Effect of canagliflozin treatment on hepatic triglyceride content and glucose metabolism in patients with type 2 diabetes
Abstract
Aim: To evaluate the impact of the sodium glucose co‐transporter 2 inhibitor canagliflozin on intrahepatic triglyceride (IHTG) accumulation and its relationship to changes in body weight and glucose metabolism. Materials and methods: In this double‐blind, parallel‐group, placebo‐controlled, 24‐week trial subjects with inadequately controlled type 2 diabetes mellitus (T2DM; HbA1c = 7.7% ± 0.7%) from two centres were randomly assigned (1:1) to canagliflozin 300 mg or placebo. We measured IHTG by proton‐magnetic resonance spectroscopy (primary outcome), hepatic/muscle/adipose tissue insulin sensitivity during a 2‐step euglycaemic insulin clamp, and beta‐cell function during a mixed meal tolerance test. Analyses were per protocol. Results: Between 8 September 2014‐13 June 2016, 56 patients were enrolled. Canagliflozin reduced HbA1c (placebo‐subtracted change: −0.71% [−1.08; −0.33]) and body weight (−3.4% [−5.4; −1.4]; both P ≤ 0.001). A numerically larger absolute decrease in IHTG occurred with canagliflozin (−4.6% [−6.4; −2.7]) versus placebo (−2.4% [−4.2; −0.6]; P = 0.09). In patients with non‐alcoholic fatty liver disease (n = 37), the decrease in IHTG was −6.9% (−9.5; −4.2) versus −3.8% (−6.3; −1.3; P = 0.05), and strongly correlated with the magnitude of weight loss (r = 0.69, P < 0.001). Body weight loss ≥5% with a ≥30% relative reduction in IHTG occurred more often with canagliflozin (38% vs. 7%, P = 0.009). Hepatic insulin sensitivity improved with canagliflozin ( P < 0.01), but not muscle or adipose tissue insulin sensitivity. Beta‐cell glucose sensitivity, insulin clearance, and disposition index improved more with canagliflozin ( P < 0.05). Conclusions: Canagliflozin improves hepatic insulin sensitivity and insulin secretion and clearance in patients with T2DM. IHTG decreases in proportion to the magnitude of body weight loss, which tended to be greater and occur more often with canagliflozin.
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The moderate weight loss effects of SGLT2I are explained at least in major parts by drug-elicited increase in glucosuria with consecutive calory loss of about 200 kcal per day.
“which is explainedat least in major parts -by the drug-elicited increase in glucosuria with a consecutive calory loss of about 200 kcal per day [149].”
From Obesity and MASLD: Is weight loss the (only) key to treat metabolic liver disease? (2024) · cites this paper as [149]
Cites
Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes
Zinman, B., Wanner, C., Lachin, J. M., Fitchett, D., Bluhmki, E., Hantel, S., Mattheus, M., Devins, T., Johansen, O. E., Woerle, H. J., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1504720 · Cited by 12,315 · see citing works
Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes
Neal, B., Perkovic, V., Mahaffey, K. W., de Zeeuw, D., Fulcher, G., Erondu, N., Shaw, W., Law, G., Desai, M., & Matthews, D. R. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1611925 · Cited by 7,830 · see citing works
Chalasani, N., Younossi, Z., Lavine, J. E., Charlton, M., Cusi, K., Rinella, M., Harrison, S. A., Brunt, E. M., & Sanyal, A. J. (2018) · Hepatology · doi:10.1002/hep.29367 · Cited by 7,239 · see citing works
Self-citationVilar-Gomez, E., Martinez-Perez, Y., Calzadilla-Bertot, L., Torres-Gonzalez, A., Gra-Oramas, B., Gonzalez-Fabian, L., Friedman, S. L., Diago, M., & Romero-Gomez, M. (2015) · Gastroenterology · doi:10.1053/j.gastro.2015.04.005 · Cited by 2,492 · see citing works
Armstrong, M. J., Gaunt, P., Aithal, G. P., Barton, D., Hull, D., Parker, R., Hazlehurst, J. M., Guo, K., Abouda, G., Aldersley, M. A., et al. (2016) · The Lancet · doi:10.1016/s0140-6736(15)00803-x · Cited by 2,203 · see citing works
A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis
Belfort, R., Harrison, S. A., Brown, K., Darland, C., Finch, J., Hardies, J., Balas, B., Gastaldelli, A., Tio, F., Pulcini, J., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa060326 · Cited by 1,827 · see citing works
