A Randomized Placebo-Controlled Trial of HTD1801 Monotherapy in Participants With Type 2 Diabetes

OBJECTIVE: The safety and efficacy of HTD1801 versus placebo were evaluated in participants with type 2 diabetes inadequately controlled with diet and exercise. RESEARCH DESIGN AND METHODS: Key entry criteria of this phase 3, randomized, placebo-controlled trial included type 2 diabetes (per World Health Organization guidelines), HbA1c 7.0-10.5% (53-91 mmol/mol), fasting plasma glucose ≤13.9 mmol/L, and ≥8 weeks of diet and exercise. Participants were randomized and treated 2:1 to HTD1801 1,000 mg twice daily (BID) (n = 271) or placebo (n = 136). The primary end point was the change from baseline in HbA1c at week 24. After completion of a 24-week, double-blind trial, participants could enter a 28-week open-label extension during which everyone received HTD1801 1,000 mg BID. Safety was assessed for 56 weeks. RESULTS: Baseline HbA1c was 8.5% (69 mmol/mol) in both groups. The primary end point was achieved: HTD1801-treated participants achieved a change in HbA1c of -1.3% versus -0.6% with placebo (least squares mean difference -0.7%; 95% CI -0.8, -0.5; P < 0.0001). After 24 weeks of HTD1801 treatment, significant improvements were observed in key cardiometabolic and inflammatory markers. HbA1c reductions were durable through 52 weeks. The most common adverse events were mild to moderate diarrhea (HTD1801: n = 26 participants [9.6%]; placebo: n = 1 participant [0.7%]); most of which occurred at treatment initiation. Longer-term safety (56 weeks) was consistent with safety findings of the double-blind trial. CONCLUSIONS: HTD1801 treatment produced sustained improvements in glycemic, cardiometabolic, and inflammatory parameters, supporting further evaluation as a well-tolerated oral therapy for patients with type 2 diabetes.

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Journal
Diabetes Care
Published
2026-08-24
DOI
https://doi.org/10.2337/dc26-0739
Primary Topic
Diet and metabolism studies
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article
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article

A Randomized Placebo-Controlled Trial of HTD1801 Monotherapy in Participants With Type 2 Diabetes

Linong Ji, Shuping Zhao, Yunming Gao, L MacConell et al.
Diabetes Care
Diet and metabolism studies
article

A Randomized Placebo-Controlled Trial of HTD1801 Monotherapy in Participants With Type 2 Diabetes

Linong Ji, Shuping Zhao, Yunming Gao, L MacConell, Wenli Sun, Luhua Lai, Xiaojing Wang, Xiaomei Wang, Liping Liu, Adilijiang Abulimiti, Xunhong Wang, Dexue Liu, JIANPING YAO, Kun Wang, Haifang Wang, Xiaowen Chen, Jie Bai, Sihong Wang, Kui Liu, Tingyu Ke, Yibing Lu, Chi Zhang, Yan Liu, Yaoming Xue, Jingna Lin, Hongwei Ling, Min Li, Li Mao, Liujun Fu, Yufeng Li, Yujin Ma, Meng Yu, Hanqing Cai, Xinsheng Li, Lianwei Wang, Jianhua Ma, Guoyue Yuan, Yu Liu, Fang Yu, Yanyan Chen, Dongmei Li, SYMPHONY-1 Investigators:, Junli Xue, Jie Han, Yan Zhu, Linong Ji, Shu Li, Xin Zhang, Xiaohong Jiang, Xiaolin Dong, Zhongjing Wang, Yawei Zhang, Lian Guo, Ye Lei, Jianlin Geng, Zhifeng Cheng, Weigang Zha, Lixin Yang, Yan Bi, Bo Feng, Li Liu, Yan Wu
article en

Abstract

OBJECTIVE: The safety and efficacy of HTD1801 versus placebo were evaluated in participants with type 2 diabetes inadequately controlled with diet and exercise. RESEARCH DESIGN AND METHODS: Key entry criteria of this phase 3, randomized, placebo-controlled trial included type 2 diabetes (per World Health Organization guidelines), HbA1c 7.0-10.5% (53-91 mmol/mol), fasting plasma glucose ≤13.9 mmol/L, and ≥8 weeks of diet and exercise. Participants were randomized and treated 2:1 to HTD1801 1,000 mg twice daily (BID) (n = 271) or placebo (n = 136). The primary end point was the change from baseline in HbA1c at week 24. After completion of a 24-week, double-blind trial, participants could enter a 28-week open-label extension during which everyone received HTD1801 1,000 mg BID. Safety was assessed for 56 weeks. RESULTS: Baseline HbA1c was 8.5% (69 mmol/mol) in both groups. The primary end point was achieved: HTD1801-treated participants achieved a change in HbA1c of -1.3% versus -0.6% with placebo (least squares mean difference -0.7%; 95% CI -0.8, -0.5; P < 0.0001). After 24 weeks of HTD1801 treatment, significant improvements were observed in key cardiometabolic and inflammatory markers. HbA1c reductions were durable through 52 weeks. The most common adverse events were mild to moderate diarrhea (HTD1801: n = 26 participants [9.6%]; placebo: n = 1 participant [0.7%]); most of which occurred at treatment initiation. Longer-term safety (56 weeks) was consistent with safety findings of the double-blind trial. CONCLUSIONS: HTD1801 treatment produced sustained improvements in glycemic, cardiometabolic, and inflammatory parameters, supporting further evaluation as a well-tolerated oral therapy for patients with type 2 diabetes.

Diabetes Care
Yuncheng University (CN), Jiangsu University (CN), Harbin Medical University (CN), Peking University (CN), Affiliated Hospital of Jiangsu University (CN), Beijing Xuanwu Traditional Chinese Medicine Hospital (CN), North China Institute of Aerospace Engineering (CN), Zoucheng People's Hospital (CN), Jiangxi Pingxiang People's Hospital (CN), Fourth Affiliated Hospital of Harbin Medical University (CN), The First People's Hospital of Changde (CN), Peking University People's Hospital (CN), First Affiliated Hospital of Henan University of Science and Technology (CN), Nanyang Medical College (CN), Second Affiliated Hospital of Jilin University (CN), G1 Therapeutics (United States) (US), Celldex Therapeutics (United States) (US), The Sixth People's Hospital of Shenyang (CN), Nanjing Medical University (CN)
Good health and well-being
Openalex Percentile: Top 10%
Diet and metabolism studies
DOISourceOpenAlex
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