Beneficial effects of SGLT2 inhibitors on fatty liver in type 2 diabetes: A common comorbidity associated with severe complications.

Scheen, André

doi:10.1016/j.diabet.2019.01.008

Article (Scientific journals)

Beneficial effects of SGLT2 inhibitors on fatty liver in type 2 diabetes: A common comorbidity associated with severe complications.

Scheen, André

2019 • In Diabetes & metabolism

Peer reviewed

Permalink
https://hdl.handle.net/2268/235352

DOI
10.1016/j.diabet.2019.01.008

PubMed
30708071

Files (1)Send to Details Statistics Bibliography Similar publications

Files

Full Text

2019 D&M Beneficial effects of SGLT2 inhibitors on fatty liver.pdf

Publisher postprint (632.31 kB)

Request a copy

All documents in ORBi are protected by a user license.

Send to

RIS BibTex APA Chicago Permalink X Linkedin

Details

Keywords :

Fatty liver; Liver enzymes; NAFLD; NASH; SGLT2 inhibitor

Abstract :

[en] Patients with type 2 diabetes mellitus (T2DM) are exposed to non-alcoholic fatty liver disease (NAFLD), a comorbidity associated with cardiovascular disease and chronic kidney disease, and which may progress to non-alcoholic steatohepatitis (NASH), fibrosis and cirrhosis. Sodium-glucose cotransporter type-2 (SGLT2) inhibitors are glucose-lowering agents that improve glucose control while promoting weight loss and lowering serum uric acid levels. These agents may exert cardiovascular and renal protection in T2DM patients with established cardiovascular disease. Recent findings from both randomized controlled trials and open-label studies have also shown that SGLT2 inhibitors are able to reduce fatty liver content, as assessed by different imaging techniques, and improve biological markers of NAFLD, especially serum liver enzymes, in patients with T2DM. In addition, there are emerging data to suggest a mechanism beyond the reduction of hyperglycaemia and body weight, and a potential role for the decrease in low-grade inflammation and oxidative stress associated with SGLT2 inhibitor therapy. This positive effect of SGLT2 inhibitors on NAFLD complements their already well-known effects on cardiovascular and chronic kidney diseases.

Disciplines :

Pharmacy, pharmacology & toxicology

Author, co-author :

Scheen, André ; Université de Liège - ULiège > Département des sciences cliniques > Département des sciences cliniques

Language :

English

Title :

Beneficial effects of SGLT2 inhibitors on fatty liver in type 2 diabetes: A common comorbidity associated with severe complications.

Publication date :

2019

Journal title :

Diabetes & metabolism

ISSN :

1262-3636

eISSN :

1878-1780

Peer reviewed :

Peer reviewed

Commentary :

Available on ORBi :

since 10 May 2019

Statistics

Number of views

64 (1 by ULiège)

Number of downloads

0 (0 by ULiège)

More statistics

Scopus citations^®

107

Scopus citations^®
without self-citations

OpenCitations

Bibliography

Scheen, AJ, Luyckx, FH, Obesity and liver disease. Best Pract Res Clin Endocrinol Metab 16 (2002), 703–716.
European Association for the Study of the Liver, European Association for the Study of Diabetes, European Association for the Study of Obesity. EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol 64 (2016), 1388–1402.
Stefan, N, Haring, HU, Cusi, K, Non-alcoholic fatty liver disease: causes, diagnosis, cardiometabolic consequences, and treatment strategies. Lancet Diabetes Endocrinol, 2018, 10.1016/S2213-8587(18)30154-2 [Epub ahead of print, Aug 30. pii: S2213-8587(18)30154-2].
Younossi, Z, Tacke, F, Arrese, M, Sharma, BC, Mostafa, I, Bugianesi, E, et al. Global perspectives on non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Hepatology, 2018, 10.1002/hep.30251 [Epub ahead of print].
Byrne, CD, Targher, G, NAFLD: a multisystem disease. J Hepatol 62 (2015), S47–S64.
Adams, LA, Anstee, QM, Tilg, H, Targher, G, Non-alcoholic fatty liver disease and its relationship with cardiovascular disease and other extrahepatic diseases. Gut 66 (2017), 1138–1153.
Scheen, AJ, Esser, N, Paquot, N, Antidiabetic agents: Potential anti-inflammatory activity beyond glucose control. Diabetes Metab 41 (2015), 183–194.
Paradies, G, Paradies, V, Ruggiero, FM, Petrosillo, G, Oxidative stress, cardiolipin and mitochondrial dysfunction in non-alcoholic fatty liver disease. World J Gastroenterol 20 (2014), 14205–14218.
Bonnet, F, Scheen, AJ, Effects of SGLT2 inhibitors on systemic and tissue low-grade inflammation: potential contribution for diabetic complications and cardiovascular disease. Diabetes Metab 44 (2018), 457–464.
Yaribeygi, H, Atkin, SL, Butler, AE, Sahebkar, A, Sodium-glucose cotransporter inhibitors and oxidative stress: An update. J Cell Physiol 234 (2019), 3231–3237.
Leoni, S, Tovoli, F, Napoli, L, Serio, I, Ferri, S, Bolondi, L, Current guidelines for the management of non-alcoholic fatty liver disease: a systematic review with comparative analysis. World J Gastroenterol 24 (2018), 3361–3373.
Sumida, Y, Yoneda, M, Current and future pharmacological therapies for NAFLD/NASH. J Gastroenterol 53 (2018), 362–376.
Iogna Prat, L, Tsochatzis, EA, The effect of antidiabetic medications on non-alcoholic fatty liver disease (NAFLD). Hormones (Athens)17 (2018), 219–229.
Tacelli, M, Celsa, C, Magro, B, Giannetti, A, Pennisi, G, Spatola, F, et al. Antidiabetic drugs in NAFLD: the accomplishment of two goals at once?. Pharmaceuticals (Basel), 11, 2018, 10.3390/ph11040121 [pii: E121].
Snyder, HS, Sakaan, SA, March, KL, Siddique, O, Cholankeril, R, Cummings, CD, et al. Non-alcoholic fatty liver disease: a review of anti-diabetic pharmacologic therapies. J Clin Transl Hepatol 6 (2018), 168–174.
Komiya, C, Tsuchiya, K, Shiba, K, Miyachi, Y, Furuke, S, Shimazu, N, et al. Ipragliflozin improves hepatic steatosis in obese mice and liver dysfunction in type 2 diabetic patients irrespective of body weight reduction. PLoS One, 11, 2016, e0151511.
Scheen, AJ, Cardiovascular effects of new oral glucose-lowering agents: DPP-4 and SGLT-2 inhibitors. Circ Res 122 (2018), 1439–1459.
Scheen, AJ, Effects of glucose-lowering agents on renal surrogate endpoints and hard clinical outcomes in patients with type 2 diabetes. Diabetes Metab, 2018, 10.1016/j.diabet.2018.10.003 [Epub ahead of print, pii: S1262-3636(18)30197-6].
Davies, MJ, D'Alessio, DA, Fradkin, J, Kernan, WN, Mathieu, C, Mingrone, G, et al. Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA)and the European Association for the Study of Diabetes (EASD). Diabetologia 61 (2018), 2461–2498.