Self-citationCusi, K., Orsak, B., Bril, F., Lomonaco, R., Hecht, J., Ortiz-Lopez, C., Tio, F., Hardies, J., Darland, C., Musi, N., et al. (2016) · Annals of Internal Medicine · doi:10.7326/m15-1774 · Cited by 1,024 · see citing works
Self-citationCauter, E. V., Mestrez, F., Sturis, J., & Polonsky, K. (1992) · Diabetes · doi:10.2337/diab.41.3.368 · Cited by 938 · see citing works
Magkos, F., Fraterrigo, G., Yoshino, J., Luecking, C., Kirbach, K., Kelly, S. C., de las Fuentes, L., He, S., Okunade, A. L., Patterson, B. W., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.02.005 · Cited by 886 · see citing works
Bolinder, J., Ljunggren, Ö., Kullberg, J., Johansson, L., Wilding, J., Langkilde, A. M., Sugg, J., & Parikh, S. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-2260 · Cited by 867 · see citing works
Bergman, R. N., Prager, R., Volund, A., & Olefsky, J. M. (1987) · Journal of Clinical Investigation · doi:10.1172/jci112886 · Cited by 772 · see citing works
Kuchay, M. S., Krishan, S., Mishra, S. K., Farooqui, K. J., Singh, M. K., Wasir, J. S., Bansal, B., Kaur, P., Jevalikar, G., Gill, H. K., et al. (2018) · Diabetes Care · doi:10.2337/dc18-0165 · Cited by 662 · see citing works
Renal, metabolic and cardiovascular considerations of SGLT2 inhibition
DeFronzo, R. A., Norton, L., & Abdul‐Ghani, M. A. (2016) · Nature Reviews Nephrology · doi:10.1038/nrneph.2016.170 · Cited by 556 · see citing works
Portillo-Sanchez, P., Bril, F., Maximos, M., Lomonaco, R., Biernacki, D., Orsak, B., Subbarayan, S., Webb, A., Hecht, J., & Cusi, K. (2015) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-1966 · Cited by 503 · see citing works
Self-citationLazo, M., Solga, S. F., Horska, A., Bonekamp, S., Diehl, A. M., Brancati, F. L., Wagenknecht, L. E., Pi-Sunyer, F. X., Kahn, S. E., Clark, J. M., et al. (2010) · Diabetes Care · doi:10.2337/dc10-0856 · Cited by 367 · see citing works
Management of nonalcoholic fatty liver disease in patients with type 2 diabetes: a call to action
Bril, F., & Cusi, K. (2017) · Diabetes Care · doi:10.2337/dc16-1787 · Cited by 341 · see citing works
Self-citationIto, D., Shimizu, S., Inoue, K., Saito, D., Yanagisawa, M., Inukai, K., Akiyama, Y., Morimoto, Y., Noda, M., & Shimada, A. (2017) · Diabetes Care · doi:10.2337/dc17-0518 · Cited by 280 · see citing works
Ortiz‐Lopez, C., Lomonaco, R., Orsak, B., Finch, J., Chang, Z., Kochunov, V., Hardies, J., & Cusi, K. J. (2012) · Diabetes Care · doi:10.2337/dc11-1849 · Cited by 253 · see citing works
Self-citationKomiya, C., Tsuchiya, K., Shiba, K., Miyachi, Y., Furuke, S., Shimazu, N., Yamaguchi, S., Kanno, K., & Ogawa, Y. (2016) · PLoS ONE · doi:10.1371/journal.pone.0151511 · Cited by 230 · see citing works
Sodium–Glucose Cotransporter Inhibitors: Effects on Renal and Intestinal Glucose Transport
Mudaliar, S., Polidori, D., Zambrowicz, B., & Henry, R. R. (2015) · Diabetes Care · doi:10.2337/dc15-0642 · Cited by 225 · see citing works
Self-citationJojima, T., Tomotsune, T., Iijima, T., Akimoto, K., Suzuki, K., & Aso, Y. (2016) · Diabetology & Metabolic Syndrome · doi:10.1186/s13098-016-0169-x · Cited by 202 · see citing works
Yokono, M., Takasu, T., Hayashizaki, Y., Mitsuoka, K., Kihara, R., Muramatsu, Y., Miyoshi, S., Tahara, A., Kurosaki, E., Li, Q., et al. (2014) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2014.01.040 · Cited by 195 · see citing works
Shibuya, T., Fushimi, N., Kawai, M., Yoshida, Y., Hachiya, H., Ito, S., Kawai, H., Ohashi, N., & Mori, A. (2017) · Diabetes Obesity and Metabolism · doi:10.1111/dom.13061 · Cited by 192 · see citing works
Bril, F., Lomonaco, R., Orsak, B., Ortiz‐Lopez, C., Webb, A., Tio, F. O., Hecht, J., & Cusi, K. J. (2013) · Hepatology · doi:10.1002/hep.26988 · Cited by 173 · see citing works
Self-citationNonalcoholic Fatty Liver Disease
Bril, F., & Cusi, K. J. (2016) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2016.06.005 · Cited by 153 · see citing works
Self-citationMetabolic Impact of Nonalcoholic Steatohepatitis in Obese Patients With Type 2 Diabetes
Lomonaco, R., Bril, F., Portillo-Sánchez, P., Ortiz‐Lopez, C., Orsak, B., Biernacki, D., Lo, M. C., Suman, A., Weber, M. H., & Cusi, K. J. (2016) · Diabetes Care · doi:10.2337/dc15-1876 · Cited by 150 · see citing works
