Combined agonism of nutrient receptors GPR40 and GPR119 with K‐757 and K‐833 results in weight loss and blood pressure reductions in obese subjects without type 2 diabetes mellitus
Authors' conclusion
K-757, alone and in combination with K-833, elicited robust elevations in circulating concentrations of multiple satiety peptides, which elicited some weight loss and blood pressure reductions that suggest potential for metabolic benefit independent of weight loss.
Study context
- Population
- Overweight-obese participants without T2D51–52/arm
- Participants
- 155 participants
- Comparison
- K-757 alone and K-757 + K-833 combination vs placebo
Methodological detailsPhase 2a, double-blind, parallel arm, placebo-controlled, 13-week
- Phase 2a
- Double-blind
- Parallel arm
- Placebo-controlled
- 13-week
Primary result
As reported in the abstract
Placebo-adjusted weight loss · 13 weeks
Placebo-adjusted weight loss
−2.78 %
P < 0.001
K-757 + K-833
Placebo-adjusted weight loss
−1.42 %
P = 0.0756
K-757
Further findings
| Outcome | Placebo-adjusted reduction (mmHg) |
|---|---|
| Placebo-adjusted blood pressure reduction (exploratory endpoint)K-757 + K-833 vs Placebo · blood pressure not elevated at baseline | −6.9/−5.4 |
| Placebo-adjusted blood pressure reduction (exploratory endpoint)K-757 vs Placebo · blood pressure not elevated at baseline | −5.3/−3.2 |
Gut hormone elevations vs placebo with K-757 120 mg BID + K-833 100 mg BID (Phase 1)
- GLP-1
- 3.44×
- Active GLP-1
- 5.06×
- Peptide YY
- 8.63×
- Glucagon dependent insulinotropic peptide
- 1.65×
- Cholecystokinin
- 3.06×
- Oxyntomodulin
- 5.66×
Safety
Adverse events
- Gastrointestinal adverse events (AEs) and discontinuation due to AEs more common in the active treatment arms
- Combination and K-757 alone otherwise well tolerated
Original publication
Combined agonism of nutrient receptors GPR40 and GPR119 with K‐757 and K‐833 results in weight loss and blood pressure reductions in obese subjects without type 2 diabetes mellitus. Diabetes Obes Metab. Published 15 September 2025. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →