Vikas S Sridhar, Ayodele Odutayo, Satish Garg, Thomas Danne, Alessandro Doria, Michael Mauer, Michael J Davies, Phillip Banks, Manon Girard, David Z I Cherney
{"title":"索他利氟嗪对 1 型糖尿病合并慢性肾脏病患者的疗效和安全性。","authors":"Vikas S Sridhar, Ayodele Odutayo, Satish Garg, Thomas Danne, Alessandro Doria, Michael Mauer, Michael J Davies, Phillip Banks, Manon Girard, David Z I Cherney","doi":"10.1681/ASN.0000000540","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>This analysis evaluated the efficacy and safety of sotagliflozin, a dual SGLT1&2 inhibitor, added to insulin in patients with type 1 diabetes and chronic kidney disease (CKD).</p><p><strong>Methods: </strong>We used data from the 52-week pooled inTandem1&2 trials and the 24-week inTandem3 trial to assess the effects of sotagliflozin (200mg [inTandem 1&2 only] or 400mg daily) versus placebo on glycated hemoglobin (HbA1c; primary endpoint), body weight, systolic blood pressure (BP), insulin dose, and safety endpoints including adjudicated severe hypoglycemia and diabetic ketoacidosis (DKA), stratified by CKD.</p><p><strong>Results: </strong>CKD was identified in 237/1575 of inTandem1&2 participants and 228/1402 of inTandem3 participants. At week-24, significant, placebo-adjusted reductions in HbA1c were observed - inTandem1&2: Non-CKD subgroup (sotagliflozin 200mg: -0.4%, 95% CI -0.4 to -0.3; 400mg: -0.4%, 95% CI -0.5 to -0.3) and CKD subgroup (sotagliflozin 200mg: -0.4%, 95% CI -0.6 to -0.1; 400mg: -0.3%, 95% CI -0.5 to -0.1). For systolic BP, there was a significant reduction at week-24 with sotagliflozin in the non-CKD subgroup but no effect in the CKD subgroup in inTandem1&2. At week-52, the incidence of severe hypoglycemia was lower with sotagliflozin (7% on 200 mg and 4% on 400 mg) compared to placebo (17%) in the CKD subgroup of inTandem1&2, whereas the incidence of severe hypoglycemia was 5-6% across non-CKD subgroups. The incidence of adjudicated DKA at week-52 was 1%, 5%, and 3% for placebo, 200 mg, and 400 mg in the CKD subgroup compared to 0%, 3%, and 4% in the non-CKD subgroup. Results were generally similar in inTandem3 except systolic BP was significantly reduced with sotagliflozin versus placebo in CKD and non-CKD subgroups.</p><p><strong>Conclusions: </strong>In participants with type 1 diabetes and CKD, sotagliflozin treatment had similar HbA1c, body weight, and systolic BP lowering effects as in participants with type 1 diabetes without CKD. Additionaly, sotagliflozin was associated with a lower to neutral risk of severe hypoglycemia and did not significantly increase the risk of DKA among a small number of DKA events.</p>","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Efficacy and Safety of Sotagliflozin in Patients with Type 1 Diabetes and CKD.\",\"authors\":\"Vikas S Sridhar, Ayodele Odutayo, Satish Garg, Thomas Danne, Alessandro Doria, Michael Mauer, Michael J Davies, Phillip Banks, Manon Girard, David Z I Cherney\",\"doi\":\"10.1681/ASN.0000000540\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>This analysis evaluated the efficacy and safety of sotagliflozin, a dual SGLT1&2 inhibitor, added to insulin in patients with type 1 diabetes and chronic kidney disease (CKD).</p><p><strong>Methods: </strong>We used data from the 52-week pooled inTandem1&2 trials and the 24-week inTandem3 trial to assess the effects of sotagliflozin (200mg [inTandem 1&2 only] or 400mg daily) versus placebo on glycated hemoglobin (HbA1c; primary endpoint), body weight, systolic blood pressure (BP), insulin dose, and safety endpoints including adjudicated severe hypoglycemia and diabetic ketoacidosis (DKA), stratified by CKD.</p><p><strong>Results: </strong>CKD was identified in 237/1575 of inTandem1&2 participants and 228/1402 of inTandem3 participants. At week-24, significant, placebo-adjusted reductions in HbA1c were observed - inTandem1&2: Non-CKD subgroup (sotagliflozin 200mg: -0.4%, 95% CI -0.4 to -0.3; 400mg: -0.4%, 95% CI -0.5 to -0.3) and CKD subgroup (sotagliflozin 200mg: -0.4%, 95% CI -0.6 to -0.1; 400mg: -0.3%, 95% CI -0.5 to -0.1). For systolic BP, there was a significant reduction at week-24 with sotagliflozin in the non-CKD subgroup but no effect in the CKD subgroup in inTandem1&2. At week-52, the incidence of severe hypoglycemia was lower with sotagliflozin (7% on 200 mg and 4% on 400 mg) compared to placebo (17%) in the CKD subgroup of inTandem1&2, whereas the incidence of severe hypoglycemia was 5-6% across non-CKD subgroups. The incidence of adjudicated DKA at week-52 was 1%, 5%, and 3% for placebo, 200 mg, and 400 mg in the CKD subgroup compared to 0%, 3%, and 4% in the non-CKD subgroup. Results were generally similar in inTandem3 except systolic BP was significantly reduced with sotagliflozin versus placebo in CKD and non-CKD subgroups.</p><p><strong>Conclusions: </strong>In participants with type 1 diabetes and CKD, sotagliflozin treatment had similar HbA1c, body weight, and systolic BP lowering effects as in participants with type 1 diabetes without CKD. Additionaly, sotagliflozin was associated with a lower to neutral risk of severe hypoglycemia and did not significantly increase the risk of DKA among a small number of DKA events.</p>\",\"PeriodicalId\":17217,\"journal\":{\"name\":\"Journal of The American Society of Nephrology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":10.3000,\"publicationDate\":\"2024-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of The American Society of Nephrology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1681/ASN.0000000540\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"UROLOGY & NEPHROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of The American Society of Nephrology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1681/ASN.0000000540","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"UROLOGY & NEPHROLOGY","Score":null,"Total":0}
Efficacy and Safety of Sotagliflozin in Patients with Type 1 Diabetes and CKD.