Self-citationCefalu, W. T., Buse, J. B., Tuomilehto, J. O., Fleming, G. A., Ferrannini, E., Gerstein, H. C., Bennett, P. H., Ramachandran, A., Raz, I., Rosenstock, J., et al. (2016) · Diabetes Care · doi:10.2337/dc16-0873 · Cited by 143 · see citing works
Tobita, H., Sato, S., Miyake, T., Ishihara, S., & Kinoshita, Y. (2017) · Current Therapeutic Research · doi:10.1016/j.curtheres.2017.07.002 · Cited by 141 · see citing works
Effect of canagliflozin on liver function tests in patients with type 2 diabetes
Leiter, L. A., Forst, T. M., Polidori, D., Balis, D. A., Xie, J., & Sha, S. (2015) · Diabetes & Metabolism · doi:10.1016/j.diabet.2015.10.003 · Cited by 127 · see citing works
Self-citationQiang, S., Nakatsu, Y., Seno, Y., Fujishiro, M., Sakoda, H., Kushiyama, A., Mori, K., Matsunaga, Y., Yamamotoya, T., Kamata, H., et al. (2015) · Diabetology & Metabolic Syndrome · doi:10.1186/s13098-015-0102-8 · Cited by 113 · see citing works
Hayashizaki, Y., Kurosaki, E., Takasu, T., Mitori, H., Yamazaki, S., Koide, K., & Takakura, S. (2015) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2015.02.009 · Cited by 108 · see citing works
Suzuki, M., Takeda, M., Kito, A., Fukazawa, M., Yata, T., Yamamoto, M., Nagata, T., Fukuzawa, T., Yamane, M., Honda, K., et al. (2014) · Nutrition and Diabetes · doi:10.1038/nutd.2014.20 · Cited by 97 · see citing works
Wang, D., Luo, Y., Wang, X., Orlicky, D. J., Myakala, K., Yang, P., & Levi, M. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19010137 · Cited by 95 · see citing works
Remogliflozin Etabonate Improves Fatty Liver Disease in Diet-Induced Obese Male Mice
Nakano, S., Katsuno, K., Isaji, M., Nagasawa, T., Buehrer, B. M., Walker, S., Wilkison, W. O., & Cheatham, B. (2015) · Journal of Clinical and Experimental Hepatology · doi:10.1016/j.jceh.2015.02.005 · Cited by 82 · see citing works
Seko, Y., Sumida, Y., Sasaki, K., Itoh, Y., Iijima, H., Hashimoto, T., Ishii, S., & Inagaki, N. (2017) · Journal of Gastroenterology · doi:10.1007/s00535-017-1364-8 · Cited by 70 · see citing works
Ohta, A., Kato, H., Ishii, S., Sasaki, Y., Nakamura, Y., Nakagawa, T., Nagai, Y., & Tanaka, Y. (2017) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2017.1363888 · Cited by 56 · see citing works
Nishimura, N., Kitade, M., Noguchi, R., Namisaki, T., Moriya, K., Takeda, K., Okura, Y., Aihara, Y., Douhara, A., Kawaratani, H., et al. (2016) · Journal of Gastroenterology · doi:10.1007/s00535-016-1200-6 · Cited by 44 · see citing works
Cusi, K. J., Sanyal, A. J., Zhang, S., Hoogwerf, B. J., Chang, A. M., Jacober, S. J., Bue-Valleskey, J. M., Higdon, A. N., Bastyr, E. J., Haupt, A., et al. (2016) · Diabetes Obesity and Metabolism · doi:10.1111/dom.12751 · Cited by 40 · see citing works
Self-citationHachey, D. L., Parsons, W. R., McKay, S. V., & Haymond, M. W. (1999) · Analytical Chemistry · doi:10.1021/ac990724x · Cited by 35 · see citing works
Portillo-Sánchez, P., Yavuz, S., Bril, F., & Cusi, K. J. (2014) · Current Hepatology Reports · doi:10.1007/s11901-014-0229-3 · Cited by 25 · see citing works
Self-citationKusunoki, M., Natsume, Y., Sato, D., Tsutsui, H., Miyata, T., Tsutsumi, K., Suga, T., & Oshida, Y. (2016) · Drug Research · doi:10.1055/s-0042-111515 · Cited by 19 · see citing works
Flagged first, then by citations
1 of the 42 references couldn’t be matched to a known paper.
Cited by
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Rinella, M. E., Neuschwander-Tetri, B. A., Siddiqui, M. S., Abdelmalek, M. F., Caldwell, S., Barb, D., Kleiner, D. E., & Loomba, R. (2023) · Hepatology · doi:10.1097/hep.0000000000000323 · Cited by 2,667 · see citing works
Self-citationCusi, K., Isaacs, S., Barb, D., Basu, R., Caprio, S., Garvey, W. T., Kashyap, S., Mechanick, J. I., Mouzaki, M., Nadolsky, K., et al. (2022) · Endocrine Practice · doi:10.1016/j.eprac.2022.03.010 · Cited by 1,021 · see citing works
Self-citationThe complex link between NAFLD and type 2 diabetes mellitus - mechanisms and treatments
Targher, G., Corey, K. E., Byrne, C. D., & Roden, M. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-021-00448-y · Cited by 850 · see citing works
