| Blai et al.[@424559] |
Phase 1b/2a Study |
Phase 1b: 24 HOV
Phase 2a: 54 T2DM and 40 HOV |
Phase 1b: GSBR-1290 (5-90mg) and its effects on body weight (BW) were investigated in 24 HOV over 4 weeks.
Phase 2a: GSBR-1290 on safety, tolerability, HbA1c, glucose, and BW were investigated in 54 participants with T2DM (45 and 90mg) over 12 weeks and in an interim 8-week analysis of 40 HOV (120mg) |
BW was significantly reduced (up to 4.9% placebo-adjusted, p=0.013) over 4 weeks. Most AE were mild to moderate; no discontinuation due to AEs.
Phase 2a T2DM: Placebo-adjusted HbA1c (45 mg: -1.01%, p=0.008; 90 mg: -1.02%, p=0.001), BW (45 mg: -3.51%, p=0.0019; 90 mg: -3.26%, p=0.0013), and plasma glucose (45 mg: -2.70, p=0.01; 90 mg: -2.50, p=0.0008) were significantly reduced at day 84
Phase 2a obesity: Placebo-adjusted BW decreased though day 56 (120 mg: -4.74%; p<0.0001). Well tolerated, AEs were mild-moderate and GI-related, with no SAEs |
| Amin et al.[@424560] |
Phase 2 RCT |
901 participants (T2DM cohort: n = 512, obesity cohort: n = 389) |
T2DM cohort: Lotiglipron QD at one of five maintenance doses (20, 40, 80, 160 or 260 mg) or matching placebo, or semaglutide daily at one maintenance dose (14 mg)
Obesity cohort: Lotiglipron QD at one of four maintenance
doses, with two dose titration regimens for the 200-mg dose (80 mg,140 mg, 200 mg five-step titration, 200 mg four-step titration and 260 mg) or matching placebo. |
T2DM cohort: Reductions in HbA1c were observed across all lotiglipron doses at week 16 (p < 0.0001), with least mean decrease up to -1.44% (90% confidence interval [CI]: -1.63, -1.26) (lotiglipron 80 mg), versus placebo, -0.07% (90% CI: -0.25, 0.11)
Obesity cohort: Decreases in body weight were observed across all lotiglipron doses at week 20 (p < 0.01), up to -7.47% (90% CI: -8.50, -6.43) (lotiglipron 200 mg, five-step titration), versus placebo, -1.84% (90% CI: -2.85, -0.83)
Transaminase elevations were observed in a TDM (6.6%) and obesity cohorts (6%).
Clinical development terminated due to concerns for hepatotoxicity |