Amelioration of pancreatic fat accumulation in Japanese type 2 diabetes patients treated with sodium‐glucose cotransporter 2 inhibitors: a retrospective study

Abstract

Background: Prior reports have suggested that pancreatic fat is related to type 2 diabetes. Sodium-glucose co-transporter-2 (SGLT-2) inhibitors are expected to reduce ectopic fat accumulation.Aim: This study assessed the effect of SGLT-2 inhibitors on pancreatic and liver fat accumulations in patients with type 2 diabetes. Materials and Methods:Retrospective analyses of indices of pancreatic and liver fat accumulations were conducted in 22 type 2 diabetes outpatients who were receiving SGLT-2 inhibitors for more than 12 weeks. The differences between the pancreatic (P) or liver (L) and splenic (S) computed tomography values were evaluated.Results: Fatty pancreas was defined as PÀ S < À 8 Hounsfield Unit (HU), and the number of patients with fatty pancreas was 11 (50%). Fatty pancreas significantly improved after SGLT-2 inhibitor use (median, À 20.8; IQR, À 34.8 to À 14.3 HU vs. median, À 14.6; IQR, À 29.5 to À 7.8 HU; p ¼ 0.041). Fatty liver was defined as LÀ S ≤ 3.9 HU, and the number of patients with fatty liver was 11 (50%). Fatty liver significantly improved after SGLT-2 inhibitor use (median, À 4.3; IQR, À 23.0 to 3.0 HU vs. median, À 0.7; IQR, À 5.2 to 6.3 HU; p ¼ 0.016). Conclusion:Pancreatic fat and liver fat accumulations might be reduced after treatment with SGLT-2 inhibitors in type 2 diabetes patients with intense cumulative fat depositions in these organs. K E Y W O R D S pancreatic fat, SGLT-2 inhibitor, terms: type 2 diabetesThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Ectopic Fat Accumulation in Pancreas and Heart

“…Considering these reports, GLP-1RA, SGLT-2 inhibitors, and PPARα agonists might have the possibility that they also reduce pancreatic fat accumulation, resulting in the improvement of diabetic pathophysiology and pancreatic carcinogenesis. We enrolled 22 type 2 diabetic outpatients, who had undergone unenhanced abdominal CT examinations before and more than 3 months after SGLT-2 inhibitor administration, and investigated the changes of the degrees of liver and pancreatic fat accumulations [30]. As a result, no improvement in these fat accumulations was observed in total.…”

“…On the other hand, it has been reported that excess epicardial fat is involved in lipotoxicity due to supplying excess free fatty acids, cardiac hypertrophy, and cardiac diastolic dysfunction [31]. Epicardial fat is increased in patients with type 2 diabetes [30,31], and its accumulation has been reported to be associated with the presence of coronary artery disease [32,33].…”

The Pharmacological Landscape for Fatty Change of the Pancreas

“…Five (four prospective and one retrospective) clinical studies investigated changes in IPFD following the administration of SGLT-2 inhibitors in individuals with T2DM or prediabetes [ 42 – 46 ]. In addition to SGLT-2 inhibitors, individuals with T2DM received other glucose-lowering medications (including insulin in two studies [ 42 , 43 ]).…”

“…Five (four prospective and one retrospective) clinical studies investigated changes in IPFD following the administration of SGLT-2 inhibitors in individuals with T2DM or prediabetes [ 42 – 46 ]. In addition to SGLT-2 inhibitors, individuals with T2DM received other glucose-lowering medications (including insulin in two studies [ 42 , 43 ]). The retrospective study identified 22 individuals in Japan over a 6-year study period and found no significant difference in IPFD (determined with the use of computed tomography) before and after administration of SGLT-2 inhibitors [ 42 ].…”

“…In addition to SGLT-2 inhibitors, individuals with T2DM received other glucose-lowering medications (including insulin in two studies [ 42 , 43 ]). The retrospective study identified 22 individuals in Japan over a 6-year study period and found no significant difference in IPFD (determined with the use of computed tomography) before and after administration of SGLT-2 inhibitors [ 42 ]. All the four prospective studies used a magnetic resonance system at 3T to determine IPFD and the sample size of these studies ranged from 30 to 78 individuals [ 43 – 46 ].…”