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A randomised, open label, active comparator trial assessing the effects of 26 weeks of Liraglutide or Sitagliptin on cardiovascular function in young obese adults with Type 2 diabetes

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journal contribution
posted on 03.04.2020, 08:56 authored by David Webb, Z Htike, D Swarbrick, Emer Brady, Laura Gray, J Biglands, G Gulsin, J Henson, K Khunti, G McCann, H Waller, M Webb, J Sargeant, T Yates, F Zaccardi, Melanie Davies

Aim To compare the effects of a glucagon‐like peptide‐1 receptor agonist and a dipeptidyl peptidase‐4 inhibitor on magnetic resonance imaging‐derived measures of cardiovascular function.

Materials and methods In a prospective, randomized, open‐label, blinded endpoint trial liraglutide (1.8 mg) and sitagliptin (100 mg) were compared in asymptomatic, non‐insulin treated young (aged 18‐50 years) adults with obesity and type 2 diabetes. The primary outcome was difference in circumferential peak early diastolic strain rate change (PEDSR), a biomarker of cardiac diastolic dysfunction 26 weeks after randomization. Secondary outcomes included other indices of cardiac structure and function, HbA1c and body weight.

Results Seventy‐six participants were randomized (54% female, mean ± SD age 44 ± 6 years, diabetes duration 4.4 years, body mass index 35.3 ± 6.1 kg m−2), of whom 65% had ≥1 cardiovascular risk factor. Sixty‐one participants had primary outcome data available. There were no statistically significant between‐group differences (intention‐to‐treat; mean [95% confidence interval]) in PEDSR change (−0.01 [−0.07, +0.06] s−1), left ventricular ejection fraction (−1.98 [−4.90, +0.94]%), left ventricular mass (+1.14 [−5.23, +7.50] g) or aortic distensibility (−0.35 [−0.98, +0.28] mmHg−1 × 10−3) after 26 weeks. Reductions in HbA1c (−4.57 [−9.10, −0.37] mmol mol−1) and body weight (−3.88 [−5.74, −2.01] kg) were greater with liraglutide.

Conclusion There were no differences in cardiovascular structure or function after short‐term use of liraglutide and sitagliptin in younger adults with obesity and type 2 diabetes. Longer studies in patients with more severe cardiac dysfunction may be necessary before definitive conclusions can be made about putative pleiotropic properties of incretin‐based therapies.

Funding

The study was supported by the NIHR Leicester Biomedical Research Center (BRC), the NIHR CLAHRC‐East Midlands, the NIHR Leicester Clinical Research Facility and The NIHR Leicester Clinical Trial Unit (CTU). GPM was supported by NIHR postdoctoral (2011‐04‐51) and career development fellowships (2014‐07‐045).

Novo Nordisk Investigator‐sponsored study

History

Citation

Diabetes Obes Metab. 2020;1 –10.

Author affiliation

College of Life Sciences

Version

VoR (Version of Record)

Published in

Diabetes, Obesity and Metabolism: a journal of pharmacology and therapeutics

Publisher

Wiley

issn

1462-8902

eissn

1463-1326

Acceptance date

05/03/2020

Copyright date

2020

Publisher version

https://dom-pubs.onlinelibrary.wiley.com/doi/full/10.1111/dom.14023

Language

en