Eslam, M., Sarin, S. K., Wong, V. W., Fan, J.-G., Kawaguchi, T., Ahn, S. H., Zheng, M., Shiha, G. E.-S., Yilmaz, Y. N., Gani, R. A., et al. (2020) · Hepatology International · doi:10.1007/s12072-020-10094-2 · Cited by 837 · see citing works
Metabolic dysfunction-associated steatotic liver disease (MASLD): a state-of-the-art review
Chan, W.-K., Chuah, K.-H., Rajaram, R. B., Lim, L.-L., Ratnasingam, J., & Vethakkan, S. R. (2023) · Journal of Obesity & Metabolic Syndrome · doi:10.7570/jomes23052 · Cited by 776 · see citing works
Kanwal, F., Shubrook, J. H., Adams, L. A., Pfotenhauer, K., Wai-Sun Wong, V., Wright, E., Abdelmalek, M. F., Harrison, S. A., Loomba, R., Mantzoros, C. S., et al. (2021) · Gastroenterology · doi:10.1053/j.gastro.2021.07.049 · Cited by 618 · see citing works
Self-citationEmerging therapeutic approaches for the treatment of NAFLD and type 2 diabetes mellitus
Ferguson, D., & Finck, B. N. (2021) · Nature Reviews Endocrinology · doi:10.1038/s41574-021-00507-z · Cited by 507 · see citing works
From NASH to diabetes and from diabetes to NASH: Mechanisms and treatment options
Gastaldelli, A., & Cusi, K. (2019) · JHEP Reports · doi:10.1016/j.jhepr.2019.07.002 · Cited by 455 · see citing works
Self-citationKahl, S., Gancheva, S., Straßburger, K., Herder, C., Machann, J., Katsuyama, H., Kabisch, S., Henkel, E., Kopf, S., Lagerpusch, M., et al. (2020) · Diabetes Care · doi:10.2337/dc19-0641 · Cited by 360 · see citing works
Nonalcoholic fatty liver disease (NAFLD) from pathogenesis to treatment concepts in humans
Pafili, K., & Roden, M. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2020.101122 · Cited by 330 · see citing works
Insulin resistance and insulin sensitizing agents
Mastrototaro, L., & Roden, M. (2021) · Metabolism · doi:10.1016/j.metabol.2021.154892 · Cited by 259 · see citing works
The Relationship Between Type 2 Diabetes, NAFLD, and Cardiovascular Risk
Caussy, C., Aubin, A., & Loomba, R. S. (2021) · Current Diabetes Reports · doi:10.1007/s11892-021-01383-7 · Cited by 246 · see citing works
Nonalcoholic fatty liver disease in adults: current concepts in etiology, outcomes, and management
Marjot, T., Moolla, A., Cobbold, J. F., Hodson, L., & Tomlinson, J. W. (2020) · Endocrine Reviews · doi:10.1210/endrev/bnz009 · Cited by 228 · see citing works
ElSayed, N. A., Aleppo, G., Aroda, V. R., Bannuru, R. R., Brown, F. M., Bruemmer, D., Collins, B. S., Cusi, K. J., Hilliard, M. E., Isaacs, D. M., et al. (2022) · Diabetes Care · doi:10.2337/dc23-s004 · Cited by 233 · see citing works
Self-citationMantovani, A., Byrne, C. D., & Targher, G. (2022) · The Lancet Gastroenterology & Hepatology · doi:10.1016/s2468-1253(21)00261-2 · Cited by 230 · see citing works
ElSayed, N. A., McCoy, R. G., Aleppo, G., Bajaj, M. S., Balapattabi, K., Beverly, E. A., Early, K. B., Bruemmer, D., Cusi, K. J., Echouffo-Tcheugui, J. B., et al. (2024) · Diabetes Care · doi:10.2337/dc25-s004 · Cited by 222 · see citing works
Self-citationNegi, C. K., Babica, P., Bajard, L., Vašků, J. B., & Tarantino, G. (2021) · Metabolism · doi:10.1016/j.metabol.2021.154925 · Cited by 193 · see citing works
Management of non-alcoholic fatty liver disease
Petroni, M. L., Brodosi, L., Bugianesi, E., & Marchesini, G. (2021) · BMJ · doi:10.1136/bmj.m4747 · Cited by 181 · see citing works
Chew, N., Mehta, A., Goh, R. S. J., Zhang, A. A. Y., Chen, Y., Chong, B., Chew, H. S. J., Shabbir, A., Brown, A. C., Dimitriadis, G. K., et al. (2024) · Circulation · doi:10.1161/circulationaha.124.070535 · Cited by 185 · see citing works
Eslam, M., Fan, J., Yu, M., Wong, V. W., Cua, I. H., Liu, C., Tanwandee, T., Gani, R. A., Seto, W., Alam, S., et al. (2025) · Hepatology International · doi:10.1007/s12072-024-10774-3 · Cited by 186 · see citing works
NAFLD, and cardiovascular and cardiac diseases: Factors influencing risk, prediction and treatment
Targher, G., Corey, K. E., & Byrne, C. D. (2020) · Diabetes & Metabolism · doi:10.1016/j.diabet.2020.101215 · Cited by 170 · see citing works
Obesity and MASLD: Is weight loss the (only) key to treat metabolic liver disease?
