The DAPA-DIET study: Metabolic response to Dapagliflozin combined with dietary carbohydrate restriction in patients with Type 2 Diabetes Mellitus and Obesity-A longitudinal cohort study



Hanson, Petra, Randeva, Harpal, Cuthbertson, Dan J ORCID: 0000-0002-6128-0822, O'Hare, Paul J, Parsons, Nick, Chatha, Kamaljit, Reidy, Gemma, Weickert, Martin O and Barber, Thomas M
(2022) The DAPA-DIET study: Metabolic response to Dapagliflozin combined with dietary carbohydrate restriction in patients with Type 2 Diabetes Mellitus and Obesity-A longitudinal cohort study. ENDOCRINOLOGY DIABETES & METABOLISM, 5 (6). e381-.

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Abstract

<h4>Objective</h4>The cardio-renal benefits of sodium glucose-like transporter 2 inhibitor (SGLT2i) therapies have been demonstrated in patients with and without type 2 diabetes. However, no studies have explored the long-term metabolic effects of SGLT2i, combined with dietary carbohydrate restriction. Our primary objective was to describe long-term changes in weight, energy expenditure, appetite and body composition after 12 months of Dapagliflozin therapy, with carbohydrate restriction, in people with type 2 diabetes and obesity. Our secondary objective was to assess changes in adiponectin and leptin.<h4>Method</h4>This was a 12-month cohort study in a secondary care setting. Participants (n = 18) with type 2 diabetes (T2D) and class 3 obesity underwent baseline indirect calorimetry for determination of 24-h energy expenditure, body composition, fasting serum leptin and adiponectin levels, and appetitive assessments. Following initiation of Dapagliflozin (and dietary carbohydrate restriction), measurements were repeated at monthly intervals up to 12 months.<h4>Results</h4>Mean starting weight of participants was 129.4 kg (SD 25.9), mean BMI 46.1 kg/m<sup>2</sup> (SD 8.3) and mean HbA1c 53.9 mmol/mol (14.1). Seventeen participants completed the study; after 12 months of Dapagliflozin and dietary carbohydrate restriction, mean weight loss was 8.1 kg (SD 11.3 kg; p = .009). This was mediated by reduced fat mass (mean loss, 9.9 kg; SD 10.4 kg; p = .002) associated with reduced serum leptin at 12 months (mean reduction 11,254 pg/ml; SD 16,075; p = .011). There were no significant changes in self-reported appetite, 24-h energy expenditure or serum adiponectin during follow-up.<h4>Conclusion</h4>In this study, combined Dapagliflozin therapy and carbohydrate restriction in patients with T2D and obesity resulted in a significant reduction of body weight and fat mass at 12 months without any discernible changes in energy expenditure or appetite. These results offer a scientific and clinical rationale to conduct an exploratory trial investigating the effects of a low carbohydrate diet combined with SGLT2 inhibitors in patients with T2D.

Item Type: Article
Uncontrolled Keywords: appetite, carbohydrate restriction, energy expenditure, fat mass, lean mass, metabolism, SGLT2 inhibitor, type 2 diabetes
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences
Depositing User: Symplectic Admin
Date Deposited: 31 Jan 2023 09:06
Last Modified: 31 Jan 2023 09:06
DOI: 10.1002/edm2.381
Open Access URL: https://doi.org/10.1002/edm2.381
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URI: https://livrepository.liverpool.ac.uk/id/eprint/3167982