Leucine + metformin + sildenafil
Leucine + metformin + sildenafil has been studied in 3 papers since 2016: 2 trials in people, 1 in animals. The newest paper, Dec 20, 2018: “Randomized Controlled Trial of a Leucine-Metformin-Sildenafil Combination (NS-0200) on Weight and Metabolic Parameters”.
See all 3 papers on leucine + metformin + sildenafil
At a glance
The findings reach people, from one lab or study. 2 independent labs in 2 countries.
“high dose reduced weight by 2.4 and 5.0 kg in the full and high-triglyceride cohorts, respectively (P < 0.0001)”
1 of its findings points the other way.
- 2 independent labs in 2 countries
- 1 finding against
- Funders: NuSirt Biopharma and 4 more
- 9 of 14 findings with company ties
- Human trial2
- Animals1
Studies in people
2 studies gave leucine + metformin + sildenafil to people and measured what changed.
| What changed | Design | People | Source |
|---|---|---|---|
down: Decreases body weight-2.4 kg full cohort; -5.0 kg high-triglyceride cohort down: Decreases diastolic blood pressure-5.5 mm Hg diastolic pressure up: Improves obesity comorbidities54% high-dose vs 5% placebo | Randomized trial16 weeks | 91 peopleHigh-dose arm; full cohort (2.4 kg) and high-triglyceride cohort (5.0 kg) | Obesity (Silver Spring, Md.), Dec 20, 2018 |
down: Decreases hepatic fat15.7% reduction from baseline (relative change) no change: Has no effect on hepatic fat down: Decreases metabolically active lipids | Randomized trial16 weeks | 35 peopleHigh-dose; subgroup with ALT above median (50 U/L) | Alimentary pharmacology & therapeutics, Apr 25, 2018 |
What did studies of leucine + metformin + sildenafil find?
11Studies of leucine + metformin + sildenafil measured 11 outcomes, among them triglyceride, fatty acid β-oxidation and hepatic fat.
Triglyceride
downin humans1downin mice1
2 studies
Triglyceride
downin humans1downin mice1
Leucine + metformin + sildenafil decreases triglyceride in humans.
“NS-0200 also significantly reduced triglycerides and hemoglobin A1c.”
Human trialNS-020016 weeks
Obesity (Silver Spring, Md.)
Leucine + metformin + sildenafil decreases triglyceride in mice (atherogenic diet-induced NASH).
“Sild-Met-Leu reduced the diet induced increases of ALT, TGFβ, PAI-1, IL1β, and TNFα, hepatic collagen expression, and nearly completely reversed hepatocyte ballooning and triglyceride accumulation”
Animalsatherogenic diet-induced NASHliver
International journal of hepatology
Fatty acid β-oxidation
upin humans1upin mouse cells1
2 studies
Fatty acid β-oxidation
upin humans1upin mouse cells1
Leucine + metformin + sildenafil increases fatty acid β-oxidation in humans (dose-responsive; overall and high ALT cohorts).
“and up-regulation of fatty acid oxidation”
Human trialdose-responsive; overall and high ALT cohortstriple combination16 weeks
Alimentary pharmacology & therapeutics
Leucine + metformin + sildenafil increases fatty acid β-oxidation in mouse cells.
“The three-way combination Sild-Met-Leu increased hepatic fatty acid oxidation and reduced lipogenic gene expression and inflammatory marker in vitro.”
Cellsliver cells and macrophages
International journal of hepatology
Hepatic fat
no changein humans1downin humans1−16% reduction from baseline (relative change
1 study
Hepatic fat
no changein humans1downin humans1−16% reduction from baseline (relative change
Leucine + metformin + sildenafil showed no clear effect on hepatic fat in humans (full cohort).
“In the full cohort, active treatments did not separate from placebo.”
Human trialfull cohorttriple combinationliver16 weeks
Alimentary pharmacology & therapeutics
Leucine + metformin + sildenafil decreases hepatic fat in humans (high-dose; subgroup with ALT above median (50 U/L)) (15.7% reduction from baseline (relative change)).
