Empagliflozin versus sitagliptin for ameliorating intrahepatic lipid content and tissue‐specific insulin sensitivity in patients with early‐stage type 2 diabetes with non‐alcoholic fatty liver disease: A prospective randomized study

Abstract

Aim: To compare the effects of sodium-glucose co-transporter-2 (SGLT2) inhibitors and dipeptidyl peptidase-4 inhibitors on ectopic fat accumulation and tissue-specific insulin sensitivity. Materials and Methods:This randomized controlled trial enrolled 44 patients with type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD). They were randomly assigned to receive either empagliflozin 10 mg/day or sitagliptin 100 mg/day for 12 weeks. The primary endpoint was the change in intrahepatic lipid content (IHL) measured using proton magnetic resonance spectroscopy ( 1 H-MRS). The secondary endpoints included intramuscular and extramuscular lipid content seen in 1 H-MRS, body composition seen through dual-energy X-ray absorptiometry and tissue-specific insulin sensitivity shown through hyperinsulinaemic-euglycaemic clamp using stable isotopic glucose. Liver biopsy samples were pathologically evaluated at baseline. Results: At baseline, the mean duration of diabetes, HbA1c level and IHL were 3.7 years, 7.2% and 20.9%, respectively. The median NAFLD activity score was 3.0.IHL was significantly more decreased in the empagliflozin group than that in the sitagliptin group (between-group difference was À5.2% ± 1.1% and À1.9% ± 1.2%, respectively, (95% confidence interval); À3.3 (À6.5, À0.1), P = .044). However, there were no significant between-group differences in the change of insulin sensitivity in the liver, muscle or adipose tissues. Interestingly, hepatic insulin sensitivity was significantly increased only in the empagliflozin group and was significantly negatively associated with the change in IHL.Conclusions: Empagliflozin significantly improves hepatic steatosis compared with sitagliptin, and this may protect against subsequent hepatic insulin resistance. Early administration of SGLT2 inhibitors is preferable for T2D patients with NAFLD.

Comparative effectiveness of sodium‐glucose co‐transporter‐2 inhibitors and dipeptidyl peptidase‐4 inhibitors on liver function in patients with type 2 diabetes in Japan: A real‐world data analysis

“…These may partly be explained by the higher baseline ALT in patients receiving an SGLT2i than in those receiving a DPP4i among both the overall population (Table 1) and within these subgroups (Table S4). Additionally, SGLT2is have been associated with a significant intrahepatic lipid content reduction, with increased hepatic insulin sensitivity, compared with DPP4is 31 . Together with this report, these results suggest that early SGLT2i initiation in patients with normal liver function or early‐stage liver disease may improve hepatic steatosis and prevent hepatic insulin resistance, ultimately preventing hepatic steatosis from progressing to liver fibrosis.…”

Effects of Incretin-Based Treatment on the Diastolic (Dys)Function in Patients with Uncontrolled Type 2 Diabetes Mellitus: A Prospective Study with 1-Year Follow-Up

“…For instance, in a parallel group trial enrolling 44 Japanese patients with T2DM, echocardiographic changes were assessed after 12 weeks of treatment with either sitagliptin or empagliflozin. While LVEF and percentage fractional shortening (%FS) decreased significantly more in the sitagliptin group (p < 0.05), no significant differences were found regarding E/e' and E/A [28].…”

Unlocking liver health: Can tackling myosteatosis spark remission in metabolic dysfunction‐associated steatotic liver disease?

“…EGF also decreased total adiposity, liver fat assessed by 1 H‐MRS and hepatic insulin resistance specifically measured by hyperinsulinaemic‐euglycaemic clamp 102 . No impact on IMCL and EMCL of tibialis anterior measured by 1 H‐MRS was reported 102 . Interestingly, both SGLT‐2 inhibitors decreased lean muscle mass measured by CT (CGF) 101 and dual‐energy X‐ray absorptiometry (EGF) 102 (Figure 3).…”

“…Empagliflozin (EGF), another SGLT‐2 inhibitor, was also investigated in a cohort of 23 overweight patients with MASLD and type 2 diabetes at the dose of 10 mg/day for a period of 3 months 102 . EGF also decreased total adiposity, liver fat assessed by 1 H‐MRS and hepatic insulin resistance specifically measured by hyperinsulinaemic‐euglycaemic clamp 102 . No impact on IMCL and EMCL of tibialis anterior measured by 1 H‐MRS was reported 102 .…”

“…Indeed, SGLT‐2 inhibitors promote FAO by decreasing glucose bioavailability through urinary excretion (Figure 3). Interestingly, EGF was compared to sitagliptin, a dipeptidyl peptidase‐4 inhibitor, at the daily dose of 100 mg/day for 12 weeks also 102 . No changes in body mass index, total adiposity assessed by dual‐energy X‐ray absorptiometry and liver and muscle lipid content assessed by 1 H‐MRS were reported 102 …”