drugset / Trial / NCT02798744
SGLT-2 Inhibitor Empagliflozin Effects on Appetite and Weight Regulation.
Phase 4
Completed
68 enrolled
University of Leicester
Loughborough University · collabUniversity Hospitals, Leicester · collab
RandomizedParallel-groupQuadruple-blindTreatment
Summary
The aim of this study is to investigate the cause for the discrepancy in predicted and observed weight loss with Empagliflozin (Jardiance™) by measuring appetite regulation. Major secondary objectives are to determine the effects of Empagliflozin (Jardiance™) on energy expenditure and change in total body weight and body composition. The primary outcome is change in appetite hormone concentrations (specifically total PYY) between baseline and 24 weeks: - this will be measured by sequential blood sampling during visits 1-5. Secondary outcomes, which are exploratory, are effect on appetite hormones (ghrelin and GLP-1), appetite perceptions, total body weight and fat and fat free mass, energy expenditure, appetite perception, physical activity and blood and urine biochemical parameters after Empagliflozin (Jardiance™) treatment for 24 weeks. The sample size for the study is 76 participants and the planned trial duration is 21 months, with participants receiving approximately 24 weeks of exposure to Empagliflozin (Jardiance™).
Timeline
- Start
- 2016-12
- Primary completion
- 2019-07-30
- Completion
- 2019-07-30
Outcome
Missed primary endpoint
paper The change from baseline to 24 weeks in postprandial total PYY was similar between experimental groups and placebo only PMID 35441435 ↗
paper 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 ≥ .18]. PMID 35441435 ↗
Publications
- Background Bailey CJ. Renal glucose reabsorption inhibitors to treat diabetes. Trends Pharmacol Sci. 2011 Feb;32(2):63-71. doi: 10.1016/j.tips.2010.11.011. Epub 2011 Jan 4.
- Background Bailey CJ. SGLT2 inhibitors:Glucuretic treatment for type 2 diabetes. British Journal of Diabetes and Vascular Disease. 2010;10:193-199
- Background Hasan FM, Alsahli M, Gerich JE. SGLT2 inhibitors in the treatment of type 2 diabetes. Diabetes Res Clin Pract. 2014 Jun;104(3):297-322. doi: 10.1016/j.diabres.2014.02.014. Epub 2014 Mar 11.
- Background Bolinder J, Ljunggren O, Kullberg J, Johansson L, Wilding J, Langkilde AM, Sugg J, Parikh S. Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin. J Clin Endocrinol Metab. 2012 Mar;97(3):1020-31. doi: 10.1210/jc.2011-2260. Epub 2012 Jan 11.
- Background Broom DR, Batterham RL, King JA, Stensel DJ. Influence of resistance and aerobic exercise on hunger, circulating levels of acylated ghrelin, and peptide YY in healthy males. Am J Physiol Regul Integr Comp Physiol. 2009 Jan;296(1):R29-35. doi: 10.1152/ajpregu.90706.2008. Epub 2008 Nov 5.
- Background Ferrannini E, Seman L, Seewaldt-Becker E, Hantel S, Pinnetti S, Woerle HJ. A Phase IIb, randomized, placebo-controlled study of the SGLT2 inhibitor empagliflozin in patients with type 2 diabetes. Diabetes Obes Metab. 2013 Aug;15(8):721-8. doi: 10.1111/dom.12081. Epub 2013 Mar 4.
- Background Ferrannini E, Muscelli E, Frascerra S, Baldi S, Mari A, Heise T, Broedl UC, Woerle HJ. Metabolic response to sodium-glucose cotransporter 2 inhibition in type 2 diabetic patients. J Clin Invest. 2014 Feb;124(2):499-508. doi: 10.1172/JCI72227. Epub 2014 Jan 27.
- Background Ferrannini G, Hach T, Crowe S, Sanghvi A, Hall KD, Ferrannini E. Energy Balance After Sodium-Glucose Cotransporter 2 Inhibition. Diabetes Care. 2015 Sep;38(9):1730-5. doi: 10.2337/dc15-0355. Epub 2015 Jul 15.
- Background Haring HU, Merker L, Seewaldt-Becker E, Weimer M, Meinicke T, Woerle HJ, Broedl UC; EMPA-REG METSU Trial Investigators. Empagliflozin as add-on to metformin plus sulfonylurea in patients with type 2 diabetes: a 24-week, randomized, double-blind, placebo-controlled trial. Diabetes Care. 2013 Nov;36(11):3396-404. doi: 10.2337/dc12-2673. Epub 2013 Aug 20.
- Background Haring HU, Merker L, Seewaldt-Becker E, Weimer M, Meinicke T, Broedl UC, Woerle HJ; EMPA-REG MET Trial Investigators. Empagliflozin as add-on to metformin in patients with type 2 diabetes: a 24-week, randomized, double-blind, placebo-controlled trial. Diabetes Care. 2014 Jun;37(6):1650-9. doi: 10.2337/dc13-2105. Epub 2014 Apr 10.