Huttasch, M., Roden, M., & Kahl, S. (2024) · Metabolism · doi:10.1016/j.metabol.2024.155937 · Cited by 169 · see citing works
Metabolic liver disease in diabetes – From mechanisms to clinical trials
Dewidar, B., KAHL, S., Pafili, K., & Roden, M. (2020) · Metabolism · doi:10.1016/j.metabol.2020.154299 · Cited by 160 · see citing works
Ipragliflozin improves the hepatic outcomes of patients with diabetes with NAFLD
Takahashi, H., Kessoku, T., Kawanaka, M., Nonaka, M., Hyogo, H., Fujii, H., Nakajima, T., Imajo, K., Tanaka, K., Kubotsu, Y., et al. (2022) · Hepatology Communications · doi:10.1002/hep4.1696 · Cited by 153 · see citing works
ElSayed, N. A., Aleppo, G., Bannuru, R. R., Bruemmer, D., Collins, B. S., Cusi, K. J., Ekhlaspour, L., Fleming, T. K., Hilliard, M. E., Johnson, E. L., et al. (2023) · Diabetes Care · doi:10.2337/dc24-s004 · Cited by 167 · see citing works
Self-citationArab, J. P., Dirchwolf, M., Álvares‐da‐Silva, M. R., Francisco Barrera, M., Benítez, C., Castellanos, M., Castro‐Narro, G., Chávez-Tapia, N. C., Chiodi, D., Cotrim, H. P., et al. (2020) · Annals of Hepatology · doi:10.1016/j.aohep.2020.09.006 · Cited by 142 · see citing works
Self-citationMantovani, A., Byrne, C. D., Scorletti, E., Mantzoros, C. S., & Targher, G. (2020) · Diabetes & Metabolism · doi:10.1016/j.diabet.2019.12.007 · Cited by 138 · see citing works
Current and emerging pharmacological options for the treatment of nonalcoholic steatohepatitis
Pοlyzos, S. A., Kang, E. S., Boutari, C., Rhee, E., & Mantzoros, C. S. (2020) · Metabolism · doi:10.1016/j.metabol.2020.154203 · Cited by 139 · see citing works
Mantovani, A., Petracca, G., Csermely, A., Beatrice, G., & Targher, G. (2020) · Metabolites · doi:10.3390/metabo11010022 · Cited by 136 · see citing works
Takeshita, Y., Honda, M., Harada, K., Kita, Y., Takata, N., Tsujiguchi, H., Tanaka, T., Goto, H., Nakano, Y., Iida, N., et al. (2022) · Diabetes Care · doi:10.2337/dc21-2049 · Cited by 130 · see citing works
Byrne, C. D., & Targher, G. (2021) · Diabetes Obesity and Metabolism · doi:10.1111/dom.14484 · Cited by 122 · see citing works
Kullmann, S., Hummel, J., Wagner, R. J., Dannecker, C., Vosseler, A., Fritsche, L., Veit, R., Kantartzis, K., Machann, J., Birkenfeld, A. L., et al. (2021) · Diabetes Care · doi:10.2337/dc21-1136 · Cited by 112 · see citing works
Ranjbar, G., Mikhailidis, D. P., & Sahebkar, A. (2019) · Metabolism · doi:10.1016/j.metabol.2019.154001 · Cited by 108 · see citing works
Roeb, E., Canbay, A. E., Tacke, F., Bantel, H., Bojunga, J., de Laffolie, J., Demir, M., Denzer, U. W., Geier, A., Hofmann, W. P., et al. (2022) · Zeitschrift für Gastroenterologie · doi:10.1055/a-1880-2283 · Cited by 102 · see citing works
Yoneda, M., Honda, Y., Ogawa, Y., Kessoku, T., Kobayashi, T., Imajo, K., Ozaki, A., Nogami, A., Taguri, M., Yamanaka, T., et al. (2021) · BMJ Open Diabetes Research & Care · doi:10.1136/bmjdrc-2020-001990 · Cited by 100 · see citing works
Barb, D., Kalavalapalli, S., Leiva, E. G., Bril, F., Huot-Marchand, P., Dzen, L., Rosenberg, J. T., Junien, J., Broqua, P., Rocha, A. O., et al. (2025) · Journal of Hepatology · doi:10.1016/j.jhep.2024.12.045 · Cited by 91 · see citing works
Self-citationManagement of NAFLD in primary care settings
Wong, V. W., Zelber‐Sagi, S., Cusi, K. J., Carrieri, P., Wright, E. E., Crespo, J., & Lazarus, J. V. (2022) · Liver International · doi:10.1111/liv.15404 · Cited by 82 · see citing works
Self-citationRossing, P. R., Inzucchi, S. E., Vart, P., Jongs, N., Docherty, K. F., Jhund, P. S., Køber, L., Kosiborod, M. N., Martinez, F. A., Ponikowski, P. P., et al. (2021) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(21)00295-3 · Cited by 77 · see citing works
Moon, J. S., Hong, J. H., Jung, Y. J., Ferrannini, E., Nauck, M. A., & Lim, S. K. (2022) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2022.03.005 · Cited by 75 · see citing works
Lee, B., Lee, Y., Park, C., Rhee, E., Lee, W., Kim, N. H., Choi, K. M., Park, K., Choi, Y., Soo, B., et al. (2020) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2020.0010 · Cited by 77 · see citing works
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Cusi, K. J. (2020) · Diabetes Care · doi:10.2337/dci19-0064 · Cited by 69 · see citing works
Self-citationBeneficial effect of anti-diabetic drugs for nonalcoholic fatty liver disease
Kim, K., & Lee, B. (2020) · Clinical and Molecular Hepatology · doi:10.3350/cmh.2020.0137 · Cited by 68 · see citing works
