diaendoСахарный диабетDiabetes mellitus2072-03512072-0378Endocrinology research centre10.14341/DM13340diaendo-13340Research ArticleОригинальные исследованияOriginal StudiesИпраглифлозин улучшает состояние печени у пациентов с сахарным диабетом с неалкогольной жировой болезнью печениIpragliflozin improves the hepatic outcomes of patients with diabetes with NAFLDhttps://orcid.org/0000-0002-5014-9239TakahashiHirokazuTakahashiHirokazu

Hirokazu Takahashi, MD, PhD, Liver Center, Saga University Hospital, Faculty of Medicine, Saga University

5-1-1 Набешима, Сага-Сити, Сага

 

Hirokazu Takahashi, MD, PhD, Liver Center, Saga University Hospital, Faculty of Medicine, Saga University

5-1-1 Nabeshima, Saga City, Saga

takahas2@cc.saga-u.ac.jpKessokuTakaomiKessokuTakaomi

Кафедра гастроэнтерологии и гепатологии, аспирантура медицинского факультета

Йокогама

Department of Gastroenterology and Hepatology, Graduate School of Medicine

Yokohama

takahas2@cc.saga-u.ac.jpKawanakaMiwaKawanakaMiwa

M.D., Ph.D.

Окаяма

Department of General Internal Medicine Kawasaki Medical Center

Okayama

akeizo@cc.saga-u.ac.jpNonakaMichihiroNonakaMichihiro

Отделение гастроэнтерологии и гепатологии

Хацукаичи

Department of Gastroenterology and Hepatology

Hatsukaichi

HyogoHideyukiHyogoHideyuki

Отделение гастроэнтерологии и гепатологии

Хацукаичи

Department of Gastroenterology and Hepatology

Hatsukaichi

FujiiHidekiFujiiHideki

Отделение гастроэнтерологии и гепатологии, больница района Джусо.

Кафедра первичной профилактической медицины, аспирантура медицинского факультета Университета г. Осака

Осака

Department of Gastroenterology and Hepatology, Osaka City Juso Hospital.

Department of Premier Preventive Medicine, Osaka City University Graduate School of Medicine

Osaka

NakajimaTomoakiNakajimaTomoaki

Department of Hepatology

Sapporo

ImajoKentoImajoKento

Кафедра гастроэнтерологии и гепатологии, аспирантура медицинского факультета

Йокогама

Department of Gastroenterology and Hepatology, Graduate School of Medicine

Yokohama

TanakaKenichiTanakaKenichi

Отделение метаболизма и эндокринологии, медицинский факультет

Сага

Division of Metabolism and Endocrinology, Faculty of Medicine

Saga

KubotsuYoshihitoKubotsuYoshihito

Отделение метаболизма и эндокринологии, медицинский факультет

Сага

Division of Metabolism and Endocrinology, Faculty of Medicine

Saga

IsodaHiroshiIsodaHiroshi

Центр гепатологии, клиника Университета Саги, медицинский факультет

Сага

Liver Center, Saga University Hospital, Faculty of Medicine

Saga

OedaSatoshiOedaSatoshi

Центр гепатологии, клиника Университета Саги, медицинский факультет

Сага

Liver Center, Saga University Hospital, Faculty of Medicine

Saga

KuraiOsamuKuraiOsamu

Отделение гастроэнтерологии и гепатологии

Осака

Department of Gastroenterology and Hepatology

Osaka

YonedaMasatoYonedaMasato

Кафедра гастроэнтерологии и гепатологии, аспирантура медицинского факультета

Йокогама

Department of Gastroenterology and Hepatology, Graduate School of Medicine, 

Yokohama

OnoMasafumiOnoMasafumi

Отделение внутренних болезней, медицинский центр 

Токио

Internal Medicine

Tokyo

KitajimaYoichiroKitajimaYoichiro

Отделение метаболизма и эндокринологии, медицинский факультет, Университет Саги

Отделение гастроэнтерологии, больница Эгучи

Сага, Оги

Division of Metabolism and Endocrinology, Faculty of Medicine, Saga University.

