Diastolic Cardiac Function Improvement by Liraglutide Is Mainly Body Weight Reduction Dependent but Independently Contributes to B-Type Natriuretic Peptide Reduction in Patients with Type 2 Diabetes with Preserved Ejection Fraction

<jats:p>Objectives. A single-arm prospective study was conducted among Japanese patients with type 2 diabetes having preserved ejection fraction. The aim was to investigate (1) whether liraglutide therapy could improve B-type natriuretic peptide (BNP) levels and diastolic cardiac function assessed by the <jats:inline-formula> <math xmlns="http://www.w3.org/1998/Math/MathML" id="M1"> <mi>E</mi> </math> </jats:inline-formula>-wave to <jats:inline-formula> <math xmlns="http://www.w3.org/1998/Math/MathML" id="M2"> <msup> <mrow> <mi>E</mi> </mrow> <mrow> <mo>′</mo> </mrow> </msup> </math> </jats:inline-formula> ratio (<jats:inline-formula> <math xmlns="http://www.w3.org/1998/Math/MathML" id="M3"> <mi>E</mi> <mo>/</mo> <msup> <mrow> <mi>E</mi> </mrow> <mrow> <mo>′</mo> </mrow> </msup> </math> </jats:inline-formula>) using transthoracic echocardiography (TTE), and (2) whether <jats:inline-formula> <math xmlns="http://www.w3.org/1998/Math/MathML" id="M4"> <mi>E</mi> <mo>/</mo> <msup> <mrow> <mi>E</mi> </mrow> <mrow> <mo>′</mo> </mrow> </msup> </math> </jats:inline-formula> contributed to BNP improvement independent of bodyweight reduction (UMIN000005565). Methods. Patients with type 2 diabetes and <jats:inline-formula> <math xmlns="http://www.w3.org/1998/Math/MathML" id="M5"> <mtext>left</mtext> <mtext> </mtext> <mtext>ventricular</mtext> <mtext> </mtext> <mtext>ejection</mtext> <mtext> </mtext> <mtext>fraction</mtext> <mtext> </mtext> <mfenced open="(" close=")"> <mrow> <mtext>LVEF</mtext> </mrow> </mfenced> <mo>≥</mo> <mn>40</mn> <mi>%</mi> </math> </jats:inline-formula> without heart failure symptoms were enrolled, and daily injection with liraglutide (0.9 mg) was introduced. Cardiac functions were assessed by TTE before and after 26 weeks of liraglutide treatment. Diastolic cardiac function was defined as septal <jats:inline-formula> <math xmlns="http://www.w3.org/1998/Math/MathML" id="M6"> <mi>E</mi> <mo>/</mo> <msup> <mrow> <mi>E</mi> </mrow> <mrow> <mo>′</mo> </mrow> </msup> <mo>≥</mo> <mn>13.0</mn> </math> </jats:inline-formula>. Results. Thirty-one patients were analyzed. BNP and <jats:inline-formula> <math xmlns="http://www.w3.org/1998/Math/MathML" id="M7"> <mi>E</mi> <mo>/</mo> <msup> <mrow> <mi>E</mi> </mrow> <mrow> <mo>′</mo> </mrow> </msup> </math> </jats:inline-formula> improved, with BNP levels declining from <jats:inline-formula> <math xmlns="http://www.w3.org/1998/Math/MathML" id="M8"> <mn>36.8</mn> <mo>±</mo> <mn>30.5</mn> <mtext> </mtext> <mtext>pg</mtext> <mo>/</mo> <mtext>mL</mtext> </math> </jats:inline-formula> to <jats:inline-formula> <math xmlns="http://www.w3.org/1998/Math/MathML" id="M9"> <mn>26.3</mn> <mo>±</mo> <mn>25.9</mn> <mtext> </mtext> <mtext>pg</mtext> <mo>/</mo> <mtext>mL</mtext> </math> </jats:inline-formula> (<jats:inline-formula> <math xmlns="http://www.w3.org/1998/Math/MathML" id="M10"> <mi>p</mi> <mo>=</mo> <mn>0.0014</mn> </math> </jats:inline-formula>) and <jats:inline-formula> <math xmlns="http://www.w3.org/1998/Math/MathML" id="M11"> <mi>E</mi> <mo>/</mo> <msup> <mrow> <mi>E</mi> </mrow> <mrow> <mo>′</mo> </mrow> </msup> </math> </jats:inline-formula> dropping