Introduction: Pancreatic fat accumulation is a potential pathogenic factor in type 2 diabetes. Evidence from hypocaloric diet indicates that reduction of pancreatic fat could contribute to an improvement in ß-cell function. There is no established pharmacological approach to reduce pancreatic steatosis. We now tested the ability of empagliflozin to reduce pancreatic fat content in overweight and obese persons with prediabetes.
Methods: In this double-blind, placebo-controlled randomized trial (NCT03227484) , 40 participants were 1:1 randomized to receive 25 mg empagliflozin qd or placebo for 8 weeks. Pancreatic fat was quantified by magnetic resonance imaging (6-point Dixon technique) . Insulin sensitivity and insulin secretion was estimated from 75g oral glucose tolerance test. The study was adequately powered to detect effects on pancreatic fat previously reported from the DiRECT trial.
Results: There was no significant change in pancreatic fat content in either treatment group (empagliflozin group -0.88 % ± 2.71 %, placebo group 0.22 % ± 3.02 % [mean±SD], both p≥0.2) and the course of pancreatic fat content was comparable between treatments (p=0.2) . Insulin secretion, as assessed by Disposition Index and AUC-C-peptide0-30/AUC-glucose0-30 (adjusted for insulin sensitivity) did not differ between treatments (p=0.3 and p=0.7, respectively) .
Discussion: This randomized, controlled trial did not detect effects of empagliflozin on pancreatic fat content and insulin secretion in persons with prediabetes. This implicates that the beneficial effects of empagliflozin on liver fat and systemic glucose metabolism do not rely on alterations in pancreatic fat. Consequently, further options for pancreatic fat reduction need to be evaluated.
J.Hummel: None. M.Heni: Advisory Panel; Boehringer Ingelheim International GmbH, Research Support; Boehringer Ingelheim International GmbH, Sanofi, Speaker's Bureau; Amryt Pharma Plc, Boehringer Ingelheim International GmbH, Novo Nordisk. J.Machann: None. C.Dannecker: None. S.Kullmann: Other Relationship; Novo Nordisk. A.L.Birkenfeld: None. H.Häring: None. A.Peter: None. A.Fritsche: Advisory Panel; Boehringer Ingelheim International GmbH, Novo Nordisk, Sanofi-Aventis Deutschland GmbH. R.Wagner: Advisory Panel; Akcea Therapeutics, Daiichi Sankyo, Sanofi-Aventis Deutschland GmbH, Speaker's Bureau; Lilly, Novo Nordisk, Sanofi-Aventis Deutschland GmbH.
This study was supported by Boehringer Ingelheim through an Independent Research Grant. Boehringer Ingelheim had role in the study design, in the collection, analysis or interpretation of data, or in writing of this abstract.