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Exploring appetitive, metabolic and ketotic effects and weight-loss potential of Dapagliflozin in patients with Type 2 Diabetes Mellitus and Obesity, with concomitant dietary intervention
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Hanson, Petra (2021) Exploring appetitive, metabolic and ketotic effects and weight-loss potential of Dapagliflozin in patients with Type 2 Diabetes Mellitus and Obesity, with concomitant dietary intervention. PhD thesis, University of Warwick.
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Official URL: http://webcat.warwick.ac.uk/record=b3733308
Abstract
Background: Type 2 Diabetes Mellitus (T2DM) is closely associated with obesity and increased metabolic risk. Dapagliflozin, the first-in-class of the Sodium Glucose-Like Co-Transporter 2 (SGLT2) inhibitor agents, licensed for use in patients with T2DM, has been demonstrated both on evidence from randomized controlled trials and real-world studies, to be associated with secondary weight-loss and improved cardiovascular outcomes. There have been relatively few studies exploring the metabolic effects of Dapagliflozin and how they relate to weight loss. Moreover, the long-term metabolic adaptations to SGLT2 inhibitors are unknown.
Aims: Our primary objective was to execute detailed phenotyping (metabolic changes, glycosuric response, natriuretic response, changes to appetite, and body composition) in participants with T2DM and obesity, treated with Dapagliflozin therapy and concomitant dietary intervention. We also explored the ketotic potential of Dapagliflozin.
Methodology: Participants underwent detailed metabolic studies, including indirect calorimetry (energy expenditure measurements), quantification of body fat, blood and urine samples analyses and appetite assessments in Metabolic Research Unit located at University Hospitals of Coventry and Warwickshire (UHCW), before, during and after 12-month therapy with Dapagliflozin.
Results: Dapagliflozin therapy resulted in a significant weight loss at 12 months (8.4 kg, p<0.001) driven by a fat loss (8.9 kg, p<0.001), reduction in leptin and insulin levels and reduction in insulin resistance, increase in glucagon levels, glycosuria and urinary volume. There were no changes in appetite, basal metabolic rate, adiponectin levels, fasting glucose and natriuresis. The rise in ketone levels was significant numerically but not clinically, indicating that SGLT2 inhibitor therapy alone does not cause significant ketosis.
Conclusion: Long term treatment with Dapagliflozin leads to significant metabolic changes in patients with T2DM and obesity which are sustained over 12 months and represent mechanisms that could reverse metabolic syndrome.
Item Type: | Thesis (PhD) | ||||
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Subjects: | R Medicine > RC Internal medicine R Medicine > RM Therapeutics. Pharmacology |
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Library of Congress Subject Headings (LCSH): | Type 2 diabetes, Type 2 diabetes -- Treatment, Obesity, Weight loss | ||||
Official Date: | February 2021 | ||||
Dates: |
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Institution: | University of Warwick | ||||
Theses Department: | Warwick Medical School | ||||
Thesis Type: | PhD | ||||
Publication Status: | Unpublished | ||||
Supervisor(s)/Advisor: | Barber, Thomas ; O’Hare, Paul ; Randeva, Harpal S. | ||||
Sponsors: | AstraZeneca (Firm) | ||||
Format of File: | |||||
Extent: | 281 leaves, [20] unnumbered pages : illustrations | ||||
Language: | eng |
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