The funder had no role in the decision to submit this article for publication. Sanofi-Aventis provided prefilled lixisenatide and insulin glulisine pens for subcutaneous use. The self-monitoring blood glucose devices were provided by Menarini Diagnostics.
Publisher Copyright:
© 2018 American Heart Association, Inc.
PY - 2018
Y1 - 2018
N2 - The prolonged treatment effects of a short-acting GLP-1RA (glucagon-like peptide-1 receptor agonist), such as lixisenatide, on fasting and postprandial systemic hemodynamics in type 2 diabetes mellitus patients are unknown. In this secondary analysis, we included 34 overweight insulin glargine-treated type 2 diabetes mellitus patients (mean±SD age, 62±7 years; HbA 1c , 8.0±0.9%; systolic blood pressure [BP], 133.9±16.1 mm Hg; diastolic BP, 75.4±8.39 mm Hg) that were randomized to once-daily lixisenatide 20 μg or once-daily titrated insulin glulisine for 8 weeks. Systemic hemodynamics (oscillometric device and finger photoplethysmography), arterial stiffness (applanation tonometry), and cardiac sympathovagal balance (heart rate variability) were measured in the fasting state and repetitively (up to minute 175) after a standardized mixed breakfast. Acetaminophen was given orally to estimate gastric emptying rate. Lixisenatide did not affect fasting systemic hemodynamics compared with insulin glulisine from baseline to week 8. Postbreakfast overall, lixisenatide compared with insulin glulisine tended to increase systolic BP by 5.2±2.9 mm Hg (P=0.087) and increased diastolic BP by 5.4±1.4 mm Hg (P<0.001), with respective maximal differences of +10.2±3.7 mm Hg (P=0.007) and +7.2±1.5 mm Hg (P<0.001). Lixisenatide increased systemic vascular resistance (P<0.001) and arterial stiffness (P=0.007). No between-group differences in overall postbreakfast heart rate, cardiac output, or cardiac sympathovagal balance, and circulating catecholamines, angiotensin II, or aldosterone were observed. Both treatments lowered HbA 1c similarly, whereas lixisenatide achieved greater reductions in postbreakfast plasma glucose excursions. Lixisenatide slowed gastric emptying rate, which statistically explained changes in postbreakfast BP. Lixisenatide compared with once-daily titrated insulin glulisine for 8 weeks does not affect fasting but increases postbreakfast BP in insulin glargine-treated type 2 diabetes mellitus patients. This effect could, at least in part, be explained by reduced passage rate of nutrients and water and activation of the gastrovascular reflex.
AB - The prolonged treatment effects of a short-acting GLP-1RA (glucagon-like peptide-1 receptor agonist), such as lixisenatide, on fasting and postprandial systemic hemodynamics in type 2 diabetes mellitus patients are unknown. In this secondary analysis, we included 34 overweight insulin glargine-treated type 2 diabetes mellitus patients (mean±SD age, 62±7 years; HbA 1c , 8.0±0.9%; systolic blood pressure [BP], 133.9±16.1 mm Hg; diastolic BP, 75.4±8.39 mm Hg) that were randomized to once-daily lixisenatide 20 μg or once-daily titrated insulin glulisine for 8 weeks. Systemic hemodynamics (oscillometric device and finger photoplethysmography), arterial stiffness (applanation tonometry), and cardiac sympathovagal balance (heart rate variability) were measured in the fasting state and repetitively (up to minute 175) after a standardized mixed breakfast. Acetaminophen was given orally to estimate gastric emptying rate. Lixisenatide did not affect fasting systemic hemodynamics compared with insulin glulisine from baseline to week 8. Postbreakfast overall, lixisenatide compared with insulin glulisine tended to increase systolic BP by 5.2±2.9 mm Hg (P=0.087) and increased diastolic BP by 5.4±1.4 mm Hg (P<0.001), with respective maximal differences of +10.2±3.7 mm Hg (P=0.007) and +7.2±1.5 mm Hg (P<0.001). Lixisenatide increased systemic vascular resistance (P<0.001) and arterial stiffness (P=0.007). No between-group differences in overall postbreakfast heart rate, cardiac output, or cardiac sympathovagal balance, and circulating catecholamines, angiotensin II, or aldosterone were observed. Both treatments lowered HbA 1c similarly, whereas lixisenatide achieved greater reductions in postbreakfast plasma glucose excursions. Lixisenatide slowed gastric emptying rate, which statistically explained changes in postbreakfast BP. Lixisenatide compared with once-daily titrated insulin glulisine for 8 weeks does not affect fasting but increases postbreakfast BP in insulin glargine-treated type 2 diabetes mellitus patients. This effect could, at least in part, be explained by reduced passage rate of nutrients and water and activation of the gastrovascular reflex.
KW - Blood pressure
KW - Cardiovascular diseases
KW - Diabetes mellitus
KW - Glucagon-like peptide 1
KW - Hemodynamics
UR - https://www.scopus.com/pages/publications/85056533156
U2 - 10.1161/HYPERTENSIONAHA.117.10740
DO - 10.1161/HYPERTENSIONAHA.117.10740
M3 - Article
C2 - 29915021
AN - SCOPUS:85056533156
SN - 0194-911X
VL - 72
SP - 314
EP - 322
JO - Hypertension
JF - Hypertension
IS - 2
ER -