Ito, D, Shimizu, S, Inoue, K, Saito, D, Yanagisawa, M, Inukai, K, et al. Comparison of ipragliflozin and pioglitazone effects on non-alcoholic fatty liver disease in patients with type 2 diabetes: a randomized, 24-week, open-label, active-controlled trial. Diabetes Care 40 (2017), 1364–1372.
Shibuya, T, Fushimi, N, Kawai, M, Yoshida, Y, Hachiya, H, Ito, S, et al. Luseogliflozin improves liver fat deposition compared to metformin in type 2 diabetes patients with non-alcoholic fatty liver disease: A prospective randomized controlled pilot study. Diabetes Obes Metab 20 (2018), 438–442.
Eriksson, JW, Lundkvist, P, Jansson, PA, Johansson, L, Kvarnstrom, M, Moris, L, et al. Effects of dapagliflozin and n-3 carboxylic acids on non-alcoholic fatty liver disease in people with type 2 diabetes: a double-blind randomised placebo-controlled study. Diabetologia 61 (2018), 1923–1934.
Kuchay, MS, Krishan, S, Mishra, SK, Farooqui, KJ, Singh, MK, Wasir, JS, et al. Effect of empagliflozin on liver fat in patients with type 2 diabetes and non-alcoholic fatty liver disease: a randomized controlled trial (E-LIFT Trial). Diabetes Care 41 (2018), 1801–1808.
Shimizu, M, Suzuki, K, Kato, K, Jojima, T, Iijima, T, Murohisa, T, et al. Evaluation of the effects of dapagliflozin, an SGLT2 inhibitor, on hepatic steatosis and fibrosis by transient elastography in patients with type 2 diabetes and non-alcoholic fatty liver disease. Diabetes Obes Metab 21 (2019), 285–292.
Kusunoki, M, Natsume, Y, Sato, D, Tsutsui, H, Miyata, T, Tsutsumi, K, et al. Luseogliflozin, a sodium glucose co-transporter 2 inhibitor, alleviates hepatic impairment in Japanese patients with type 2 diabetes. Drug Res 66 (2016), 603–606.
Tobita, H, Sato, S, Miyake, T, Ishihara, S, Kinoshita, Y, Effects of dapagliflozin on body composition and liver tests in patients with non-alcoholic steatohepatitis associated with type 2 diabetes mellitus: a prospective, open-label, uncontrolled study. Curr Ther Res Clin Exp 87 (2017), 13–19.
Cefalu, WT, Leiter, LA, Yoon, KH, Arias, P, Niskanen, L, Xie, J, et al. Efficacy and safety of canagliflozin versus glimepiride in patients with type 2 diabetes inadequately controlled with metformin (CANTATA-SU): 52 week results from a randomised, double-blind, phase 3 non-inferiority trial. Lancet 382 (2013), 941–950.
Sattar, N, Fitchett, D, Hantel, S, George, JT, Zinman, B, Empagliflozin is associated with improvements in liver enzymes potentially consistent with reductions in liver fat: results from randomised trials including the EMPA-REG OUTCOME® trial. Diabetologia 61 (2018), 2155–2163.
Leiter, LA, Forst, T, Polidori, D, Balis, DA, Xie, J, Sha, S, Effect of canagliflozin on liver function tests in patients with type 2 diabetes. Diabetes Metab 42 (2016), 25–32.
Castera, L, Diagnosis of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis: Non-invasive tests are enough. Liver Int 38:Suppl 1 (2018), 67–70.
Seko, Y, Sumida, Y, Tanaka, S, Mori, K, Taketani, H, Ishiba, H, et al. Effect of sodium glucose cotransporter 2 inhibitor on liver function tests in Japanese patients with non-alcoholic fatty liver disease and type 2 diabetes mellitus. Hepatol Res 47 (2017), 1072–1078.
Cuthbertson, DJ, Weickert, MO, Lythgoe, D, Sprung, VS, Dobson, R, Shoajee-Moradie, F, et al. External validation of the fatty liver index and lipid accumulation product indices, using 1H-magnetic resonance spectroscopy, to identify hepatic steatosis in healthy controls and obese, insulin-resistant individuals. Eur J Endocrinol 171 (2014), 561–569.
Takase, T, Nakamura, A, Miyoshi, H, Yamamoto, C, Atsumi, T, Amelioration of fatty liver index in patients with type 2 diabetes on ipragliflozin: an association with glucose-lowering effects. Endocr J 64 (2017), 363–367.
