Variation in Inflammatory Markers and Glycemic Parameters After 12 Months of Exenatide Plus Metformin Treatment Compared with Metformin Alone: A Randomized Placebo‐Controlled Trial. Issue 8 (6th June 2013)

• Record Type: Journal Article
• Authors: Derosa, Giuseppe; Franzetti, Ivano G.; Querci, Fabrizio; Carbone, Anna; Ciccarelli, Leonardina; Piccinni, Mario N.; Fogari, Elena; Maffioli, Pamela
• Is Part Of: Pharmacotherapy. Volume 33:Issue 8(2013)
• Page Start: 817
• Page End: 826
• Publication Date: 2013-06-06
• Subjects: Chemotherapy -- Periodicals; Pharmacology -- Periodicals; Drug Therapy -- Periodicals; Pharmacology -- Periodicals; 615.1
• DOI: 10.1002/phar.1301
• Languages: English
• ISSNs: 0277-0008

Abstract

<abstract abstract-type="main" id="phar1301-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="phar1301-sec-0001" sec-type="section"> <title>Study Objective</title> <p>To evaluate the effects of exenatide on some inflammatory markers and to quantify the effect of exenatide on β‐cell function.</p> </sec> <sec id="phar1301-sec-0002" sec-type="section"> <title>Design</title> <p>A randomized, double‐blind, placebo‐controlled trial.</p> </sec> <sec id="phar1301-sec-0003" sec-type="section"> <title>Setting</title> <p>Seven hospitals in Italy.</p> </sec> <sec id="phar1301-sec-0004" sec-type="section"> <title>Patients</title> <p>A total of 174 white treatment‐naive adults with type 2 diabetes and a glycated hemoglobin (HbA<sub>1c</sub>) level higher than 7.5%.</p> </sec> <sec id="phar1301-sec-0005" sec-type="section"> <title>Intervention</title> <p>After an open‐label run‐in period of 8 ± 2 months with metformin, patients were randomized to take exenatide (5 μg twice/day for the first 4 weeks, 10 μg twice/day thereafter) or a placebo volume equivalent for 12 months.</p> </sec> <sec id="phar1301-sec-0006" sec-type="section"> <title>Measurements and Main Results</title> <p>Body mass index, HbA<sub>1c</sub>, fasting plasma glucose, postprandial plasma glucose, fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index, homeostasis model assessment β‐cell function index (HOMA‐β), fasting plasma proinsulin (FPPr), proinsulin‐to‐fasting plasma insulin ratio (Pr:FPI ratio), C‐peptide, glucagon, vaspin, chemerin, and resistin were evaluated at baseline, at randomization, and at 3, 6, 9, and 12 months. Patients also underwent a combined euglycemic, hyperinsulinemic, and hyperglycemic clamp with subsequent arginine stimulation to assess insulin sensitivity and insulin secretion. HbA<sub>1c</sub> was significantly improved with exenatide plus metformin compared with placebo plus metformin. Exenatide plus metformin was also significantly more effective than placebo plus metformin in increasing HOMA‐β C‐peptide, and all measures of β‐cell function after the euglycemic hyperinsulinemic and hyperglycemic clamp. We observed that exenatide plus metformin also reduced resistin compared with placebo plus metformin. No variations in vaspin and chemerin were noted in group‐to‐group comparisons. We observed a significant correlation between M value increase, an index of insulin sensitivity, and a decrease in inflammatory parameters in the exenatide plus metformin group.</p> </sec> <sec id="phar1301-sec-0007" sec-type="section"> <title>Conclusions</title> <p>The combination of exenatide plus metformin was more effective than metformin alone in improving glycemic control, β‐cell function, and inflammatory parameters.</p> </sec> </abstract>