Background: This analysis evaluated the efficacy and safety of sotagliflozin, a dual SGLT1&2 inhibitor, added to insulin in patients with type 1 diabetes and chronic kidney disease (CKD).
Methods: We used data from the 52-week pooled inTandem1&2 trials and the 24-week inTandem3 trial to assess the effects of sotagliflozin (200mg [inTandem 1&2 only] or 400mg daily) versus placebo on glycated hemoglobin (HbA1c; primary endpoint), body weight, systolic blood pressure (BP), insulin dose, and safety endpoints including adjudicated severe hypoglycemia and diabetic ketoacidosis (DKA), stratified by CKD.
Results: CKD was identified in 237/1575 of inTandem1&2 participants and 228/1402 of inTandem3 participants. At week-24, significant, placebo-adjusted reductions in HbA1c were observed - inTandem1&2: Non-CKD subgroup (sotagliflozin 200mg: -0.4%, 95% CI -0.4 to -0.3; 400mg: -0.4%, 95% CI -0.5 to -0.3) and CKD subgroup (sotagliflozin 200mg: -0.4%, 95% CI -0.6 to -0.1; 400mg: -0.3%, 95% CI -0.5 to -0.1). For systolic BP, there was a significant reduction at week-24 with sotagliflozin in the non-CKD subgroup but no effect in the CKD subgroup in inTandem1&2. At week-52, the incidence of severe hypoglycemia was lower with sotagliflozin (7% on 200 mg and 4% on 400 mg) compared to placebo (17%) in the CKD subgroup of inTandem1&2, whereas the incidence of severe hypoglycemia was 5-6% across non-CKD subgroups. The incidence of adjudicated DKA at week-52 was 1%, 5%, and 3% for placebo, 200 mg, and 400 mg in the CKD subgroup compared to 0%, 3%, and 4% in the non-CKD subgroup. Results were generally similar in inTandem3 except systolic BP was significantly reduced with sotagliflozin versus placebo in CKD and non-CKD subgroups.
Conclusions: In participants with type 1 diabetes and CKD, sotagliflozin treatment had similar HbA1c, body weight, and systolic BP lowering effects as in participants with type 1 diabetes without CKD. Additionaly, sotagliflozin was associated with a lower to neutral risk of severe hypoglycemia and did not significantly increase the risk of DKA among a small number of DKA events.
期刊介绍：
The Journal of the American Society of Nephrology (JASN) stands as the preeminent kidney journal globally, offering an exceptional synthesis of cutting-edge basic research, clinical epidemiology, meta-analysis, and relevant editorial content. Representing a comprehensive resource, JASN encompasses clinical research, editorials distilling key findings, perspectives, and timely reviews.
Editorials are skillfully crafted to elucidate the essential insights of the parent article, while JASN actively encourages the submission of Letters to the Editor discussing recently published articles. The reviews featured in JASN are consistently erudite and comprehensive, providing thorough coverage of respective fields. Since its inception in July 1990, JASN has been a monthly publication.
JASN publishes original research reports and editorial content across a spectrum of basic and clinical science relevant to the broad discipline of nephrology. Topics covered include renal cell biology, developmental biology of the kidney, genetics of kidney disease, cell and transport physiology, hemodynamics and vascular regulation, mechanisms of blood pressure regulation, renal immunology, kidney pathology, pathophysiology of kidney diseases, nephrolithiasis, clinical nephrology (including dialysis and transplantation), and hypertension. Furthermore, articles addressing healthcare policy and care delivery issues relevant to nephrology are warmly welcomed.
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