Bajaj, M. S., McCoy, R. G., Balapattabi, K., Bannuru, R. R., Bellini, N. J., Bennett, A. K., Beverly, E. A., Early, K. B., ChallaSivaKanaka, S., Echouffo-Tcheugui, J. B., et al. (2025) · Diabetes Care · doi:10.2337/dc26-s004 · Cited by 86 · see citing works
Gut-pancreas-liver Axis as a target for treatment of NAFLD/NASH
Svegliati-Baroni, G., Patrício, B., Lioci, G., Macedo, M. P., & Gastaldelli, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21165820 · Cited by 66 · see citing works
SGLT2 Inhibition for Cardiovascular Diseases, Chronic Kidney Disease, and NAFLD
Ala, M. (2021) · Endocrinology · doi:10.1210/endocr/bqab157 · Cited by 71 · see citing works
den Kamp, Y. J. M. O., de Ligt, M., Dautzenberg, B., Moonen‐Kornips, E., ESTERLINE, R. L., Hesselink, M. K. C., Joris Hoeks, J., Schrauwen‐Hinderling, V. B., Havekes, B., Oscarsson, J., et al. (2021) · Diabetes Care · doi:10.2337/dc20-2887 · Cited by 63 · see citing works
Coelho, F. D. S., Borges‐Canha, M., von Hafe, M., Neves, J. S., Vale, C., Leite, A. R., Carvalho, D., & Leite‐Moreira, A. (2021) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.3413 · Cited by 61 · see citing works
Role of Agents for the Treatment of Diabetes in the Management of Nonalcoholic Fatty Liver Disease
Budd, J. T., & Cusi, K. J. (2020) · Current Diabetes Reports · doi:10.1007/s11892-020-01349-1 · Cited by 61 · see citing works
Self-citationMichalopoulou, E., Thymis, J., Lampsas, S., Pavlidis, G., Katogiannis, K., Vlachomitros, D., Katsanaki, E., Kostelli, G., Pililis, S., Pliouta, L., et al. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14020428 · Cited by 63 · see citing works
Lee, M. M. Y., Petrie, M. C., McMurray, J. J. V., & Sattar, N. A. (2020) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.119.311904 · Cited by 56 · see citing works
Diabetes as a risk factor for MASH progression
Gancheva, S., Roden, M., & Castéra, L. (2024) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2024.111846 · Cited by 59 · see citing works
Cheung, K. S., Ng, H. Y., Hui, R. W. H., Lam, L. K., Mak, L., Ho, Y. C., Tan, J. T., Chan, E. W., Seto, W., Yuen, M., et al. (2024) · Hepatology · doi:10.1097/hep.0000000000000855 · Cited by 56 · see citing works
Gries, J. J., Lazarus, J. V., Brennan, P., Siddiqui, M. S., Targher, G., Lang, C. C., Virani, S. S., Lavie, C. J., Isaacs, S. D., Arab, J. P., et al. (2024) · The Lancet. Gastroenterology & hepatology · doi:10.1016/s2468-1253(24)00310-8 · Cited by 55 · see citing works
Self-citationCusi, K. J. (2019) · Hepatology · doi:10.1002/hep.30670 · Cited by 52 · see citing works
Self-citationMetabolic syndrome and its association with nonalcoholic steatohepatitis
Bril, F., Sanyal, A., & Cusi, K. (2023) · Clinics in Liver Disease · doi:10.1016/j.cld.2023.01.002 · Cited by 52 · see citing works
Self-citationCariou, B. (2022) · Diabetes Obesity and Metabolism · doi:10.1111/dom.14651 · Cited by 52 · see citing works
Cusi, K. J. (2020) · Liver International · doi:10.1111/liv.14350 · Cited by 52 · see citing works
Self-citationKaneto, H., Obata, A., Kimura, T., Shimoda, M., Kinoshita, T., Matsuoka, T., & Kaku, K. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22063062 · Cited by 48 · see citing works
SGLT2 Inhibitors in Liver Patients
Hsiang, J. C., & Wong, V. W.-S. (2020) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2020.05.021 · Cited by 48 · see citing works
Mori, Y., Duru, O. K., Tuttle, K. R., Fukuma, S., Taura, D., Harada, N., Inagaki, N., & Inoue, K. (2022) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgac591 · Cited by 47 · see citing works
Anti-obesity Medications for the Management of Nonalcoholic Fatty Liver Disease
Pοlyzos, S. A., Goulis, D. G., Γιουλεμέ, Ό., Germanidis, G. S., & Goulas, A. (2022) · Current Obesity Reports · doi:10.1007/s13679-022-00474-0 · Cited by 46 · see citing works
Antifibrotic therapies for metabolic dysfunction-associated steatotic liver disease
Schwabe, R. F., Tacke, F., Sugimoto, A., & Friedman, S. L. (2025) · JHEP Reports · doi:10.1016/j.jhepr.2025.101421 · Cited by 50 · see citing works
Liver-targeting drugs and their effect on blood glucose and hepatic lipids
Gastaldelli, A., Stefan, N., & Häring, H. (2021) · Diabetologia · doi:10.1007/s00125-021-05442-2 · Cited by 46 · see citing works
Colosimo, S., Ravaioli, F., Petroni, M. L., Brodosi, L., Marchignoli, F., Barbanti, F. A., Sasdelli, A. S., Marchesini, G., & Pironi, L. (2021) · Liver International · doi:10.1111/liv.14799 · Cited by 47 · see citing works
Bica, I.-C., Stoica, R. A., Salmen, T., Janež, A., Volčanšek, Š., Popovic, D. S., Muzurović, E. M., Rizzo, M., & Stoian, A. P. (2023) · Medicina · doi:10.3390/medicina59061136 · Cited by 42 · see citing works
