The Effect of a SGLT2 Inhibitor on Glucose Flux, Lipolysis and Exercise in Type 2 Diabetes

• Status: Completed
• Trial end date: 2020-01-08
• Target enrollment: 0
• Participant gender: All

Summary

The study is a randomised double blind placebo control cross over trial with 4 weeks washout period. The expected duration of participant participation is 103 days. the study aims to investigate the effect of dapagliflozin, a SGLT2 inhibitor, on glucose flux, lipolysis and exercise in patients with type 2 diabetes.

• Phase: Phase 4
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of Leicester
• Collaborators: AstraZeneca; Royal Surrey County Hospital NHS Foundation Trust
• Treatments: 2-(3-(4-ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyltetrahydro-2H-pyran-3,4,5-triol; Dapagliflozin; Sodium-Glucose Transporter 2 Inhibitors

Criteria

Inclusion Criteria:

• • Able in the opinion of the investigator, and willing to give informed consent obtained before any study-related activities.

• Diagnosis of type 2 diabetes greater than 12 months.

• Single, dual or triple therapy glucose lowering agents comprising of sulphonylureas, biguanides and DDP-IV.

• No previous exposure to SGLT2 inhibitors.

• BMI of less than 40.

• HbA1c of greater or equal to 6.5% and less than 9% within 1 month of screening.

• Able to comply with the study and the study procedures.

• Patients who are or who have previously been involved in research are eligible provided a participant has not received an investigational drug within one month of entry into the study.

Exclusion Criteria:

• • Participants over 75.

• Participants under 18.

• Participants who cannot adequately understand verbal and / or written explanations given in English.

• Clinical suspicion of Hypoglycaemic unawareness.

• LADA -latent autoimmune diabetes in adults due to differing nature of the illness/Type 1.

• Confirmed excessive and compulsive drinking of alcohol i.e. alcohol abuse as determined from GP medical notes by the Fast Alcohol Screening Test (FAST) or history of previous alcohol abuse.

• Has a history of chronic pancreatitis.

• Restricted food intake - Determined by history.

• Diagnosis of osteoporosis confirmed by DEXA scan.

• Participants on insulin, insulin analogs or GLP-1 in the preceding 6 months.

• Proliferative retinopathy that has required acute treatment within last three months.

• Moderate to severe renal impairment (creatinine clearance [CrCl] < 60 ml/min or estimated glomerular filtration rate [eGFR] < 60 ml/min/1.73 m2.

• History of unstable or rapidly progressing renal disease.

• Severe hepatic insufficiency / and or significant abnormal liver function defines as aspartate aminotransferase (AST) >3x upper limit of normal (ULN) and / or alanine aminotransferase (ALT) > 3ULN.

• Positive serologic evidence of current infectious liver disease including Hepatitis B viral antibody IGM, Hepatitis B surface antigen and Hepatitis C virus antibody.

• Congestive heart failure defined as New York Heart Association (NYHA) class III and IV, unstable or acute congestive heart failure.

• Uncontrolled cardiac arrhythmias.

• Uncontrolled hypertension. (BP greater than 160/90).

• Mental incapacity.

• Pregnancy or breast feeding women.

• Those of child-bearing potential not taking adequate contraception precautions. Adequate protection is defined as barrier protection, oral contraceptive pill or intrauterine device.

• Volume depleted patients, patients at risk of volume depletion due to co-existing conditions or concomitant medications, such as loop diuretics should have careful monitoring of their volume status.

• History of unstable angina.

• Acute Coronary Syndrome (ACS) within 2 months prior to enrolmen.t

• Hospitalisation for unstable angina or acute myocardial infarction within 2 months prior to enrolment.

• Acute Stroke or TIA within two months prior to enrolment.

• Less than two months post coronary artery revascularisation.

• History of diabetic ketoacidosis (DKA) requiring medical intervention (e.g. emergency room visit and/or hospitalisation) within 1 month prior to the screening visit.

• Known or suspected allergy to study products.

• Known Lactose-intolerant.

• Have severe and enduring mental health problems.

• Are not primarily responsible for their own care