Randomized Controlled Trial of a Leucine‐Metformin‐Sildenafil Combination (NS‐0200) on Weight and Metabolic Parameters
Open accessAbstract
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. Conclusions: These data support further study of NS‐0200 as a therapy for obesity and associated comorbidities.
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A phase 2 RCT demonstrated that body weight was significantly reduced in overweight or obese patients with BMI 25-40 kg/m2 (n=32) receiving a fixed-dose combination of leucine 1.1 g, metformin 0.5 g, and sildenafil 1.0 mg for 16 weeks.
“A phase 2 RCTs demonstrated that body weight was significantly reduced in overweight or obese patients with a BMI ranging from 25 to 40 kg/m2 (n = 32) to receive a fixed-dose combination of leucine 1.1 g, metformin 0.5 g, and sildenafil 1.0 mg for 16 weeks [110].”
From Long-Term Efficacy and Safety of Anti-Obesity Treatment: Where Do We Stand? (2021) · cites this paper as [110]
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- Authors
- Zemel, M. B., Kolterman, O., Rinella, M., Vuppalanchi, R., Flores, O., Barritt, A. S., Siddiqui, M., & Chalasani, N.
- Affiliations
- Tennessee Department of Transportation (US)
- Northwestern University (US)
- Indiana University Indianapolis (US)
- University of North Carolina at Chapel Hill (US)
- Virginia Commonwealth University (US)
- Corresponding author
- Zemel, Michael B.
- Chalasani, Naga
- ORCID
- Venue
- Obesity
- Publisher
- Wiley
- Published
- 2018-12-20
- Volume
- 27
- Issue
- 1
- Pages
- 59-67
- ISSN
- 1930-7381 (ISSN-L)
- 1930-739X
- OpenAlex
- W2906555725
- Cited by
- 19
- References
- 46
- Citations by year
- 2024: 1 · 2023: 5 · 2022: 3 · 2021: 2 · 2020: 6 · 2019: 2
- FWCI
- 1.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Obesity (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Northwestern University
- Virginia Commonwealth University
- University of North Carolina at Chapel Hill
- University of California, San Diego
- Topics
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- leucine, metformin, sildenafil, weight loss, hypertension, hypertriglyceridemia, SIRT1, AMPK, nitric oxide pathway, energy metabolism, blood pressure, triglycerides, glycemic control, comorbidities
- MeSH terms
- Sildenafil Citrate, Body Weight, Double-Blind Method, Female, Humans, Hypoglycemic Agents, Leucine, Male, Metformin, Middle Aged, Obesity, Phosphodiesterase 5 Inhibitors
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