Viral N Shah, Rikke M Agesen, Lars Bardtrum, Erik Christiansen, Jennifer Snaith, Jerry R Greenfield
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This paper aims to improve our understanding of the potential mechanisms leading to premature discontinuation of this treatment regimen.</p><p><strong>Methods: </strong>Post hoc comparisons were conducted on baseline characteristics and adverse event (AE) rates of participants completing and not completing the ADJUNCT studies due to AEs/lack of tolerance using summary tables and variance analysis.</p><p><strong>Results: </strong>Non-completers (liraglutide and placebo combined) had lower baseline body mass index (BMI) (ADJUNCT ONE: 27.8 kg/m<sup>2</sup> vs 29.8 kg/m<sup>2</sup>, <i>P</i> < .0001; ADJUNCT TWO: 26.3 kg/m<sup>2</sup> vs 29.2 kg/m<sup>2</sup>, <i>P</i> < .0001), longer duration of T1D (25.8 years vs 21.0 years, <i>P</i> < .0001; 24.1 years vs 21.0 years, <i>P</i> = .04), lower daily insulin doses by continuous infusion (46.4 U vs 57.3 U, <i>P</i> = .01; 40.9 U vs 57.4 U, <i>P</i> = .12) or multiple injections (58.4 U vs 68.5 U, <i>P</i> = .006; 56.0 U vs 65.8 U, <i>P</i> =.03) and a higher proportion of participants with undetectable C-peptide (91.5% vs 81.3%; 87.0% vs 84.9%) compared to completers. When analyzed by treatment group, only duration of T1D and C-peptide differed between completers and non-completers among liraglutide (and not placebo) participants. The AE rates were higher for non-completers.</p><p><strong>Conclusion: </strong>Individuals with longer-standing T1D and low levels of C-peptide at baseline were more likely to discontinue adjunctive liraglutide treatment due to AEs/lack of tolerance than individuals with residual insulin production. Lower BMI predicted a greater likelihood of non-completion for the included participants, regardless of treatment. These new findings may be relevant for clinical practice.</p>","PeriodicalId":15475,"journal":{"name":"Journal of Diabetes Science and Technology","volume":" ","pages":"19322968241305647"},"PeriodicalIF":4.1000,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669135/pdf/","citationCount":"0","resultStr":"{\"title\":\"Determinants of Liraglutide Treatment Discontinuation in Type 1 Diabetes: A Post Hoc Analysis of ADJUNCT ONE and ADJUNCT TWO Randomized Placebo-Controlled Clinical Studies.\",\"authors\":\"Viral N Shah, Rikke M Agesen, Lars Bardtrum, Erik Christiansen, Jennifer Snaith, Jerry R Greenfield\",\"doi\":\"10.1177/19322968241305647\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Two phase 3 randomized controlled studies (ADJUNCT ONE (Clinicaltrials.gov: NCT01836523), ADJUNCT TWO (Clinicaltrials.gov: NCT02098395)) evaluated liraglutide (1.8, 1.2 or 0.6 mg) vs placebo in participants with type 1 diabetes (T1D) as an adjunct to insulin therapy. This paper aims to improve our understanding of the potential mechanisms leading to premature discontinuation of this treatment regimen.</p><p><strong>Methods: </strong>Post hoc comparisons were conducted on baseline characteristics and adverse event (AE) rates of participants completing and not completing the ADJUNCT studies due to AEs/lack of tolerance using summary tables and variance analysis.</p><p><strong>Results: </strong>Non-completers (liraglutide and placebo combined) had lower baseline body mass index (BMI) (ADJUNCT ONE: 27.8 kg/m<sup>2</sup> vs 29.8 kg/m<sup>2</sup>, <i>P</i> < .0001; ADJUNCT TWO: 26.3 kg/m<sup>2</sup> vs 29.2 kg/m<sup>2</sup>, <i>P</i> < .0001), longer duration of T1D (25.8 years vs 21.0 years, <i>P</i> < .0001; 24.1 years vs 21.0 years, <i>P</i> = .04), lower daily insulin doses by continuous infusion (46.4 U vs 57.3 U, <i>P</i> = .01; 40.9 U vs 57.4 U, <i>P</i> = .12) or multiple injections (58.4 U vs 68.5 U, <i>P</i> = .006; 56.0 U vs 65.8 U, <i>P</i> =.03) and a higher proportion of participants with undetectable C-peptide (91.5% vs 81.3%; 87.0% vs 84.9%) compared to completers. 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引用次数: 0