Tabuchi, H, Maegawa, H, Tobe, K, Nakamura, I, Uno, S, Effect of ipragliflozin on liver function in Japanese type 2 diabetes mellitus patients: a subgroup analysis of the STELLA-LONG TERM study (3-month interim results). Endocr J 66 (2019), 31–41.
Stasi, C, Milani, S, Non-invasive assessment of liver fibrosis: between prediction/prevention of outcomes and cost-effectiveness. World J Gastroenterol 22 (2016), 1711–1720.
Kurinami, N, Sugiyama, S, Yoshida, A, Hieshima, K, Miyamoto, F, Kajiwara, K, et al. Dapagliflozin significantly reduced liver fat accumulation associated with a decrease in abdominal subcutaneous fat in patients with inadequately controlled type 2 diabetes mellitus. Diabetes Res Clin Pract 142 (2018), 254–263.
Zhang, YN, Fowler, KJ, Hamilton, G, Cui, JY, Sy, EZ, Balanay, M, et al. Liver fat imaging-a clinical overview of ultrasound, CT, and MR imaging. Br J Radiol, 91, 2018 [20170959].
Al Rifai, M, Silverman, MG, Nasir, K, Budoff, MJ, Blankstein, R, Szklo, M, et al. The association of non-alcoholic fatty liver disease, obesity, and metabolic syndrome, with systemic inflammation and subclinical atherosclerosis: the Multi-Ethnic Study of Atherosclerosis (MESA). Atherosclerosis 239 (2015), 629–633.
Roulot, D, Roudot-Thoraval, F, Nkontchou, G, Kouacou, N, Costes, JL, Elourimi, G, et al. Concomitant screening for liver fibrosis and steatosis in French type 2 diabetic patients using Fibroscan. Liver Int 37 (2017), 1897–1906.
Xia, B, Wang, F, Friedrich-Rust, M, Zhou, F, Zhu, J, Yang, H, et al. Feasibility and efficacy of transient elastography using the XL probe to diagnose liver fibrosis and cirrhosis: a meta-analysis. Medicine (Baltimore), 97, 2018, e11816.
Akuta, N, Watanabe, C, Kawamura, Y, Arase, Y, Saitoh, S, Fujiyama, S, et al. Effects of a sodium-glucose cotransporter 2 inhibitor in non-alcoholic fatty liver disease complicated by diabetes mellitus: Preliminary prospective study based on serial liver biopsies. Hepatol Commun 1 (2017), 46–52.
Inoue, M, Hayashi, A, Taguchi, T, Arai, R, Sasaki, S, Takano, K, et al. Effects of canagliflozin on body composition and hepatic fat content in type 2 diabetes patients with non-alcoholic fatty liver disease. J Diabetes Investig, 2018, 10.1111/jdi.12980 [Epub ahead of print].
Sumida, Y, Murotani, K, Saito, M, Tamasawa, A, Osonoi, Y, Yoneda, M, et al. Effect of luseogliflozin on hepatic fat content in type 2 diabetes patients with non-alcoholic fatty liver disease: A prospective, single-arm trial (LEAD trial). Hepatol Res 49 (2019), 64–71.
Li, B, Wang, Y, Ye, Z, Yang, H, Cui, X, Wang, Z, et al. Effects of canagliflozin on fatty liver indexes in patients with type 2 diabetes: a meta-analysis of randomized controlled trials. J Pharm Pharm Sci 21 (2018), 222–235.
Choi, DH, Jung, CH, Mok, JO, Kim, CH, Kang, SK, Kim, BY, Effect of dapagliflozin on alanine aminotransferase improvement in type 2 diabetes mellitus with non-alcoholic fatty liver disease. Endocrinol Metab (Seoul)33 (2018), 387–394.
Itani, T, Ishihara, T., Efficacy of canagliflozin against non-alcoholic fatty liver disease: a prospective cohort study. Obes Sci Pract 4 (2018), 477–482.
Ohta, A, Kato, H, Ishii, S, Sasaki, Y, Nakamura, Y, Nakagawa, T, et al. Ipragliflozin, a sodium glucose co-transporter 2 inhibitor, reduces intrahepatic lipid content and abdominal visceral fat volume in patients with type 2 diabetes. Expert Opin Pharmacother 18 (2017), 1433–1438.
Miyake, T, Yoshida, S, Furukawa, S, Sakai, T, Tada, F, Senba, H, et al. Ipragliflozin ameliorates liver damage in non-alcoholic fatty liver disease. Open Med (Wars)13 (2018), 402–409.