Department of Clinical Gastroenterology, Eguchi Hospital

Saga, Ogi

TajiriRyoTajiriRyo

Клинический научный центр

Сага

Clinical Research Center

Saga

TakamoriAyakoTakamoriAyako

Клинический научный центр

Сага

Clinical Research Center

Saga

KawaguchiAtsushiKawaguchiAtsushi

Научно-образовательный центр общественной медицины, медицинский факультет

Сага

Education and Research Center for Community Medicine, Faculty of Medicine

Saga

AishimaShinichiAishimaShinichi

Кафедра патологии и микробиологии, медицинский факультет

Сага

Department of Pathology and Microbiology, Faculty of Medicine

Saga

KageMasayoshiKageMasayoshi

Научно-исследовательский центр инновационной терапии рака 

Куруме

Research Center for Innovative Cancer Therapy

Kurume

NakajimaAtsushiNakajimaAtsushi

Кафедра гастроэнтерологии и гепатологии, аспирантура медицинского факультета

Йокогама

Department of Gastroenterology and Hepatology, Graduate School of Medicine

Yokohama

EguchiYuichiroEguchiYuichiro

Центр гепатологии, клиника Университета Саги, медицинский факультет

Сага

Liver Center, Saga University Hospital, Faculty of Medicine

Saga

AnzaiKeizoAnzaiKeizo

Keizo Anzai, MD, PhD, Division of Metabolism and Endocrinology, Faculty of Medicine

5-1-1 Набешима, Сага-Сити, Сага

Keizo Anzai, MD, PhD, Division of Metabolism and Endocrinology, Faculty of Medicine

5-1-1 Nabeshima, Saga City, Saga

akeizo@cc.saga-u.ac.jpУниверситет СагиЯпонияSaga UniversityJapanУниверситет ЙокогамыЯпонияYokohama City UniversityJapanМедицинский университет КавасакиЯпонияKawasaki Medical SchoolJapanБольница общего профиля Хиросимы JAЯпонияJA Hiroshima General HospitalJapanБольница района Джусо; Университет г. ОсакаЯпонияOsaka City Juso Hospital; Osaka City University Graduate School of MedicineJapanБольница общего профиля Саппоро КосейЯпонияSapporo Kosei General HospitalJapanБольница района ДжусоЯпонияOsaka City Juso HospitalJapanТокийский женский медицинский университетЯпонияTokyo Women’s Medical University Medical Center EastJapanУниверситет Саги; Больница ЭгучиЯпонияSaga University; Eguchi HospitalJapanКлиника университета СагиЯпонияSaga University HospitalJapanУниверситета КурумеЯпонияKurume UniversityJapan202523052025282210227Copyright © Takahashi H., Kessoku T., Kawanaka M., Nonaka M., Hyogo H., Fujii H., Nakajima T., Imajo K., Tanaka K., Kubotsu Y., Isoda H., Oeda S., Kurai O., Yoneda M., Ono M., Kitajima Y., Tajiri R., Takamori A., Kawaguchi A., Aishima S., Kage M., Nakajima A., Eguchi Y., Anzai K., 20252025Takahashi H., Kessoku T., Kawanaka M., Nonaka M., Hyogo H., Fujii H., Nakajima T., Imajo K., Tanaka K., Kubotsu Y., Isoda H., Oeda S., Kurai O., Yoneda M., Ono M., Kitajima Y., Tajiri R., Takamori A., Kawaguchi A., Aishima S., Kage M., Nakajima A., Eguchi Y., Anzai K.Takahashi H., Kessoku T., Kawanaka M., Nonaka M., Hyogo H., Fujii H., Nakajima T., Imajo K., Tanaka K., Kubotsu Y., Isoda H., Oeda S., Kurai O., Yoneda M., Ono M., Kitajima Y., Tajiri R., Takamori A., Kawaguchi A., Aishima S., Kage M., Nakajima A., Eguchi Y., Anzai K.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.dia-endojournals.ru/jour/article/view/13340

Ингибиторы натрий-глюкозного котранспортера 2-го типа (иНГЛТ-2) широко применяются для лечения сахарного диабета, однако их влияние на неалкогольную жировую болезнь печени (НАЖБП) еще предстоит определить.

Цель нашего исследования — оценка влияния иНГЛТ-2 на патогенез НАЖБП. Проведено многоцентровое рандомизированное контролируемое исследование с участием пациентов с сахарным диабетом 2 типа, страдающих НАЖБП. Сравнивали изменения гликемического контроля, жировой массы и патологии печени между группой участников, получавших ипраглифлозин (50 мг/сут в течение 72 нед.; группа ИПР), и группой участников, которые не принимали иНГЛТ-2, пиоглитазон, аналоги глюкагоноподобного пептида-1 или инсулин (контрольная группа, КОНТР). В группе ИПР (n=25) за период исследования установлено статистически значимое снижение концентрации гликированного гемоглобина (HbA1c) и индекса массы тела (ИМТ) (HbA1c: –0,41%, P<0,01; ИМТ: –1,06 кг/m2, P<0,01), в то время как в контрольной группе (n=26) эти показатели не изменились. Морфологическое состояние печени было оценено у 21 участника в группе ИПР и у 25 участников в контрольной группе. Исходно у 17 (81%) пациентов в группе ИПР и у 18 (72%) в контрольной группе КОНТР имелся фиброз печени. Показатели фиброза улучшились у 70,6% (12 из 17) участников в группе ИПР и у 22% (4 из 18) участников в контрольной группе (Р<0,01). Разрешение неалкогольного стеатогепатита (НАСГ) отмечено у 66,7% пациентов, получавших ипраглифлозин, и у 27,3% участников контрольной группы. Ни у одного из пациентов в группе ИПР не развился НАСГ, тогда как в контрольной группе НАСГ развился у 33,3% участников.