摘要
两项3期随机对照研究（ADJUNCT ONE （Clinicaltrials.gov: NCT01836523）和ADJUNCT Two (Clinicaltrials.gov: NCT02098395)）评估了利拉鲁肽（1.8、1.2或0.6 mg）与安慰剂在1型糖尿病（T1D）患者中作为胰岛素治疗的辅助治疗。本文旨在提高我们对导致这种治疗方案过早停止的潜在机制的理解。方法：采用汇总表和方差分析，对完成和未完成ADJUNCT研究的参与者的基线特征和不良事件（AE）率进行事后比较。结果：未完成治疗者（利拉鲁肽和安慰剂联合）基线体重指数（BMI）较低(ADJUNCT ONE: 27.8 kg/m2 vs 29.8 kg/m2, P < 0.0001；辅助组2:26.3 kg/m2 vs 29.2 kg/m2, P < 0.0001)， T1D持续时间更长(25.8年vs 21.0年，P < 0.0001；24.1年vs 21.0年，P = 0.04)，持续输注降低每日胰岛素剂量(46.4 U vs 57.3 U, P = 0.01；40.9 U vs 57.4 U, P = 0.12)或多次注射(58.4 U vs 68.5 U, P = 0.006；56.0 U vs 65.8 U, P =.03)， c肽检测不到的参与者比例更高(91.5% vs 81.3%；87.0% vs 84.9%)。当对治疗组进行分析时，利拉鲁肽（而非安慰剂）完成者和非完成者之间只有T1D和c肽的持续时间不同。未完成者的AE率更高。结论：长期存在T1D且基线时c肽水平较低的个体比胰岛素产生残留的个体更有可能因ae /缺乏耐受性而停止辅助利拉鲁肽治疗。无论接受何种治疗，较低的BMI预示着受试者不完成治疗的可能性更大。这些新发现可能与临床实践有关。
Determinants of Liraglutide Treatment Discontinuation in Type 1 Diabetes: A Post Hoc Analysis of ADJUNCT ONE and ADJUNCT TWO Randomized Placebo-Controlled Clinical Studies.
Introduction: Two phase 3 randomized controlled studies (ADJUNCT ONE (Clinicaltrials.gov: NCT01836523), ADJUNCT TWO (Clinicaltrials.gov: NCT02098395)) evaluated liraglutide (1.8, 1.2 or 0.6 mg) vs placebo in participants with type 1 diabetes (T1D) as an adjunct to insulin therapy. This paper aims to improve our understanding of the potential mechanisms leading to premature discontinuation of this treatment regimen.
Methods: Post hoc comparisons were conducted on baseline characteristics and adverse event (AE) rates of participants completing and not completing the ADJUNCT studies due to AEs/lack of tolerance using summary tables and variance analysis.
Results: Non-completers (liraglutide and placebo combined) had lower baseline body mass index (BMI) (ADJUNCT ONE: 27.8 kg/m2 vs 29.8 kg/m2, P < .0001; ADJUNCT TWO: 26.3 kg/m2 vs 29.2 kg/m2, P < .0001), longer duration of T1D (25.8 years vs 21.0 years, P < .0001; 24.1 years vs 21.0 years, P = .04), lower daily insulin doses by continuous infusion (46.4 U vs 57.3 U, P = .01; 40.9 U vs 57.4 U, P = .12) or multiple injections (58.4 U vs 68.5 U, P = .006; 56.0 U vs 65.8 U, P =.03) and a higher proportion of participants with undetectable C-peptide (91.5% vs 81.3%; 87.0% vs 84.9%) compared to completers. When analyzed by treatment group, only duration of T1D and C-peptide differed between completers and non-completers among liraglutide (and not placebo) participants. The AE rates were higher for non-completers.
Conclusion: Individuals with longer-standing T1D and low levels of C-peptide at baseline were more likely to discontinue adjunctive liraglutide treatment due to AEs/lack of tolerance than individuals with residual insulin production. Lower BMI predicted a greater likelihood of non-completion for the included participants, regardless of treatment. These new findings may be relevant for clinical practice.
期刊介绍：
The Journal of Diabetes Science and Technology (JDST) is a bi-monthly, peer-reviewed scientific journal published by the Diabetes Technology Society. JDST covers scientific and clinical aspects of diabetes technology including glucose monitoring, insulin and metabolic peptide delivery, the artificial pancreas, digital health, precision medicine, social media, cybersecurity, software for modeling, physiologic monitoring, technology for managing obesity, and diagnostic tests of glycation. The journal also covers the development and use of mobile applications and wireless communication, as well as bioengineered tools such as MEMS, new biomaterials, and nanotechnology to develop new sensors. Articles in JDST cover both basic research and clinical applications of technologies being developed to help people with diabetes.
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