Ohki, T, Isogawa, A, Toda, N, Tagawa, K, Effectiveness of ipragliflozin, a sodium-glucose co-transporter 2 inhibitor, as a second-line treatment for non-alcoholic fatty liver disease patients with type 2 diabetes mellitus who do not respond to incretin-based therapies including glucagon-like peptide-1 analogs and dipeptidyl peptidase-4 inhibitors. Clin Drug Investig 36 (2016), 313–319.
Matsuba, R, Matsuba, I, Shimokawa, M, Nagai, Y, Tanaka, Y, Tofogliflozin decreases body fat mass and improves peripheral insulin resistance. Diabetes Obes Metab 20 (2018), 1311–1315.
Lee, PCH, Gu, Y, Yeung, MY, Fong, CHY, Woo, YC, Chow, WS, et al. Dapagliflozin and empagliflozin ameliorate hepatic dysfunction among Chinese subjects with diabetes in part through glycemic improvement: a single-center, retrospective, observational study. Diabetes Ther 9 (2018), 285–295.
Akuta, N, Kawamura, Y, Watanabe, C, Nishimura, A, Okubo, M, Mori, Y, et al. Impact of SGLT2 inhibitor to histological features and glucose metabolism of non-alcoholic fatty liver disease complicated by diabetes mellitus. Hepatol Res, 2018, 10.1111/hepr.13304 [Epub ahead of print].
Seko, Y, Nishikawa, T, Umemura, A, Yamaguchi, K, Moriguchi, M, Yasui, K, et al. Efficacy and safety of canagliflozin in type 2 diabetes mellitus patients with biopsy-proven non-alcoholic steatohepatitis classified as stage 1-3 fibrosis. Diabetes Metab Syndr Obes 11 (2018), 835–843.
Takeda, A, Irahara, A, Nakano, A, Takata, E, Koketsu, Y, Kimata, K, et al. The improvement of the hepatic histological findings in a patient with non-alcoholic steatohepatitis with type 2 diabetes after the administration of the sodium-glucose cotransporter 2 inhibitor ipragliflozin. Intern Med 56 (2017), 2739–2744.
Radaelli, MG, Martucci, F, Perra, S, Accornero, S, Castoldi, G, Lattuada, G, et al. NAFLD/NASH in patients with type 2 diabetes and related treatment options. J Endocrinol Invest 41 (2018), 509–521.
Scheen, AJ, Cardiovascular outcome studies in type 2 diabetes: comparison between SGLT2 inhibitors and GLP-1 receptor agonists. Diabetes Res Clin Pract 143 (2018), 88–100.
Olubamwo, OO, Virtanen, JK, Voutilainen, A, Kauhanen, J, Pihlajamaki, J, Tuomainen, TP, Association of fatty liver index with the risk of incident cardiovascular disease and acute myocardial infarction. Eur J Gastroenterol Hepatol 30 (2018), 1047–1054.
Mantovani, A, Zaza, G, Byrne, CD, Lonardo, A, Zoppini, G, Bonora, E, et al. Non-alcoholic fatty liver disease increases risk of incident chronic kidney disease: A systematic review and meta-analysis. Metabolism 79 (2018), 64–76.
Rix, I, Steen Pedersen, J, Storgaard, H, Gluud, LL, Cardiometabolic effects of antidiabetic drugs in non-alcoholic fatty liver disease. Clin Physiol Funct Imaging, 2018, 10.1111/cpf.12526 [Epub ahead of print].
Verma, S, McMurray, JJV, SGLT2 inhibitors and mechanisms of cardiovascular benefit: a state-of-the-art review. Diabetologia 61 (2018), 2108–2117.
Heerspink, HJL, Kosiborod, M, Inzucchi, SE, Cherney, DZI, Renoprotective effects of sodium-glucose cotransporter-2 inhibitors. Kidney Int 94 (2018), 26–39.
Scheen, AJ, Effect of sodium-glucose cotransporter type 2 inhibitors on liver fat in patients with type 2 diabetes: hepatic beyond cardiovascular and renal protection?. Ann Transl Med, 6, 2018, S68.
Pafili, K, Maltezos, E, Papanas, N, Ipragliflozin and sodium glucose transporter 2 inhibitors to reduce liver fat: will the prize we sought be won?. Expert Opin Pharmacother 19 (2018), 185–187.
Zelniker, TA, Wiviott, SD, Raz, I, Im, K, Goodrich, EL, Bonaca, MP, et al. SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet 393 (2019), 31–39.
Markham, A, Ertugliflozin: first global approval. Drugs 78 (2018), 513–519.
