Randomized Controlled Trial of a Leucine-Metformin-Sildenafil Combination (NS-0200) on Weight and Metabolic Parameters

Michael B. Zemel, Orville Kolterman, Mary Rinella, Raj Vuppalanchi, Omar Flores, A. Sidney Barritt, Mohammad Siddiqui, Naga Chalasani

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)59-67
Number of pages9
JournalObesity
Volume27
Issue number1
DOIs
StatePublished - Jan 1 2019

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Metformin
Leucine
Randomized Controlled Trials
Sirtuin 1
Comorbidity
Weights and Measures
Obesity
Triglycerides
Placebos
Blood Pressure
AMP-Activated Protein Kinases
Energy Metabolism
Compliance
Nitric Oxide
Hemoglobins
Therapeutics
Body Weight
Sildenafil Citrate

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Nutrition and Dietetics

Cite this

Randomized Controlled Trial of a Leucine-Metformin-Sildenafil Combination (NS-0200) on Weight and Metabolic Parameters. / Zemel, Michael B.; Kolterman, Orville; Rinella, Mary; Vuppalanchi, Raj; Flores, Omar; Barritt, A. Sidney; Siddiqui, Mohammad; Chalasani, Naga.

In: Obesity, Vol. 27, No. 1, 01.01.2019, p. 59-67.

Research output: Contribution to journalArticle

Zemel, Michael B. ; Kolterman, Orville ; Rinella, Mary ; Vuppalanchi, Raj ; Flores, Omar ; Barritt, A. Sidney ; Siddiqui, Mohammad ; Chalasani, Naga. / Randomized Controlled Trial of a Leucine-Metformin-Sildenafil Combination (NS-0200) on Weight and Metabolic Parameters. In: Obesity. 2019 ; Vol. 27, No. 1. pp. 59-67.
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