King Grub
2018-12-21, 12:13
Objective
Leucine was previously demonstrated to allosterically activate mammalian sirtuin 1 and synergize with other sirtuin 1/AMP‐activated protein kinase/nitric oxide pathway activators to modulate energy metabolism. The objective of this study was to evaluate the effects of a triple combination of leucine, metformin, and sildenafil (NS‐0200) on body weight and obesity comorbidities in a phase 2 randomized trial.
Methods
A total of 91 subjects with obesity were randomized to placebo, low dose (1.1 g leucine/0.5 g metformin/0.5 mg sildenafil), or high dose (1.1 g leucine/0.5 g metformin/1.0 mg sildenafil) twice daily for 16 weeks. Seventy subjects completed the trial and met all a priori compliance criteria. Hypertensive (n = 35) and hypertriglyceridemic (n = 22) subcohorts were also analyzed.
Results
NS‐0200 dose‐responsively reduced weight; high dose reduced weight by 2.4 and 5.0 kg in the full and high‐triglyceride cohorts, respectively (P < 0.0001). High‐dose NS‐0200 treatment also decreased blood pressure (−5.5 mm Hg diastolic pressure; P = 0.011), with greater effects among hypertensive subjects. NS‐0200 also significantly reduced triglycerides and hemoglobin A1c. Significant improvement in ≥ 2 comorbidities was exhibited by 54% of subjects in the high‐dose arm versus 5% of placebo subjects (P = 0.0009). Treatment‐emergent adverse events did not significantly differ among groups.
Randomized Controlled Trial of a Leucine‐Metformin‐Sildenafil Combination (NS‐0200) on Weight and Metabolic Parameters. Obesity, 20 December 2018.
https://onlinelibrary.wiley.com/doi/10.1002/oby.22346
Leucine was previously demonstrated to allosterically activate mammalian sirtuin 1 and synergize with other sirtuin 1/AMP‐activated protein kinase/nitric oxide pathway activators to modulate energy metabolism. The objective of this study was to evaluate the effects of a triple combination of leucine, metformin, and sildenafil (NS‐0200) on body weight and obesity comorbidities in a phase 2 randomized trial.
Methods
A total of 91 subjects with obesity were randomized to placebo, low dose (1.1 g leucine/0.5 g metformin/0.5 mg sildenafil), or high dose (1.1 g leucine/0.5 g metformin/1.0 mg sildenafil) twice daily for 16 weeks. Seventy subjects completed the trial and met all a priori compliance criteria. Hypertensive (n = 35) and hypertriglyceridemic (n = 22) subcohorts were also analyzed.
Results
NS‐0200 dose‐responsively reduced weight; high dose reduced weight by 2.4 and 5.0 kg in the full and high‐triglyceride cohorts, respectively (P < 0.0001). High‐dose NS‐0200 treatment also decreased blood pressure (−5.5 mm Hg diastolic pressure; P = 0.011), with greater effects among hypertensive subjects. NS‐0200 also significantly reduced triglycerides and hemoglobin A1c. Significant improvement in ≥ 2 comorbidities was exhibited by 54% of subjects in the high‐dose arm versus 5% of placebo subjects (P = 0.0009). Treatment‐emergent adverse events did not significantly differ among groups.
Randomized Controlled Trial of a Leucine‐Metformin‐Sildenafil Combination (NS‐0200) on Weight and Metabolic Parameters. Obesity, 20 December 2018.
https://onlinelibrary.wiley.com/doi/10.1002/oby.22346