Sims, H, Smith, KH, Bramlage, P, Minguet, J, Sotagliflozin: a dual sodium-glucose co-transporter-1 and -2 inhibitor for the management of Type 1 and Type 2 diabetes mellitus. Diabet Med 35 (2018), 1037–1048.
Green, CJ, Marjot, T, Tomlinson, JW, Hodson, L, Of mice and men: is there a future for metformin in the treatment of hepatic steatosis?. Diabetes Obes Metab, 2018, 10.1111/dom.13592 [Epub ahead of print].
Ishihara, H, Anai, M, Seino, H, Kitazawa, T, Ohashi, H, Ai, M, et al. Rationale and design of the STOP-OB study for evaluating the effects of tofogliflozin and glimepiride on fat deposition in type 2 diabetes patients treated with metformin/DPP-4 inhibitor dual therapy. Diabetes Ther 9 (2018), 2117–2125.
Itou, M, Kawaguchi, T, Taniguchi, E, Sata, M, Dipeptidyl peptidase-4: a key player in chronic liver disease. World J Gastroenterol 19 (2013), 2298–2306.
Cui, J, Philo, L, Nguyen, P, Hofflich, H, Hernandez, C, Bettencourt, R, et al. Sitagliptin vs. placebo for non-alcoholic fatty liver disease: a randomized controlled trial. J Hepatol 65 (2016), 369–376.
Cusi, K, Orsak, B, Bril, F, Lomonaco, R, Hecht, J, Ortiz-Lopez, C, et al. Long-term pioglitazone treatment for patients with non-alcoholic steatohepatitis and prediabetes or type 2 diabetes mellitus: a randomized trial. Ann Intern Med 165 (2016), 305–315.
Musso, G, Cassader, M, Paschetta, E, Gambino, R, Thiazolidinediones and advanced liver fibrosis in non-alcoholic steatohepatitis: a meta-analysis. JAMA Intern Med 177 (2017), 633–640.
Armstrong, MJ, Houlihan, DD, Rowe, IA, Clausen, WH, Elbrond, B, Gough, SC, et al. Safety and efficacy of liraglutide in patients with type 2 diabetes and elevated liver enzymes: individual patient data meta-analysis of the LEAD program. Aliment Pharmacol Ther 37 (2013), 234–242.
Cusi, K, Sattar, N, Garcia-Perez, LE, Pavo, I, Yu, M, Robertson, KE, et al. Dulaglutide decreases plasma aminotransferases in people with Type 2 diabetes in a pattern consistent with liver fat reduction: a post hoc analysis of the AWARD programme. Diabet Med 35 (2018), 1434–1439.
Dutour, A, Abdesselam, I, Ancel, P, Kober, F, Mrad, G, Darmon, P, et al. Exenatide decreases liver fat content and epicardial adipose tissue in patients with obesity and type 2 diabetes: a prospective randomized clinical trial using magnetic resonance imaging and spectroscopy. Diabetes Obes Metab 18 (2016), 882–891.
Armstrong, MJ, Gaunt, P, Aithal, GP, Barton, D, Hull, D, Parker, R, et al. Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, double-blind, randomised, placebo-controlled phase 2 study. Lancet 387 (2016), 679–690.
Armstrong, MJ, Hull, D, Guo, K, Barton, D, Hazlehurst, JM, Gathercole, LL, et al. Glucagon-like peptide 1 decreases lipotoxicity in non-alcoholic steatohepatitis. J Hepatol 64 (2016), 399–408.
Scheen, AJ, GLP-1 receptor agonists and cardiovascular protection. Class effect or not?. Diabetes Metab 44 (2018), 193–196.
Athyros, VG, Katsiki, N, Karagiannis, A, Editorial: can glucagon like peptide 1 (GLP1)agonists or sodium-glucose co-transporter 2 (SGLT2)inhibitors ameliorate non-alcoholic steatohepatitis in people with or without diabetes?. Curr Vasc Pharmacol 14 (2016), 494–497.
Bajaj, HS, Brown, RE, Bhullar, L, Sohi, N, Kalra, S, Aronson, R, SGLT2 inhibitors and incretin agents: associations with alanine aminotransferase activity in type 2 diabetes. Diabetes Metab 44 (2018), 493–499.
DeFronzo, RA, Combination therapy with GLP-1 receptor agonist and SGLT2 inhibitor. Diabetes Obes Metab 19 (2017), 1353–1362.
DeFronzo, RA, Chilton, R, Norton, L, Clarke, G, Ryder, RE, Abdul-Ghani, M, Revitalization of pioglitazone: the optimal agent to be combined with an SGLT2 inhibitor. Diabetes Obes Metab 18 (2016), 454–462.
Kovacs, CS, Seshiah, V, Merker, L, Christiansen, AV, Roux, F, Salsali, A, et al. Empagliflozin as add-on therapy to pioglitazone with or without metformin in patients with type 2 diabetes mellitus. Clin Ther 37 (2015), 1773–1788.
Frias, JP, Guja, C, Hardy, E, Ahmed, A, Dong, F, Ohman, P, et al. Exenatide once weekly plus dapagliflozin once daily versus exenatide or dapagliflozin alone in patients with type 2 diabetes inadequately controlled with metformin monotherapy (DURATION-8): a 28 week, multicentre, double-blind, phase 3, randomised controlled trial. Lancet Diabetes Endocrinol 4 (2016), 1004–1016.
Ludvik, B, Frias, JP, Tinahones, FJ, Wainstein, J, Jiang, H, Robertson, KE, et al. Dulaglutide as add-on therapy to SGLT2 inhibitors in patients with inadequately controlled type 2 diabetes (AWARD-10): a 24-week, randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol 6 (2018), 370–381.
Seino, Y, Yabe, D, Sasaki, T, Fukatsu, A, Imazeki, H, Ochiai, H, et al. Sodium-glucose cotransporter-2 inhibitor luseogliflozin added to glucagon-like peptide 1 receptor agonist liraglutide improves glycemic control with bodyweight and fat mass reductions in Japanese patients with type 2 diabetes: a 52-week, open-label, single-arm study. J Diabetes Investig 9 (2018), 332–340.
Lee, PC, Ganguly, S, Goh, SY, Weight loss associated with sodium-glucose cotransporter-2 inhibition: a review of evidence and underlying mechanisms. Obes Rev 19 (2018), 1630–1641.
Luyckx, FH, Desaive, C, Thiry, A, Dewe, W, Scheen, AJ, Gielen, JE, et al. Liver abnormalities in severely obese subjects: Effect of drastic weight loss after gastroplasty. Int J Obes 22 (1998), 222–226.
Cai, X, Yang, W, Gao, X, Chen, Y, Zhou, L, Zhang, S, et al. The association between the dosage of SGLT2 inhibitor and weight reduction in type 2 diabetes patients: a meta-analysis. Obesity 26 (2018), 70–80.
Tang, L, Wu, Y, Tian, M, Sjostrom, CD, Johansson, U, Peng, XR, et al. Dapagliflozin slows the progression of the renal and liver fibrosis associated with type 2 diabetes. Am J Physiol Endocrinol Metab 313 (2017), 563–576.
Garvey, WT, Van Gaal, L, Leiter, LA, Vijapurkar, U, List, J, Cuddihy, R, et al. Effects of canagliflozin versus glimepiride on adipokines and inflammatory biomarkers in type 2 diabetes. Metabolism 85 (2018), 32–37.
Polyzos, SA, Kountouras, J, Mantzoros, CS, Adipokines in non-alcoholic fatty liver disease. Metabolism 65 (2016), 1062–1079.
Spiga, R, Marini, MA, Mancuso, E, Di Fatta, C, Fuoco, A, Perticone, F, et al. Uric acid is associated with inflammatory biomarkers and induces inflammation via activating the NF-kappaB signaling pathway in HepG2 cells. Arterioscler Thromb Vasc Biol 37 (2017), 1241–1249.
Wu, AH, Gladden, JD, Ahmed, M, Ahmed, A, Filippatos, G, Relation of serum uric acid to cardiovascular disease. Int J Cardiol 213 (2016), 4–7.
Wang, J, Yu, Y, Li, X, Li, D, Xu, C, Yuan, J, et al. Serum uric acid levels and decreased estimated glomerular filtration rate in patients with type 2 diabetes: a cohort study and meta-analysis. Diabetes Metab Res Rev, 34, 2018, e3046.
Zhou, Y, Wei, F, Fan, Y, High serum uric acid and risk of non-alcoholic fatty liver disease: A systematic review and meta-analysis. Clin Biochem 49 (2016), 636–642.
Darmawan, G, Hamijoyo, L, Hasan, I, Association between serum uric acid and non-alcoholic fatty liver disease: a meta-analysis. Acta Med Indones 49 (2017), 136–147.
Zhao, Y, Xu, L, Tian, D, Xia, P, Zheng, H, Wang, L, et al. Effects of sodium-glucose co-transporter 2 (SGLT2)inhibitors on serum uric acid level: A meta-analysis of randomized controlled trials. Diabetes Obes Metab 20 (2018), 458–462.