title: Rationale and design of the randomised controlled trial to assess the impact of liraglutide on cardiac function and structure in young adults with type 2 diabetes (the LYDIA study).
abstract: The prevalence of type 2 diabetes (T2DM) in younger adults is growing. Compared to the late onset T2DM, it is well recognized that the disease tends to behave more aggressively in the younger age group with evidence of premature micro and macrovasular diseases and shorter life span. This increased mortality is largely attributed to cardiovascular complications. In a recent pilot study, young adults with T2DM were found to have significantly lower peak diastolic strain rate (PEDSR) on cardiac MRI (CMR), a forerunner of diabetic cardiomyopathy. Liraglutide, a glucagon like peptide-1 (GLP-1) analogue, is one of the new classes of glucose lowering therapies licensed to be used in management of T2DM. In randomised controlled trials, liraglutide improves glycaemic control by 1-1.5 % with an added benefit of weight loss of 2-3 kg. In addition, there is emerging evidence elucidating the cardioprotective effects of GLP-1 analogues independent of glycaemic control. In a small study, liraglutide has also been shown to improve cardiac function in patients with coronary ischaemia or congestive heart failure.
  
  
  
  This is a prospective, randomised, open-label, blind end-point (PROBE) active-comparator trial. A total of 90 obese eligible participants with T2DM (18-50 years) will be randomised to either liraglutide 1.8 mg once daily or sitagliptin 100 mg once daily for 26 weeks. The primary aim is to assess whether liraglutide improves diastolic function compared to sitagliptin as measured by PEDSR using CMR.
  
  
  
  Although newer classes of GLP-1 analogues are made available in recent years, there are very few published studies demonstrating the beneficial effect of GLP-1 analogues on cardiovascular endpoints. In a recently published LEADER study, liraglutide has shown superiority to placebo in a population of type 2 diabetes with high risk of cardiovascular disease. To the best of our knowledge, there are no published studies establishing the effect of liraglutide on cardiac function in younger patients with T2DM on a larger scale. The LYDIA study will comprehensively describe changes in various parameters of cardiac structure and function in patients treated with liraglutide aiming to provide new evidence on effect of liraglutide on diastolic function in young obese people with T2DM. Trial Registration ClinicalTrials.gov identifier: NCT02043054.
authors.affiliation: NIHR Leicester-Loughborough Diet, Lifestyle and Physical Activity Biomedical Research Unit, Leicester Diabetes Centre, Leicester General Hospital, Leicester, UK and Health Sciences, University of Leicester, Leicester, UK. zzhtike@gmail.com.
authors.forename: Z Z
authors.initials: ZZ
authors.lastname: Htike
authors.affiliation: NIHR Leicester-Loughborough Diet, Lifestyle and Physical Activity Biomedical Research Unit, Leicester Diabetes Centre, Leicester General Hospital, Leicester, UK and Health Sciences, University of Leicester, Leicester, UK.
authors.forename: T
authors.initials: T
authors.lastname: Yates
authors.affiliation: NIHR Leicester-Loughborough Diet, Lifestyle and Physical Activity Biomedical Research Unit, Leicester Diabetes Centre, Leicester General Hospital, Leicester, UK and Health Sciences, University of Leicester, Leicester, UK.
authors.forename: E M
authors.initials: EM
authors.lastname: Brady
authors.affiliation: NIHR Leicester-Loughborough Diet, Lifestyle and Physical Activity Biomedical Research Unit, Leicester Diabetes Centre, Leicester General Hospital, Leicester, UK and Health Sciences, University of Leicester, Leicester, UK.
authors.forename: D
authors.initials: D
authors.lastname: Webb
authors.affiliation: NIHR Leicester-Loughborough Diet, Lifestyle and Physical Activity Biomedical Research Unit, Leicester Diabetes Centre, Leicester General Hospital, Leicester, UK and Health Sciences, University of Leicester, Leicester, UK.
authors.forename: L J
authors.initials: LJ
authors.lastname: Gray
authors.affiliation: Department of Cardiovascular Sciences, Glenfield Hospital, University of Leicester, Leicester, UK.|NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK.
authors.forename: D
authors.initials: D
authors.lastname: Swarbrick
authors.affiliation: Department of Cardiovascular Sciences, Glenfield Hospital, University of Leicester, Leicester, UK.|NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK.
authors.forename: G P
authors.initials: GP
authors.lastname: McCann
authors.affiliation: NIHR Leicester-Loughborough Diet, Lifestyle and Physical Activity Biomedical Research Unit, Leicester Diabetes Centre, Leicester General Hospital, Leicester, UK and Health Sciences, University of Leicester, Leicester, UK.
authors.forename: K
authors.initials: K
authors.lastname: Khunti
authors.affiliation: NIHR Leicester-Loughborough Diet, Lifestyle and Physical Activity Biomedical Research Unit, Leicester Diabetes Centre, Leicester General Hospital, Leicester, UK and Health Sciences, University of Leicester, Leicester, UK.
authors.forename: M J
authors.initials: MJ
authors.lastname: Davies
mesh_terms: D000328:Adult; D000368:Aged; D002318:Cardiovascular Diseases / Q000150:complications / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D000069450:Liraglutide / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000188:drug therapy*; D010865:Pilot Projects; D055815:Young Adult
chemical_list: D007004:Hypoglycemic Agents; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1
keywords: Cardiac MRI; Cardiac function; Liraglutide; Type 2 diabetes