H S Bajaj1, R E Brown2, L Bhullar3, N Sohi4, S Kalra4, R Aronson2. 1. LMC Diabetes and Endocrinology Brampton, 2979, Bovaird Dr. E, L6S0C6 Brampton, Ontario, Canada; Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, 60, Murray street, M5T3L9 Toronto, Ontario, Canada. Electronic address: harpreet.bajaj@lmc.ca. 2. LMC Diabetes and Endocrinology Toronto, 1929, Bayview avenue, M4G3E8 Toronto, Ontario, Canada. 3. LMC Diabetes and Endocrinology Brampton, 2979, Bovaird Dr. E, L6S0C6 Brampton, Ontario, Canada. 4. Royal College of Surgeons, 123, street Stephen's Green, Dublin, Ireland.
Abstract
AIM: The impact of new classes of glucose lowering medications on markers of non-alcoholic fatty liver disease (NAFLD) associated with type 2 diabetes (T2D) have been inconsistent in their magnitude and independence. This large retrospective study investigates changes in alanine aminotransferase (ALT) levels among subjects initiated on newer classes of T2D medications in comparison to a reference control group. METHODS: We studied people with T2D from a large Canadian diabetes register, who had canagliflozin, dapagliflozin, liraglutide, sitagliptin or no further treatment added to their diabetes treatments. Stepwise multiple regression was used to determine the association of A1c and weight change on ALT. Propensity score weighting was used to balance baseline characteristics between treatment groups. RESULTS: A total of 3667 subjects met study criteria. ALT levels (mean follow-up 4.8 months) were lower after treatment with sodium glucose co-transporter 2 (SGLT2) inhibitors, canagliflozin (-4.3U/L, P<0.01) and dapagliflozin (-3.5U/L, P<0.01), compared to incretin agents, liraglutide (-2.1U/L, P<0.01) and sitagliptin (-1.8U/L, P<0.01), each greater than the control group. Only the SGLT2 inhibitor treatment groups maintained a significant ALT reduction vs. control following multivariable adjustment and propensity score weighting. Greater ALT reductions were seen with higher baseline ALT for both the SGLT2 inhibitor treatment groups. CONCLUSION: SGLT2 inhibitors canagliflozin and dapagliflozin resulted in a weight and A1c-independent reduction of ALT levels compared to incretin agents, with a dose-response observed at higher baseline ALT levels. Further studies investigating the differential effects of these drug classes on NAFLD, and insulin/glucagon levels as potential mechanism explaining these differences, should be performed.
AIM: The impact of new classes of glucose lowering medications on markers of non-alcoholic fatty liver disease (NAFLD) associated with type 2 diabetes (T2D) have been inconsistent in their magnitude and independence. This large retrospective study investigates changes in alanine aminotransferase (ALT) levels among subjects initiated on newer classes of T2D medications in comparison to a reference control group. METHODS: We studied people with T2D from a large Canadian diabetes register, who had canagliflozin, dapagliflozin, liraglutide, sitagliptin or no further treatment added to their diabetes treatments. Stepwise multiple regression was used to determine the association of A1c and weight change on ALT. Propensity score weighting was used to balance baseline characteristics between treatment groups. RESULTS: A total of 3667 subjects met study criteria. ALT levels (mean follow-up 4.8 months) were lower after treatment with sodium glucose co-transporter 2 (SGLT2) inhibitors, canagliflozin (-4.3U/L, P<0.01) and dapagliflozin (-3.5U/L, P<0.01), compared to incretin agents, liraglutide (-2.1U/L, P<0.01) and sitagliptin (-1.8U/L, P<0.01), each greater than the control group. Only the SGLT2 inhibitor treatment groups maintained a significant ALT reduction vs. control following multivariable adjustment and propensity score weighting. Greater ALT reductions were seen with higher baseline ALT for both the SGLT2 inhibitor treatment groups. CONCLUSION:SGLT2 inhibitors canagliflozin and dapagliflozin resulted in a weight and A1c-independent reduction of ALT levels compared to incretin agents, with a dose-response observed at higher baseline ALT levels. Further studies investigating the differential effects of these drug classes on NAFLD, and insulin/glucagon levels as potential mechanism explaining these differences, should be performed.
Authors: Giada Sebastiani; Keyur Patel; Vlad Ratziu; Jordan J Feld; Brent A Neuschwander-Tetri; Massimo Pinzani; Salvatore Petta; Annalisa Berzigotti; Peter Metrakos; Naglaa Shoukry; Elizabeth M Brunt; An Tang; Jeremy F Cobbold; Jean-Marie Ekoe; Karen Seto; Peter Ghali; Stéphanie Chevalier; Quentin M Anstee; Heather Watson; Harpreet Bajaj; James Stone; Mark G Swain; Alnoor Ramji Journal: Can Liver J Date: 2022-02-04
Authors: Santo Colosimo; Federico Ravaioli; Maria L Petroni; Lucia Brodosi; Francesca Marchignoli; Francesca A Barbanti; Anna S Sasdelli; Giulio Marchesini; Loris Pironi Journal: Liver Int Date: 2021-02-10 Impact factor: 5.828
Authors: Lars Johansson; Paul D Hockings; Eva Johnsson; Nalina Dronamraju; Jill Maaske; Ricardo Garcia-Sanchez; John P H Wilding Journal: Diabetes Obes Metab Date: 2020-03-09 Impact factor: 6.577
Authors: Alvaro Santos-Laso; María Gutiérrez-Larrañaga; Marta Alonso-Peña; Juan M Medina; Paula Iruzubieta; María Teresa Arias-Loste; Marcos López-Hoyos; Javier Crespo Journal: Biomedicines Date: 2021-12-26