NIRANJAN, S., Phillips, B. E., & Giannoukakis, N. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1193373 · Cited by 43 · see citing works
Rossing, P. R., Inzucchi, S. E., Vart, P., Jongs, N., Docherty, K. F., Jhund, P. S., Køber, L., Kosiborod, M., Martínez, F. A., Ponikowski, P. P., et al. (2022) · UCL Discovery (University College London) · Cited by 40 · see citing works
Yoneda, M., Kobayashi, T., Honda, Y., Ogawa, Y., Kessoku, T., Imajo, K., Nogami, A., Taguri, M., Kirikoshi, H., Saito, S., et al. (2022) · Hepatology Communications · doi:10.1002/hep4.1993 · Cited by 39 · see citing works
Comorbidity of patients with noncommunicable diseases in general practice. Eurasian guidelines
Drapkina, O. M., Васильевна, К. А., Калинина, А. М., Avdeev, S. N., Викторович, А. М., Алексеева, Л. И., Almazova, I. I., Andreenko, Е. Y., Antipushina, D. N., Balanova, Y. А., et al. (2024) · CARDIOVASCULAR THERAPY AND PREVENTION · doi:10.15829/1728-8800-2024-3996 · Cited by 49 · see citing works
Zisis, M., Chondrogianni, M. E., Ανδρουτσάκος, Θ., Rantos, I., Oikonomou, E. K., Chatzigeorgiou, A., & Kassi, E. N. (2025) · Biomolecules · doi:10.3390/biom15030324 · Cited by 42 · see citing works
Borisov, A. N., Kutz, A., Christ, E., Heim, M. H., & Ebrahimi, F. (2023) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgad249 · Cited by 37 · see citing works
Impact of NAFLD and its pharmacotherapy on lipid profile and CVD
Wang, Z., Ye, M., Zhang, X., Zhang, P., Cai, J., Li, H., & She, Z. (2022) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2022.07.010 · Cited by 37 · see citing works
Katsiki, N., Perakakis, N., & Mantzoros, C. S. (2019) · Metabolism · doi:10.1016/j.metabol.2019.07.009 · Cited by 36 · see citing works
Marchesini, G., Bugianesi, E., Burra, P., Marra, F., Miele, L., Alisi, A., Vajro, P., Masarone, M., Petta, S., Persico, M., et al. (2021) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2021.04.028 · Cited by 35 · see citing works
Marchesini, G., Bugianesi, E., Burra, P., Marra, F., Miele, L., Alisi, A., Vajro, P., Masarone, M., Petta, S., Persico, M., et al. (2021) · Digestive and Liver Disease · doi:10.1016/j.dld.2021.04.029 · Cited by 33 · see citing works
Empagliflozin Reduces Liver Fat in Individuals With and Without Diabetes
Abdelgani, S., Khattab, A., Adams, J. M., Baskoy, G., Brown, M., Clarke, G., Larvenenko, O., DeFronzo, R. A., & Abdul‐Ghani, M. A. (2024) · Diabetes Care · doi:10.2337/dc23-1646 · Cited by 37 · see citing works
McLean, P., Bennett, J., Woods, E. A., Chandrasekhar, S. A., Newman, N. A., Mohammad, Y., Khawaja, M., Rizwan, A. M., Siddiqui, R., Birnbaum, Y., et al. (2025) · npj Metabolic Health and Disease · doi:10.1038/s44324-025-00068-z · Cited by 34 · see citing works
Clinical implications, diagnosis, and management of diabetes in patients with chronic liver diseases
Chung, W., Promrat, K., & Wands, J. R. (2020) · World Journal of Hepatology · doi:10.4254/wjh.v12.i9.533 · Cited by 33 · see citing works
Management of Diabetes in Candidates for Liver Transplantation and in Transplant Recipients
Brodosi, L., Petta, S., Petroni, M. L., Marchesini, G., & Morelli, M. C. (2021) · Transplantation · doi:10.1097/tp.0000000000003867 · Cited by 34 · see citing works
Hu, Y., Sun, C., Chen, Y., Liu, Y., & Fan, J. (2024) · Journal of Clinical and Translational Hepatology · doi:10.14218/jcth.2024.00123 · Cited by 32 · see citing works
Sodium-glucose co-transporter 2 inhibitors in nonalcoholic fatty liver disease
Makri, E. S., Goulas, A., & Pοlyzos, S. A. (2021) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2021.174272 · Cited by 31 · see citing works
Authors, & Collaborators: (2022) · Zeitschrift für Gastroenterologie · doi:10.1055/a-1880-2388 · Cited by 30 · see citing works
Metabolic reprogramming of immune cells in MASH
Ma, C., Wang, S., Dong, B., & Tian, Y. (2025) · Hepatology · doi:10.1097/hep.0000000000001371 · Cited by 32 · see citing works
Kanwal, F., Bril, F., Wong, V. W., Adams, L. A., Pfotenhauer, K. M., SKOLNIK, N., Wright, E. E., Eckel, R. H., Noureddin, M., Loomba, R. S., et al. (2026) · Gastroenterology · doi:10.1053/j.gastro.2026.01.047 · Cited by 35 · see citing works
Self-citationUpdates in Metabolic Dysfunction‐Associated Fatty Liver Disease (MAFLD) in Children
Rupasinghe, K., Hind, J. M., & Hegarty, R. (2023) · Journal of Pediatric Gastroenterology and Nutrition · doi:10.1097/mpg.0000000000003919 · Cited by 27 · see citing works
