138-OR: 在1型糖尿病患者中,吡格列酮可放大达帕格列净引起的HbA1c降低幅度并防止血浆酮体升高

IF 6.2 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Diabetes Pub Date : 2024-07-19 DOI:10.2337/db24-138-or
MUHAMMAD ABDUL-GHANI, GOZDE BASKOY, AFIF NAKHLEH, SIHAM ABDELGANI, FAHD AL-MULLA, MOHAMED ABU-FARHA, FAHAD ALAJMI, THAMER ALESSA, RALPH A. DEFRONZO, NAIM SHEHADEH
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Results: T1DM patients were 42±3 years of age, 30% female, BMI=26.8±0.7, HbA1c=8.5±0.2%, insulin dose= 63±4 units, and eGFR=114±6 ml/min. Dapagliflozin caused -0.63±0.18%, and -0.56±0.11% decrease from baseline in HbA1c at week 16 in subjects receiving pioglitazone and placebo, respectively (both p<0.001). At week 32, the decrease from baseline in HbA1c was -0.86±0.3 and -0.44±0.17 in subjects receiving pioglitazone and placebo, respectively. Thus, the HbA1c was -0.42±0.12 lower in subjects receiving pioglitazone versus placebo (p<0.05). Plasma ketone concentration increased above baseline by 0.12±0.03 mM and 0.14±0.03 mM at week 16 in subjects receiving pioglitazone and placebo, respectively (both p<0.05). At week 32 plasma ketone concentration remained elevated above baseline in subjects receiving placebo (0.15±0.03 mM, p<0.05), and decreased below baseline (-0.06±0.02mM, p<0.05) in subjects receiving pioglitazone. Thus, the difference in plasma ketone concentration between subjects receiving pioglitazone and placebo at week 32 was -0.19±0.3, p<0.001. Conclusion: Addition of pioglitazone to SGLT2i in T1DM patients amplifies the decrease in HbA1c and prevents the increase in plasma ketone caused by SGLT2i, allowing long-term cardiovascular and renal outcome studies to be carried out safely in T1DM patients. Disclosure M. Abdul-Ghani: None. G. Baskoy: None. A. Nakhleh: None. S. Abdelgani: None. F. Al-Mulla: None. M. Abu-farha: None. F. Alajmi: Consultant; Novo Nordisk. Research Support; Novo Nordisk. Speaker's Bureau; Novo Nordisk. T. Alessa: None. R.A. DeFronzo: Advisory Panel; AstraZeneca, Novo Nordisk, Boehringer-Ingelheim, Intarcia Therapeutics, Inc., Aardvark, Renalytix, Corcept Therapeutics, Alnylam Pharmaceuticals, Inc. Research Support; Boehringer-Ingelheim, AstraZeneca, 89bio, Inc., Amgen Inc., Medality, Corcept Therapeutics. Speaker's Bureau; AstraZeneca, Corcept Therapeutics, Renalytix. N. Shehadeh: Research Support; Abbott. Advisory Panel; AstraZeneca, Eli Lilly and Company, Boehringer-Ingelheim. Research Support; Novo Nordisk Foundation. Funding The study was funded by JDRF grant to MAG. Astrazeneca provided dapagliflozin.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"35 1","pages":""},"PeriodicalIF":6.2000,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"138-OR: Pioglitazone Amplifies the Decrease in HbA1c and Prevents the Increase in Plasma Ketone Caused by Dapagliflozin in Type 1 Diabetes Mellitus Patients\",\"authors\":\"MUHAMMAD ABDUL-GHANI, GOZDE BASKOY, AFIF NAKHLEH, SIHAM ABDELGANI, FAHD AL-MULLA, MOHAMED ABU-FARHA, FAHAD ALAJMI, THAMER ALESSA, RALPH A. 