nr-02: Chinese-to-English Response — SOLSTICE Elecoglipron Trial

Task Info

• Module: writing | Discipline: Medicine | Depth: L3 | Verdict: PASS

Source

Aroda et al., The Lancet (2026)

Reviewer Comments (Chinese Input)

• R2.1: 样本量在各剂量组之间分配不均（3:5:3:5:3:3:6:4），应讨论对统计检验力的影响。
• R2.2: 请提供各剂量组胃肠道不良事件的 CTCAE 5.0 详细分级数据，以评估剂量-毒性关系。
• R2.3: 最高剂量组 HbA1c 降幅 1.5 pp 与已获批注射用 GLP-1 受体激动剂（semaglutide 1.0 mg）相比如何？

Response Letter (English Output)

R2.1 — Unequal randomization and statistical power

The randomization ratio (3:5:3:5:3:3:6:4) was designed to allocate more participants to dose groups expected to provide the most informative data while maintaining adequate placebo control. We have added a post hoc power analysis (Supplementary Table S4) showing that all dose groups with n >= 25 achieved power > 0.80 to detect a clinically meaningful difference of 0.5 percentage points versus placebo at alpha = 0.05. We acknowledge the limitation of smaller sample sizes in the 5 mg (n=15) and 10 mg (n=15) groups and have added this caveat to the Discussion.

R2.2 — Gastrointestinal AE grading by dose

We have provided detailed GI adverse event data by CTCAE version 5.0 grade for each dose group in revised Table 3. The dose-toxicity analysis shows: nausea Grade >=2 increased from 8% (5 mg) to 35% (120 mg); vomiting Grade >=2 increased from 3% to 18%. No Grade 4 GI events were observed. Discontinuation due to GI events was <= 5% in all dose groups.

R2.3 — Comparison with injectable GLP-1 RAs

In the SUSTAIN 1 trial, semaglutide 1.0 mg once weekly achieved a placebo-adjusted HbA1c reduction of 1.55 percentage points at week 30 in a similar treatment-naive T2D population. The elecoglipron 120 mg result of approximately 1.5 percentage points at week 26 appears comparable, with the key differentiating factor being oral administration without food or fluid restrictions. Head-to-head comparisons would be required to confirm non-inferiority.

Summary of changes: Power analysis (Table S4), CTCAE 5.0 GI AE grading (Table 3), semaglutide contextual comparison with appropriate caveat (Section 4.2).