Evaluation of an oral small‐molecule glucagon‐like peptide‐1 receptor agonist, lotiglipron, for type 2 diabetes and obesity: A dose‐ranging, phase 2, randomized, placebo‐controlled study
- terminated early for safety reasons
- Study terminated early for safety reasons after routine data and monitoring review
Authors' conclusion
The efficacy (HbA1c and/or body weight) of a range of lotiglipron doses was demonstrated in T2D and obesity cohorts. The safety profile was largely consistent with what has been previously known about the mechanism of action. Our results are unique in reporting elevations in liver transaminases in a subset of participants treated with lotiglipron, with attempts to identify the at-risk population unsuccessful and therefore clinical development of lotiglipron terminated.
Study context
- Population
- Participants with T2D or obesitytreated with ≥1 dose · Participants with T2D 512 · or obesity 389
- Participants
- 901 participants
- Comparison
- Oral lotiglipron vs placebo
Methodological detailsphase 2, double-blind, placebo-controlled, dose-ranging, Planned analyses modified prior to unblinding
- Phase 2
- Double-blind
- Placebo-controlled
- Dose-ranging
- Planned analyses modified prior to unblinding
Primary result
As reported in the abstract
Lotiglipron 80 mg
−1.44
least squares mean · 90% CI −1.63–-1.26 · %
Placebo
−0.07
least squares mean · 90% CI −0.25–0.11 · %
P < 0.0001
Further findings
| Outcome | Placebo | P value |
|---|---|---|
| Body weight change, obesity cohort · week 20 | −1.84 (90% CI −2.85–-0.83) % | P < 0.01 |
- Body weight change, obesity cohort: Lotiglipron 200 mg, five-step titration −7.47 (90% CI −8.50–-6.43) %
- Body weight change, obesity cohort: decreases across all lotiglipron doses; 200 mg five-step = largest
Safety
Nausea (most common TEAE; GI TEAEs most frequent, mostly mild to moderate)
- T2D cohort: range from placebo to 80 mg
- 4% to 28.8%
- Obesity cohort: range from placebo to 200 mg, four-step titration
- 12.5% to 60.6%
Transaminase elevations
- Lotiglipron, T2D cohort
- 6.6%
- Lotiglipron, obesity cohort
- 6.0%
- Placebo, obesity cohort
- 1.6%
Original publication
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