SEESAW
Research type
Research Study
Full title
SGLT-2 Inhibitor Empagliflozin Effects on Appetite and Weight Regulation: A randomised double-blind placebo-controlled trial (SEESAW)
IRAS ID
178736
Contact name
Melanie Davies
Contact email
Sponsor organisation
University of Leicester
Eudract number
2015-001594-40
Duration of Study in the UK
1 years, 9 months, 0 days
Research summary
Background and Rationale
Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are a novel class of glucose-lowering agents which reduce plasma glucose levels by increasing urinary glucose excretion (UGE) by up to 60-80g (240-320kCal) per day. Weight loss achieved using these agents is less than predicted according to observed calorie loss which is calculated to be approximately 250kCal per day. The mechanism remains unexplained but may involve compensatory changes in appetite regulation and increased energy intake.
Aim
The aim is to investigate the cause for the discrepancy in predicted and observed weight loss with empagliflozin by measuring appetite regulation, energy expenditure and change in weight and body composition.
Methods
We will investigate the effects of empagliflozin on appetite and weight regulation in 76 male and postmenopausal female participants with type 2 diabetes either lifestyle controlled only or on stable dose of metformin in a randomized 4-arm placebo controlled trial over 24 weeks. Participants will be randomized to either empagliflozin 25mg daily, or placebo, or placebo and energy restriction diet, or empagliflozin 25mg daily and energy restriction diet. Appetite regulation will be assessed by measuring appetite hormones including total and acylated ghrelin, glucagon-like peptide 1 (GLP-1) and total Peptide Y-Y (PYY). Other biochemical analysis will include UGE, insulin, glucose, glucagon and leptin. Body composition will be assessed by measuring weight, waist circumference and body fat percentage (using DEXA). Energy expenditure, insulin sensitivity and secretion, and substrate utilisation will be assessed using indirect calorimetry as well as physical activity measures.
Expected Outcomes
The study is expected to show that, compared with placebo, empagliflozin stimulates appetite and increases endogenous glucose production, resulting in less than predicted weight loss despite calorie loss from UGE. As this limits weight loss achieved with SGLT-2 inhibitors, they may need to be combined with energy restriction diets and other glucose-lowering agents for maximal benefit.REC name
East Midlands - Derby Research Ethics Committee
REC reference
16/EM/0040
Date of REC Opinion
19 Apr 2016
REC opinion
Further Information Favourable Opinion