“High dose NS-0200 reduced hepatic fat by 15.7% (relative change from baseline) in the high ALT group (P < 0.005)”
Human trialhigh-dose; subgroup with ALT above median (50 U/L)triple combinationliver1.0 mg sildenafil with 1.1 g leucine and 0.5 g metformin, twice daily16 weeksn = 35
Alimentary pharmacology & therapeutics
Treatment-emergent adverse events
no changein humans1
1 study
Treatment-emergent adverse events
no changein humans1
Leucine + metformin + sildenafil showed no clear effect on treatment-emergent adverse events in humans.
“Treatment-emergent adverse events did not significantly differ among groups.”
Human trialNS-020016 weeks
Obesity (Silver Spring, Md.)
Obesity comorbidities
upin humans1
1 study
Obesity comorbidities
upin humans1
Leucine + metformin + sildenafil improves obesity comorbidities in humans (proportion of subjects with improvement in 2 or more comorbidities) (54% high-dose vs 5% placebo).
“Significant improvement in ≥ 2 comorbidities was exhibited by 54% of subjects in the high-dose arm versus 5% of placebo subjects (P = 0.0009).”
Human trialproportion of subjects with improvement in 2 or more comorbiditiesNS-0200 high dose1.1 g leucine/0.5 g metformin/1.0 mg sildenafil twice daily16 weeks
Obesity (Silver Spring, Md.)
Diastolic blood pressure
downin humans1
1 study
Diastolic blood pressure
downin humans1
Leucine + metformin + sildenafil decreases diastolic blood pressure in humans (high-dose arm; greater effects among hypertensive subjects) (-5.5 mm Hg diastolic pressure).
“High-dose NS-0200 treatment also decreased blood pressure (-5.5 mm Hg diastolic pressure; P = 0.011)”
Human trialhigh-dose arm; greater effects among hypertensive subjectsNS-0200 high dose1.1 g leucine/0.5 g metformin/1.0 mg sildenafil twice daily16 weeks
Obesity (Silver Spring, Md.)
Body weight
downin humans1
1 study
Body weight
downin humans1
Leucine + metformin + sildenafil decreases body weight in humans (high-dose arm; full cohort (2.4 kg) and high-triglyceride cohort (5.0 kg)) (-2.4 kg full cohort; -5.0 kg high-triglyceride cohort).
“high dose reduced weight by 2.4 and 5.0 kg in the full and high-triglyceride cohorts, respectively (P < 0.0001)”
Human trialhigh-dose arm; full cohort (2.4 kg) and high-triglyceride cohort (5.0 kg)NS-0200 high dose1.1 g leucine/0.5 g metformin/1.0 mg sildenafil twice daily16 weeks
Obesity (Silver Spring, Md.)
Metabolically active lipids
downin humans1
1 study
Metabolically active lipids
downin humans1
Leucine + metformin + sildenafil decreases metabolically active lipids in humans (dose-responsive; overall and high ALT cohorts).
“with significant decreases in metabolically active lipids and up-regulation of fatty acid oxidation”
Human trialdose-responsive; overall and high ALT cohortstriple combination16 weeks
Alimentary pharmacology & therapeutics
Hepatic collagen expression
downin mice1
1 study
Hepatic collagen expression
downin mice1
Leucine + metformin + sildenafil decreases hepatic collagen expression in mice (atherogenic diet-induced NASH).
“hepatic collagen expression, and nearly completely reversed hepatocyte ballooning and triglyceride accumulation, while all two-way combinations had only modest effects”
Animalsatherogenic diet-induced NASHliver
International journal of hepatology
Alanine aminotransferase
downin mice1
1 study
Alanine aminotransferase
downin mice1
Leucine + metformin + sildenafil decreases alanine aminotransferase in mice (atherogenic diet-induced NASH).
“Sild-Met-Leu reduced the diet induced increases of ALT, TGFβ, PAI-1, IL1β, and TNFα, hepatic collagen expression”
Animalsatherogenic diet-induced NASHliver
International journal of hepatology