Effects of Liraglutide in Young Adults With Type 2 DIAbetes (LYDIA)

NCT02043054 | Completed Phase 3 DMC

• 3 other identifiers: 03982012-002422-78U1111-1131-8802
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

There are recent advances in therapies for the treatment of Type 2 Diabetes Mellitus (T2DM) which include the GLP1 analogues and the DPP IV inhibitors. Both of these therapies target the incretin system using different methods to elevate/maintain circulating levels of GLP1 to subsequently achieve improved blood sugar control. Interestingly, GLP1 analogues have been reported not only to improve blood sugar control but to additionally induce weight-loss and emerging experimental evidence has shown it may have beneficial effects on the heart's structure and function. Due to the profile of this condition being a lot worse and younger patients having greater CVD risk, a therapy offering multiple positive effects, in particular the potential cardiometabolic effects, make this line of therapy attractive in this patient population. The aim of this research is to investigate the cardiometabolic effects of Liraglutide (GLP1 analogue) compared to that of its clinically relevant comparator Sitagliptin (DPP IV inhibitor).

Conditions

Type 2 Diabetes Mellitus; Cardiovascular Disease

Keywords

Type 2 Diabetes Mellitus (T2DM); Young Adults; Cardiovascular Disease (CVD); GLP1 Analogue; DPP IV Inhibitor; Obesity; Cardiometabolic Effects; Cardiac MRI

Outcome Measures

Primary Outcomes (1)

• Change in peak early diastolic strain rate measured by cardiac MRI

  It is now well recognised that diastolic dysfunction is the primary characteristic of heart disease in T2DM. Measured by gold-standard tagged cardiac MRI. MRI scans will be anonymised and sent to a stand-alone work station for independent analysis.

  Change from baseline peak end diastolic strain rate at 26 weeks

Secondary Outcomes (13)

• Composite of standard biochemical variables

  Changes from baseline to 26 weeks

• Composite chronic low-grade inflammation and adiposity

  Changes from baseline to 26 weeks

• Composite Endothelial Function

  Changes from Baseline to 26 weeks

• Composite Standard Anthropometric variables

  Changes from baseline to 26 weeks

• MRI defined adiposity

  Changes from baseline to 26 weeks

Study Arms (2)

Liraglutide

EXPERIMENTAL

Liraglutide doses will be self-administered by the participant through daily subcutaneous injections. Liraglutide doses will be initiated at 0.6 mg and then increased to 1.2 mg in week two and 1.8mg in week three. The dose will then be maintained at 1.8 mg. Where 1.8 mg doses are not tolerated by the patient, the dose will be lowered to the maximum tolerated dose at the investigators discretion.

Drug: Liraglutide

Sitagliptin

ACTIVE COMPARATOR

Sitagliptin doses will be self-administered by the participant orally at 100mg/day throughout the 26 week period of the study. Sitagliptin is licensed to be used either alone or in combination with other oral antihyperglycemic agents (such as metformin or a sulphonylurea)

Drug: Sitagliptin

Interventions

Liraglutide DRUG

Liraglutide (Victoza®, Novo Nordisk) is a stable analogue of the natural hormone glucagon-like peptide-1 (GLP-1). Liraglutide is licensed for use within the United Kingdom and recommended by NICE in combination with metformin, and/or sulphonylurea and/or thiazolidinedione if the following conditions are satisfied. * BMI ≥ 35 kg/m2 in those of European descent (with appropriate adjustment for other ethnic groups) and specific psychological or medical problems associated with high body weight, or * BMI \< 35 kg/m2, and therapy with insulin would have significant occupational implications or weight loss would benefit other significant obesity-related comorbidities.

Also known as: Victoza

Liraglutide

Sitagliptin DRUG

Sitagliptin (Januvia®, Merck \& Co) is an enzyme-inhibiting drug used to inhibit the natural enzyme dipeptidyl peptidase-4 (DPP-4). It is an oral antihyperglycaemic agent used in the treatment of T2DM. Sitagliptin is licensed to be used either alone or in combination with other oral antihyperglycemic agents (such as metformin or a sulphonylurea) and is recommended by NICE as a second line therapy.

Also known as: Januvia

Sitagliptin

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Capacity to provide informed consent before any trial-related activities
• Individuals aged 18 - 60 years inclusive
• Established T2DM
• BMI ≥ 30 kg/m2 (≥27 kg/m2 for South Asians or other BME populations)
• On mono or combination oral OAD therapy (sulphonylurea and/or metformin) for ≥ 3months
• No prescribed thiazolidinediones within the last 3 months
• An HbA1c value of greater than or equal to 6.5% and less than 10%

You may not qualify if:

• \< 18 years old
• Absolute contraindications to MRI
• Type 1 diabetes (identified through C-peptide analysis)
• Females of child bearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods
• Suffer from terminal illness
• Have impaired renal function (eGFR \< 30 ml/min/1.73m2) )
• Impaired liver function (ALAT≥2.5 times upper limit of normal)
• Known to be Hepatitis B antigen or Hepatitis C antibody positive
• Clinically significant active cardiovascular disease including history of myocardial infarction within the past 6 months and/or heart failure (NYHA class III and IV) at the discretion of the investigator
• Recurrent major hypoglycaemia as judged by the investigator
• Known or suspected allergy to the trial products
• Known or suspected thyroid disease
• Receipt of any investigational drug within four weeks prior to this trial
• Have severe and enduring mental health problems
• Are not primarily responsible for their own care

Sponsors & Collaborators

• University of Leicester: lead
• Novo Nordisk A/S: collaborator
• University Hospitals, Leicester: collaborator

Study Sites (1)

University Hospitals of Leicester NHS Trust, Diabetes Research Centre

Leicester, Leicestershire, LE5 4PW, United Kingdom

Location

Related Publications (1)

• Htike ZZ, Yates T, Brady EM, Webb D, Gray LJ, Swarbrick D, McCann GP, Khunti K, Davies MJ. 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). Cardiovasc Diabetol. 2016 Jul 21;15(1):102. doi: 10.1186/s12933-016-0421-6.

  PMID: 27440110 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Cardiovascular Diseases; Obesity

Interventions

Liraglutide; Sitagliptin Phosphate

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines

Study Officials

• Melanie Davies, Prof

  University of Leicester

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2014
• First Posted: January 23, 2014
• Study Start: December 16, 2013
• Primary Completion: September 2, 2017
• Study Completion: September 29, 2017
• Last Updated: January 30, 2020

Record last verified: 2016-11

Locations

GB (1)