ЗАКЛЮЧЕНИЕ. Длительное лечение ипраглифлозином улучшает показатели фиброза печени у пациентов с НАЖБП. Следовательно, ипраглифлозин может быть эффективен для лечения и профилактики НАСГ у пациентов с сахарным диабетом, а также для улучшения гликемического контроля и уменьшения жировой массы. Таким образом, иНГЛТ-2 представляют перспективный вариант лечения пациентов с сахарным диабетом с НАЖБП, однако для подтверждения обнаруженных эффектов требуются дальнейшие более крупные исследования (Hepatology Communications 2022;6:120-132).

Sodium glucose cotransporter-2 inhibitors (SGLT2is) are now widely used to treat diabetes, but their effects on nonalcoholic fatty liver disease (NAFLD) remain to be determined. We aimed to evaluate the effects of SGLT2is on the pathogenesis of NAFLD. A multicenter, randomized, controlled trial was conducted in patients with type 2 diabetes with NAFLD. The changes in glycemic control, obesity, and liver pathology were compared between participants taking ipragliflozin (50 mg/day for 72 weeks; IPR group) and participants being managed without SGLT2is, pioglitazone, glucagon-like peptide-1 analogs, or insulin (CTR group). In the IPR group (n = 25), there were significant decreases in hemoglobin A1c (HbA1c) and body mass index (BMI) during the study (HbA1c, -0.41%, P < 0.01; BMI, -1.06 kg/m2, P < 0.01), whereas these did not change in the CTR group (n = 26). Liver pathology was evaluated in 21/25 participants in the IPR/CTR groups, and hepatic fibrosis was found in 17 (81%) and 18 (72%) participants in the IPR and CTR groups at baseline. This was ameliorated in 70.6% (12 of 17) of participants in the IPR group and 22.2 % (4 of 18). of those in the CTR group (P < 0.01). Nonalcoholic steatohepatitis (NASH) resolved in 66.7% of IPR-treated participants and 27.3% of CTR participants. None of the participants in the IPR group developed NASH, whereas 33.3% of the CTR group developed NASH. Conclusion: Long-term ipragliflozin treatment ameliorates hepatic fibrosis in patients with NAFLD. Thus, ipragliflozin might be effective for the treatment and prevention of NASH in patients with diabetes, as well as improving glycemic control and obesity. Therefore, SGLT2is may represent a therapeutic choice for patients with diabetes with NAFLD, but further larger studies are required to confirm these effects. (Hepatology Communications 2022;6:120-132) .

Sodium glucose cotransporter-2 inhibitors (SGLT2is) are now widely used to treat diabetes, but their effects on nonalcoholic fatty liver disease (NAFLD) remain to be determined. We aimed to evaluate the effects of SGLT2is on the pathogenesis of NAFLD. A multicenter, randomized, controlled trial was conducted in patients with type 2 diabetes with NAFLD. The changes in glycemic control, obesity, and liver pathology were compared between participants taking ipragliflozin (50 mg/day for 72 weeks; IPR group) and participants being managed without SGLT2is, pioglitazone, glucagon-like peptide-1 analogs, or insulin (CTR group). In the IPR group (n = 25), there were significant decreases in hemoglobin A1c (HbA1c) and body mass index (BMI) during the study (HbA1c, -0.41%, P < 0.01; BMI, -1.06 kg/m2, P < 0.01), whereas these did not change in the CTR group (n = 26). Liver pathology was evaluated in 21/25 participants in the IPR/CTR groups, and hepatic fibrosis was found in 17 (81%) and 18 (72%) participants in the IPR and CTR groups at baseline. This was ameliorated in 70.6% (12 of 17) of participants in the IPR group and 22.2 % (4 of 18). of those in the CTR group (P < 0.01). Nonalcoholic steatohepatitis (NASH) resolved in 66.7% of IPR-treated participants and 27.3% of CTR participants. None of the participants in the IPR group developed NASH, whereas 33.3% of the CTR group developed NASH.

Conclusion: Long-term ipragliflozin treatment ameliorates hepatic fibrosis in patients with NAFLD. Thus, ipragliflozin might be effective for the treatment and prevention of NASH in patients with diabetes, as well as improving glycemic control and obesity. Therefore, SGLT2is may represent a therapeutic choice for patients with diabetes with NAFLD, but further larger studies are required to confirm these effects. (Hepatology Communications 2022;6:120-132) .

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The authors declare that there are no conflicts of interest present.