Phase 1 (28-day) and Phase 2 (12-week) randomized, double-blind, placebo-controlled, multiple-ascending-dose studies evaluated safety, tolerability, pharmacokinetics, and efficacy (weight loss, appetite, gastric emptying) of TERN-601 — a once-daily oral small-molecule GLP-1 receptor agonist — in adults with obesity or overweight.
In Phase 1, TERN-601 produced dose-dependent, statistically significant weight loss vs. placebo at all doses over 28 days. In Phase 2, doses ≥500 mg led to significantly greater mean % weight loss at Week 12 vs. placebo. GI adverse events were dose-related and class-consistent. Critically, 3 Phase 2 participants had transaminase elevations consistent with potential drug-induced liver injury (DILI), leading to clinical development discontinuation.
- Short follow-up (28 days and 12 weeks); long-term safety and efficacy unknown. - Specific weight-loss magnitudes and participant counts per arm are not reported in the abstract. - Program was discontinued due to liver safety signals, so no data on higher doses or longer durations exist.
TERN-601 has been discontinued due to hepatotoxicity signals (potential DILI in 3 Phase 2 participants); it should not be considered for clinical use. These findings reinforce the need to monitor liver safety closely in trials of novel oral small-molecule GLP-1 receptor agonists.
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