- Background Kovacs CS, Seshiah V, Swallow R, Jones R, Rattunde H, Woerle HJ, Broedl UC; EMPA-REG PIO trial investigators. Empagliflozin improves glycaemic and weight control as add-on therapy to pioglitazone or pioglitazone plus metformin in patients with type 2 diabetes: a 24-week, randomized, placebo-controlled trial. Diabetes Obes Metab. 2014 Feb;16(2):147-58. doi: 10.1111/dom.12188. Epub 2013 Aug 22.
- Background Madsbad S. The role of glucagon-like peptide-1 impairment in obesity and potential therapeutic implications. Diabetes Obes Metab. 2014 Jan;16(1):9-21. doi: 10.1111/dom.12119. Epub 2013 May 26.
- Background Merovci A, Solis-Herrera C, Daniele G, Eldor R, Fiorentino TV, Tripathy D, Xiong J, Perez Z, Norton L, Abdul-Ghani MA, DeFronzo RA. Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production. J Clin Invest. 2014 Feb;124(2):509-14. doi: 10.1172/JCI70704. Epub 2014 Jan 27.
- Background Mifflin MD, St Jeor ST, Hill LA, Scott BJ, Daugherty SA, Koh YO. A new predictive equation for resting energy expenditure in healthy individuals. Am J Clin Nutr. 1990 Feb;51(2):241-7. doi: 10.1093/ajcn/51.2.241.
- Background Rahmoune H, Thompson PW, Ward JM, Smith CD, Hong G, Brown J. Glucose transporters in human renal proximal tubular cells isolated from the urine of patients with non-insulin-dependent diabetes. Diabetes. 2005 Dec;54(12):3427-34. doi: 10.2337/diabetes.54.12.3427.
- Background Ridderstrale M, Andersen KR, Zeller C, Kim G, Woerle HJ, Broedl UC; EMPA-REG H2H-SU trial investigators. Comparison of empagliflozin and glimepiride as add-on to metformin in patients with type 2 diabetes: a 104-week randomised, active-controlled, double-blind, phase 3 trial. Lancet Diabetes Endocrinol. 2014 Sep;2(9):691-700. doi: 10.1016/S2213-8587(14)70120-2. Epub 2014 Jun 16.
- Background Roden M, Weng J, Eilbracht J, Delafont B, Kim G, Woerle HJ, Broedl UC; EMPA-REG MONO trial investigators. Empagliflozin monotherapy with sitagliptin as an active comparator in patients with type 2 diabetes: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Diabetes Endocrinol. 2013 Nov;1(3):208-19. doi: 10.1016/S2213-8587(13)70084-6. Epub 2013 Sep 9.
- Background Rosenstock J, Jelaska A, Frappin G, Salsali A, Kim G, Woerle HJ, Broedl UC; EMPA-REG MDI Trial Investigators. Improved glucose control with weight loss, lower insulin doses, and no increased hypoglycemia with empagliflozin added to titrated multiple daily injections of insulin in obese inadequately controlled type 2 diabetes. Diabetes Care. 2014 Jul;37(7):1815-23. doi: 10.2337/dc13-3055. Epub 2014 Jun 14.
- Background Sumithran P, Prendergast LA, Delbridge E, Purcell K, Shulkes A, Kriketos A, Proietto J. Long-term persistence of hormonal adaptations to weight loss. N Engl J Med. 2011 Oct 27;365(17):1597-604. doi: 10.1056/NEJMoa1105816.
- Background Tahrani AA, Barnett AH, Bailey CJ. SGLT inhibitors in management of diabetes. Lancet Diabetes Endocrinol. 2013 Oct;1(2):140-51. doi: 10.1016/S2213-8587(13)70050-0. Epub 2013 Aug 13.
- Background Vasilakou D, Karagiannis T, Athanasiadou E, Mainou M, Liakos A, Bekiari E, Sarigianni M, Matthews DR, Tsapas A. Sodium-glucose cotransporter 2 inhibitors for type 2 diabetes: a systematic review and meta-analysis. Ann Intern Med. 2013 Aug 20;159(4):262-74. doi: 10.7326/0003-4819-159-4-201308200-00007.
- Sargeant JA, King JA, Yates T, Redman EL, Bodicoat DH, Chatterjee S, Edwardson CL, Gray LJ, Poulin B, Waheed G, Waller HL, Webb DR, Willis SA, Wilding JPH, Khunti K, Stensel DJ, Davies MJ. 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 randomized, double-blind, placebo-controlled trial. Diabetes Obes Metab. 2022 Aug;24(8):1509-1521. doi: 10.1111/dom.14721. Epub 2022 May 13.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Empagliflozin | Small molecule | 25 mg | Oral |