Evidence mapPaperPMID 39008234Full record

ArticleDiabetes therapy : research, treatment and education of diabetes and related disorders2024

ISIS 449884 Injection Add-On to Metformin in Patients with Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled, Phase II Clinical Study.

Linong Ji, Leili Gao, Zhikai Feng, Guoliang Chen, Jing Fu, Erin Morgan, Sanjay Bhanot, Shan Gao, Hongyan Zhang, Zicai Liang and 1 more

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Article in Diabetes therapy : research, treatment and education of diabetes and related disorders, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Not yet cited in PubMed.

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2 · The registry

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4 · The record

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5 · Who and what money

Authors and funding

11 authors.

Linong Ji *Department of Endocrinology and Metabolism, Peking University People's Hospital, No. 11 Xi zhi men South Street, Xicheng District, Beijing, 100044, China. jiln@bjmu.edu.cn.
Leili Gao *Department of Endocrinology and Metabolism, Peking University People's Hospital, No. 11 Xi zhi men South Street, Xicheng District, Beijing, 100044, China.
Zhikai FengRibo Life Science Co Ltd, Suzhou, Jiangsu, China.
Guoliang ChenRibo Life Science Co Ltd, Suzhou, Jiangsu, China.
Jing FuRibo Life Science Co Ltd, Suzhou, Jiangsu, China.
Erin MorganIonis Pharmaceuticals, Carlsbad, CA, USA.
Sanjay BhanotIonis Pharmaceuticals, Carlsbad, CA, USA.
Shan GaoRibo Life Science Co Ltd, Suzhou, Jiangsu, China.
Hongyan ZhangRibo Life Science Co Ltd, Suzhou, Jiangsu, China.
Zicai LiangRibo Life Science Co Ltd, Suzhou, Jiangsu, China.
Li-Ming GanRibo Life Science Co Ltd, Suzhou, Jiangsu, China. li-ming.gan@ribocure.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionISIS 449884, a 2'-O-methoxyethyl antisense oligonucleotide that targets the glucagon receptor (GCGR), has demonstrated an ability to reduce hepatic glucose output and lower the blood glucose level. The primary objective of this study was to investigate the safety and efficacy of ISIS 449884 as an add-on to metformin in a population of Chinese patients with type 2 diabetes mellitus (T2DM).

methodThis was a multicenter, placebo-controlled (2:1), randomized, double-blind, parallel-enrollment, multiple-dose phase II study in Chinese patients with T2DM. A total of 90 patients who were uncontrolled by stable metformin monotherapy were randomized into three cohorts. Thirty subjects were enrolled in each cohort and received injections of ISIS 449884 (50 mg or 60 mg weekly or 100 mg every other week) or a corresponding volume of placebo (0.25 mL and 0.3 mL weekly or 0.5 mL every other week) subcutaneously in a 2:1 ratio for 16 weeks.

resultsThe primary efficacy endpoint was analyzed in 88 subjects (ISIS 449884, n = 59; placebo, n = 29). The corrected LS mean change from baseline in glycated hemoglobin (HbA1c) at week 17 in the pooled ISIS 449884 treatment group was - 1.31% (95% CI - 1.66%, - 0.96%), and that in the pooled placebo group was 0.15% (95% CI - 0.37%, 0.66%). The LS mean difference between the two groups was - 1.46% (95% CI - 1.92%, - 1.00%, P < 0.001). Treatment-emergent adverse events (TEAEs) occurred in 53/60 subjects (88.3%) and 25/30 subjects (83.3%) in the pooled ISIS 449884 treatment group and the pooled placebo group, respectively, with similar incidences. Drug-related TEAEs occurred in 41/60 subjects (68.3%) and 9/30 subjects (30.0%), respectively. TEAEs of grade 3 or higher occurred in 5/60 (8.3%) subjects and 2/30 (6.7%) subjects, respectively, and none of them were drug related.

conclusionsThe ISIS 449884 injection add-on to metformin significantly reduced HbA1c in patients with T2DM uncontrolled by stable metformin monotherapy and showed an acceptable benefit/risk profile. CLINICAL

trial registrationwww.chinadrugtrials.org.cn , CTR20191096.

Indexed as

Glucagon receptorISIS 449884MetforminType 2 diabetes mellitus

Identifiers

PMID39008234
PMCPMC11410740

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.