from <jats:inline-formula> <math xmlns="http://www.w3.org/1998/Math/MathML" id="M12"> <mn>12.7</mn> <mo>±</mo> <mn>4.7</mn> </math> </jats:inline-formula> to <jats:inline-formula> <math xmlns="http://www.w3.org/1998/Math/MathML" id="M13"> <mn>11.0</mn> <mo>±</mo> <mn>3.3</mn> </math> </jats:inline-formula> (<jats:inline-formula> <math xmlns="http://www.w3.org/1998/Math/MathML" id="M14"> <mi>p</mi> <mo>=</mo> <mn>0.0376</mn> </math> </jats:inline-formula>). The LVEF showed no significant changes. <jats:inline-formula> <math xmlns="http://www.w3.org/1998/Math/MathML" id="M15"> <mi>E</mi> <mo>/</mo> <msup> <mrow> <mi>E</mi> </mrow> <mrow> <mo>′</mo> </mrow> </msup> </math> </jats:inline-formula> improved only in patients with <jats:inline-formula> <math xmlns="http://www.w3.org/1998/Math/MathML" id="M16"> <mi>E</mi> <mo>/</mo> <msup> <mrow> <mi>E</mi> </mrow> <mrow> <mo>′</mo> </mrow> </msup> <mo>≥</mo> <mn>13.0</mn> </math> </jats:inline-formula>. Favorable changes in <jats:inline-formula> <math xmlns="http://www.w3.org/1998/Math/MathML" id="M17"> <mi>E</mi> <mo>/</mo> <msup> <mrow> <mi>E</mi> </mrow> <mrow> <mo>′</mo> </mrow> </msup> </math> </jats:inline-formula> were canceled when adjusted for body mass index (BMI). Multivariate linear regression analysis revealed that the left ventricular diastolic diameter and <jats:inline-formula> <math xmlns="http://www.w3.org/1998/Math/MathML" id="M18"> <mo>∆</mo> <mi>E</mi> <mo>/</mo> <msup> <mrow> <mi>E</mi> </mrow> <mrow> <mo>′</mo> </mrow> </msup> </math> </jats:inline-formula>/∆BMI contributed to ∆BNP/baseline BNP (<jats:inline-formula> <math xmlns="http://www.w3.org/1998/Math/MathML" id="M19"> <mi>p</mi> <mo>=</mo> <mn>0.0075</mn> </math> </jats:inline-formula>, <jats:inline-formula> <math xmlns="http://www.w3.org/1998/Math/MathML" id="M20"> <msup> <mrow> <mi>R</mi> </mrow> <mrow> <mn>2</mn> </mrow> </msup> <mo>=</mo> <mn>0.49264</mn> </math> </jats:inline-formula>). Conclusions. Liraglutide had favorable effects on BNP and <jats:inline-formula> <math xmlns="http://www.w3.org/1998/Math/MathML" id="M21"> <mi>E</mi> <mo>/</mo> <msup> <mrow> <mi>E</mi> </mrow> <mrow> <mo>′</mo> </mrow> </msup> </math> </jats:inline-formula> but not on LVEF. <jats:inline-formula> <math xmlns="http://www.w3.org/1998/Math/MathML" id="M22"> <mi>E</mi> <mo>/</mo> <msup> <mrow> <mi>E</mi> </mrow> <mrow> <mo>′</mo> </mrow> </msup> </math> </jats:inline-formula> improvement was only seen in patients with diastolic cardiac function. Body weight reduction affected the change of <jats:inline-formula> <math xmlns="http://www.w3.org/1998/Math/MathML" id="M23"> <mi>E</mi> <mo>/</mo> <msup> <mrow> <mi>E</mi> </mrow> <mrow> <mo>′</mo> </mrow> </msup> </math> </jats:inline-formula>. The BMI-adjusted <jats:inline-formula> <math xmlns="http://www.w3.org/1998/Math/MathML" id="M24"> <mi>E</mi> <mo>/</mo> <msup> <mrow> <mi>E</mi> </mrow> <mrow> <mo>′</mo> </mrow> </msup> </math> </jats:inline-formula> significantly contributed to the relative change of BNP. GLP-1 analog treatment could be considered a therapeutic option against diabetic diastolic cardiac dysfunction regardless of body weight. This trial is registered with the University Hospital Medical Information Network in Japan, with clinical trial registration number: UMIN000005565.</jats:p>