Kaylan, K. B., & Paul, S. (2024) · Current Diabetes Reports · doi:10.1007/s11892-024-01558-y · Cited by 27 · see citing works
Konings, L. A. M., Matute, L. M., Boeren, A. M. P., van de Luitgaarden, I. A. T., Dirksmeier-Harinck, F., de Knegt, R. J., Tushuizen, M. E., Grobbee, D. E., Holleboom, A. G., & Cabezas, M. C. (2025) · European Journal of Clinical Investigation · doi:10.1111/eci.70003 · Cited by 28 · see citing works
The impact of sodium glucose co‐transporter 2 inhibitors on non‐alcoholic fatty liver disease
Chrysavgis, L., Papatheodoridi, A., Chatzigeorgiou, A., & Cholongitas, Ε. (2020) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.15202 · Cited by 26 · see citing works
At the Crossroads of Health and Disease: Consequences of Fat in the Liver
Dukewich, M., Yuan, L., & Terrault, N. A. (2025) · Annual Review of Physiology · doi:10.1146/annurev-physiol-022724-105515 · Cited by 28 · see citing works
Diaconu, C.-T., & Guja, C. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11175144 · Cited by 28 · see citing works
Emerging and Established Therapeutic Approaches for Nonalcoholic Fatty Liver Disease
Brown, E. E., Hydes, T., Hamid, A., & Cuthbertson, D. J. (2021) · Clinical Therapeutics · doi:10.1016/j.clinthera.2021.07.013 · Cited by 24 · see citing works
Colosimo, S., Tan, G. D., Petroni, M. L., Marchesini, G., & Tomlinson, J. (2022) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2022.12.010 · Cited by 25 · see citing works
NAFLD and type 2 diabetes: A practical guide for the joint management
Genua, I., Iruzubieta, P., Rodríguez-Duque, J. C., Pérez, A., & Crespo, J. (2022) · Gastroenterología y Hepatología · doi:10.1016/j.gastrohep.2022.12.002 · Cited by 23 · see citing works
Review of current and new drugs for the treatment of metabolic-associated fatty liver disease
Gish, R. G., Fan, J., Dossaji, Z., Fichez, J., Laeeq, T., Chun, M. J., & Boursier, J. (2024) · Hepatology International · doi:10.1007/s12072-024-10698-y · Cited by 24 · see citing works
Song, T., Chen, S., Zhao, H., Wang, F., Song, H., Tian, D., Yang, Q., & Qi, L. (2021) · Hepatology Research · doi:10.1111/hepr.13645 · Cited by 23 · see citing works
Allen, A. M., Charlton, M., Cusi, K. J., Harrison, S. A., Kowdley, K. V., Noureddin, M., & Shubrook, J. H. (2024) · Postgraduate Medicine · doi:10.1080/00325481.2024.2325332 · Cited by 22 · see citing works
Self-citationJung, C., & Mok, J. (2019) · Journal of Obesity & Metabolic Syndrome · doi:10.7570/jomes.2019.28.1.18 · Cited by 22 · see citing works
Hydes, T. J., Summers, N., Brown, E., Alam, U., Thomaides‐Brears, H., Wilding, J. P. H., & Cuthbertson, D. J. (2020) · Diabetic Medicine · doi:10.1111/dme.14356 · Cited by 21 · see citing works
Anti-diabetic drugs and NASH: from current options to promising perspectives
Smati, S., Canivet, C. M., Boursier, J., & Cariou, B. (2021) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2021.1951701 · Cited by 21 · see citing works
- Authors
- Cusi, K., Bril, F., Barb, D., Polidori, D., Sha, S., Ghosh, A., Farrell, K., Sunny, N. E., Kalavalapalli, S., Pettus, J., Ciaraldi, T. P., Mudaliar, S., & Henry, R. R.
- Affiliations
- University of Florida Health (US)
- Janssen Research & Development LLC San Diego California
- Janssen Research & Development (United States) (US)
- University of California San Diego (US)
- Corresponding author
- Cusi, Kenneth
- ORCID
- Venue
- Diabetes, Obesity and Metabolism
- Publisher
- Wiley
- Published
- 2018-12-18
- Volume
- 21
- Issue
- 4
- Pages
- 812-821
- ISSN
- 1462-8902 (ISSN-L)
- 1463-1326
- OpenAlex
- W2901946789
- Cited by
- 204
- References
- 42
- Citations by year
- 2026: 18 · 2025: 28 · 2024: 27 · 2023: 26 · 2022: 33 · 2021: 33 · 2020: 29 · 2019: 9 · 2015: 1
- FWCI
- 14.13
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes Obesity and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Janssen Research & Development, LLC
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- canagliflozin, SGLT2 inhibitors, type 2 diabetes, hepatic steatosis, non-alcoholic fatty liver disease, hepatic insulin sensitivity, beta-cell function, glucose metabolism, weight loss, HbA1c, insulin clearance, disposition index, 1H NMR
- MeSH terms
- Canagliflozin, Sodium-Glucose Transporter 2 Inhibitors, Insulin Secretion, Aged, Diabetes Mellitus, Type 2, Double-Blind Method, Female, Glycated Hemoglobin, Humans, Insulin Resistance, Liver, Male, Middle Aged, Triglycerides, Glucose Clamp Technique, Weight Loss, Treatment Outcome, Insulin-Secreting Cells, Proton Magnetic Resonance Spectroscopy
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