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Dapagliflozin caused -0.63±0.18%, and -0.56±0.11% decrease from baseline in HbA1c at week 16 in subjects receiving pioglitazone and placebo, respectively (both p<0.001). At week 32, the decrease from baseline in HbA1c was -0.86±0.3 and -0.44±0.17 in subjects receiving pioglitazone and placebo, respectively. Thus, the HbA1c was -0.42±0.12 lower in subjects receiving pioglitazone versus placebo (p<0.05). Plasma ketone concentration increased above baseline by 0.12±0.03 mM and 0.14±0.03 mM at week 16 in subjects receiving pioglitazone and placebo, respectively (both p<0.05). At week 32 plasma ketone concentration remained elevated above baseline in subjects receiving placebo (0.15±0.03 mM, p<0.05), and decreased below baseline (-0.06±0.02mM, p<0.05) in subjects receiving pioglitazone. Thus, the difference in plasma ketone concentration between subjects receiving pioglitazone and placebo at week 32 was -0.19±0.3, p<0.001. 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引用次数: 0

摘要

引言和目的:SGLT2 抑制剂(SGLT2i)可降低 T1DM 患者的血浆葡萄糖浓度。然而,它们会导致血浆酮体浓度升高和酮症酸中毒的风险。本研究旨在探讨吡格列酮是否会放大 HbA1c 的降低幅度,并防止达帕格列净引起 T1DM 患者血浆酮体浓度的升高。研究方法60名T1DM患者在经过4周的适应期后,接受10毫克达帕格列净治疗12周。第 16 周时,患者被随机分配接受双盲方式的吡格列酮治疗(45 毫克)或相应的安慰剂治疗,疗程再延长 16 周。研究结果T1DM患者年龄为42±3岁,30%为女性,BMI=26.8±0.7,HbA1c=8.5±0.2%,胰岛素剂量=63±4单位,eGFR=114±6毫升/分钟。在第16周,接受吡格列酮和安慰剂的受试者的HbA1c分别比基线下降-0.63±0.18%和-0.56±0.11%(均为p<0.001)。第32周时,接受吡格列酮治疗的受试者和接受安慰剂治疗的受试者的HbA1c与基线相比的降幅分别为-0.86±0.3和-0.44±0.17。因此,与安慰剂相比,接受吡格列酮治疗的受试者的 HbA1c 降低了-0.42±0.12(p<0.05)。在第 16 周,接受吡格列酮治疗的受试者和接受安慰剂治疗的受试者的血浆酮浓度分别比基线增加了 0.12±0.03 mM 和 0.14±0.03 mM(均为 p<0.05)。在第32周,接受安慰剂的受试者血浆酮浓度仍高于基线(0.15±0.03 mM,p<0.05),而接受吡格列酮的受试者则低于基线(-0.06±0.02mM,p<0.05)。因此,在第32周时,接受吡格列酮治疗的受试者与接受安慰剂治疗的受试者之间的血浆酮浓度差异为-0.19±0.3,p<0.001。结论T1DM患者在服用SGLT2i的基础上加用吡格列酮,可扩大HbA1c的降幅,并防止SGLT2i引起的血浆酮体升高,从而可在T1DM患者中安全地开展长期心血管和肾脏结局研究。披露 M. Abdul-Ghani:无。G. Baskoy:无:无。A. Nakhleh:无:无。S. Abdelgani:无。F. Al-Mulla:无。M. Abu-farha:M. Abu-farha: None.F. Alajmi:顾问;诺和诺德公司。研究支持;诺和诺德。发言人办公室;诺和诺德。T. Alessa:无。R.A. DeFronzo:顾问团;阿斯利康、诺和诺德、勃林格殷格翰、Intarcia Therapeutics, Inc.、Aardvark、Renalytix、Corcept Therapeutics、Alnylam Pharmaceuticals, Inc.研究支持;勃林格殷格翰公司、阿斯利康公司、89bio 公司、安进公司、Medality 公司、Corcept Therapeutics 公司。演讲人办公室;阿斯利康、Corcept Therapeutics、Renalytix。N. Shehadeh:研究支持;雅培顾问团;阿斯利康、礼来公司、勃林格殷格翰。研究支持;诺和诺德基金会。资金来源 本研究由 JDRF 资助 MAG。阿斯利康提供达帕格列净。
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138-OR: Pioglitazone Amplifies the Decrease in HbA1c and Prevents the Increase in Plasma Ketone Caused by Dapagliflozin in Type 1 Diabetes Mellitus Patients
Introduction and Objectives: SGLT2 inhibitors (SGLT2i) lower the plasma glucose concentration in T1DM patients. However, they cause an increase in plasma ketone concentration and risk of ketoacidosis. The aim of the present study is to examine whether pioglitazone amplifies the decrease in HbA1c and prevents the increase in plasma ketone concentration caused by dapagliflozin in T1DM patients. Methods: After a 4-week run in period, 60 T1DM patients received dapagliflozin 10 mg for 12 weeks. At week 16 patients were randomized to receive in double blind fashion pioglitazone (45 mg) or matching placebo for an additional 16 weeks. Results: T1DM patients were 42±3 years of age, 30% female, BMI=26.8±0.7, HbA1c=8.5±0.2%, insulin dose= 63±4 units, and eGFR=114±6 ml/min. Dapagliflozin caused -0.63±0.18%, and -0.56±0.11% decrease from baseline in HbA1c at week 16 in subjects receiving pioglitazone and