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The effects of empagliflozin, dietary energy restriction, or both on appetite-regulatory gut peptides in individuals with type 2 diabetes and overweight or obesity: the SEESAW randomised, double-blind, placebo-controlled trial

journal contribution
posted on 21.04.2022, 08:43 by Jack Sargeant, James KingJames King, Thomas Yates, Emma Redman, Danielle Bodicoat, Sudesna Chatterjee, Charlotte Edwardson, Laura Gray, Benoit Poulin, Ghazala Waheed, Helen Waller, David Webb, Scott WillisScott Willis, John Wilding, Kamlesh Khunti, David StenselDavid Stensel, Melanie Davies

Aim: To assess the impact of the SGLT2 inhibitor empagliflozin (25mg once-daily), dietary energy restriction, or both combined, on circulating appetite-regulatory peptides in people with type 2 diabetes (T2D) and overweight or obesity. Materials and Methods: In a double-blind, placebo-controlled trial, 68 adults (age 30-75 years) with T2D (drug naïve or on metformin monotherapy; HbA1c 6.0-10.0% [42-86mmol/mol]) and BMI ≥25kg/m2 were randomised to: (1) placebo-only, (2) placebo-plus-diet, (3) empagliflozin-only, or (4) empagliflozin-plus-diet for 24 weeks. Dietary energy restriction matched the estimated energy deficit elicited by SGLT2 inhibitor therapy through urinary glucose excretion (~360kcal/day). The primary outcome was change in postprandial circulating total peptide-YY (PYY) during a 3-hour mixed-meal tolerance test from baseline to 24-weeks. Postprandial total glucagon-like peptide-1 (GLP-1), acylated ghrelin and subjective appetite perceptions formed secondary outcomes, along with other key components of energy balance. Results: The mean weight loss in each group at 24 weeks was 0.44, 1.91, 2.22, and 5.74 kg, respectively. The change from baseline to 24 weeks in postprandial total PYY was similar between experimental groups and placebo-only (mean difference [95% CI]: -8.6: [-28.6 to 11.4], 13.4 [-6.1 to 33.0], and 1.0 [-18.0 to 19.9] pg/mL in placebo-plus-diet, empagliflozin-only, and empagliflozin-plus-diet groups, respectively (all p≥0.18)). Similarly, there was no consistent pattern of difference between groups for post-prandial total GLP-1, acylated ghrelin, and subjective appetite perceptions. Conclusions: In people with T2D and overweight or obesity, changes in postprandial appetite-regulatory gut peptides may not underpin the less-than-predicted weight loss observed with empagliflozin therapy.

History

School

  • Sport, Exercise and Health Sciences

Published in

Diabetes, Obesity and Metabolism

Publisher

Wiley

Version

AM (Accepted Manuscript)

Publisher statement

This is the peer reviewed version of the following article: Sargeant, J.A., King, J.A., Yates, T., Redman, E.L., Bodicoat, D.H., Chatterjee, S., Edwardson, C.L., Gray, L.J., Poulin, B., Waheed, G., Waller, H.L., Webb, D.R., Willis, S.A., Wilding, J.P.H., Khunti, K., Stensel, D.J. and Davies, M.J. (2022), The effects of empagliflozin, dietary energy restriction, or both on appetite-regulatory gut peptides in individuals with type 2 diabetes and overweight or obesity: the SEESAW randomised, double-blind, placebo-controlled trial. Diabetes Obes Metab. Accepted Author Manuscript. https://doi.org/10.1111/dom.14721, which has been published in final form at https://doi.org/10.1111/dom.14721. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.

Acceptance date

18/04/2022

ISSN

1462-8902

eISSN

1463-1326

Language

en

Depositor

Dr James King. Deposit date: 19 April 2022