placebo, respectively (both p<0.001). At week 32, the decrease from baseline in HbA1c was -0.86±0.3 and -0.44±0.17 in subjects receiving pioglitazone and placebo, respectively. Thus, the HbA1c was -0.42±0.12 lower in subjects receiving pioglitazone versus placebo (p<0.05). Plasma ketone concentration increased above baseline by 0.12±0.03 mM and 0.14±0.03 mM at week 16 in subjects receiving pioglitazone and placebo, respectively (both p<0.05). At week 32 plasma ketone concentration remained elevated above baseline in subjects receiving placebo (0.15±0.03 mM, p<0.05), and decreased below baseline (-0.06±0.02mM, p<0.05) in subjects receiving pioglitazone. Thus, the difference in plasma ketone concentration between subjects receiving pioglitazone and placebo at week 32 was -0.19±0.3, p<0.001. Conclusion: Addition of pioglitazone to SGLT2i in T1DM patients amplifies the decrease in HbA1c and prevents the increase in plasma ketone caused by SGLT2i, allowing long-term cardiovascular and renal outcome studies to be carried out safely in T1DM patients. Disclosure M. Abdul-Ghani: None. G. Baskoy: None. A. Nakhleh: None. S. Abdelgani: None. F. Al-Mulla: None. M. Abu-farha: None. F. Alajmi: Consultant; Novo Nordisk. Research Support; Novo Nordisk. Speaker's Bureau; Novo Nordisk. T. Alessa: None. R.A. DeFronzo: Advisory Panel; AstraZeneca, Novo Nordisk, Boehringer-Ingelheim, Intarcia Therapeutics, Inc., Aardvark, Renalytix, Corcept Therapeutics, Alnylam Pharmaceuticals, Inc. Research Support; Boehringer-Ingelheim, AstraZeneca, 89bio, Inc., Amgen Inc., Medality, Corcept Therapeutics. Speaker's Bureau; AstraZeneca, Corcept Therapeutics, Renalytix. N. Shehadeh: Research Support; Abbott. Advisory Panel; AstraZeneca, Eli Lilly and Company, Boehringer-Ingelheim. Research Support; Novo Nordisk Foundation. Funding The study was funded by JDRF grant to MAG. Astrazeneca provided dapagliflozin.
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来源期刊
Diabetes
Diabetes 医学-内分泌学与代谢
CiteScore
12.50
自引率
2.60%
发文量
1968
审稿时长
1 months
期刊介绍: Diabetes is a scientific journal that publishes original research exploring the physiological and pathophysiological aspects of diabetes mellitus. We encourage submissions of manuscripts pertaining to laboratory, animal, or human research, covering a wide range of topics. Our primary focus is on investigative reports investigating various aspects such as the development and progression of diabetes, along with its associated complications. We also welcome studies delving into normal and pathological pancreatic islet function and intermediary metabolism, as well as exploring the mechanisms of drug and hormone action from a pharmacological perspective. Additionally, we encourage submissions that delve into the biochemical and molecular aspects of both normal and abnormal biological processes. However, it is important to note that we do not publish studies relating to diabetes education or the application of accepted therapeutic and diagnostic approaches to patients with diabetes mellitus. Our aim is to provide a platform for research that contributes to advancing our understanding of the underlying mechanisms and processes of diabetes.
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