Thomas Damgaard Sandahl

Randomised clinical study: acute effects of metformin versus placebo on portal pressure in patients with cirrhosis and portal hypertension

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Randomised clinical study: acute effects of metformin versus placebo on portal pressure in patients with cirrhosis and portal hypertension. / Rittig, Nikolaj; Aagaard, Niels Kristian; Villadsen, Gerda Elisabeth; Sandahl, Thomas Damgaard; Jessen, Niels; Grønbaek, Henning; George, Jacob.

In: Alimentary Pharmacology and Therapeutics, Vol. 54, No. 3, 08.2021, p. 320-328.

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@article{6e73e0e8cf644cde9d48a0da7646310e,
title = "Randomised clinical study:: acute effects of metformin versus placebo on portal pressure in patients with cirrhosis and portal hypertension",
abstract = "BACKGROUND: Portal hypertension is the main determinant of clinical decompensation in patients with liver cirrhosis. In preclinical data metformin lowers portal pressure, but there are no clinical data for this beneficial effect.AIMS: To investigate the acute effects of metformin on hepatic venous pressure gradient (HVPG) and liver perfusion.METHODS: In a randomised, double-blinded study design, we investigated 32 patients with cirrhosis before and 90 minutes after ingestion of 1000-mg metformin (n = 16) or placebo (n = 16). Liver vein catherisation was performed to evaluate HVPG and indocyanine green (ICG) infusion for investigation of hepatic blood flow.RESULTS: The mean relative change in HVPG was -16% (95% CI: -28% to -4%) in the metformin group compared with 4% (95% CI: -6% to 14%) in the placebo group (time × group interaction, P = 0.008). In patients with baseline HVPG ≥12 mm Hg clinically significant improvements in HVPG (HVPG <12 mm Hg or a >20% reduction in HVPG) were observed in 46% (6/13) of metformin-treated and in 8% (1/13) of placebo-treated patients (P = 0.07). There were no changes or differences in systemic blood pressure, heart rate, hepatic plasma and blood flow, hepatic ICG clearance, hepatic O2 uptake or inflammation markers between groups.CONCLUSIONS: A single oral metformin dose acutely reduces HVPG in patients with portal hypertension without affecting systemic or liver hemodynamics or inflammatory biomarkers. This offers a promising perspective of a safe and inexpensive treatment option that should be investigated in larger-scale clinical studies with long-term outcomes in patients with cirrhosis and portal hypertension.",
keywords = "ACUTE HEMODYNAMIC-RESPONSE, COMPLICATIONS, INDOCYANINE GREEN, LIVER, OUTCOMES, PATHOPHYSIOLOGY, PREVENTION, PROPRANOLOL, REDUCTION, RESISTANCE, Hypertension, Portal/drug therapy, Humans, Liver Cirrhosis/drug therapy, Metformin/therapeutic use, Portal Pressure",
author = "Nikolaj Rittig and Aagaard, {Niels Kristian} and Villadsen, {Gerda Elisabeth} and Sandahl, {Thomas Damgaard} and Niels Jessen and Henning Gr{\o}nbaek and Jacob George",
note = "{\textcopyright} 2021 John Wiley & Sons Ltd.",
year = "2021",
month = aug,
doi = "10.1111/apt.16460",
language = "English",
volume = "54",
pages = "320--328",
journal = "Alimentary Pharmacology and Therapeutics",
issn = "0269-2813",
publisher = "Wiley-Blackwell Publishing Ltd.",
number = "3",

}

RIS

TY - JOUR

T1 - Randomised clinical study:

T2 - acute effects of metformin versus placebo on portal pressure in patients with cirrhosis and portal hypertension

AU - Rittig, Nikolaj

AU - Aagaard, Niels Kristian

AU - Villadsen, Gerda Elisabeth

AU - Sandahl, Thomas Damgaard

AU - Jessen, Niels

AU - Grønbaek, Henning

AU - George, Jacob

N1 - © 2021 John Wiley & Sons Ltd.

PY - 2021/8

Y1 - 2021/8

N2 - BACKGROUND: Portal hypertension is the main determinant of clinical decompensation in patients with liver cirrhosis. In preclinical data metformin lowers portal pressure, but there are no clinical data for this beneficial effect.AIMS: To investigate the acute effects of metformin on hepatic venous pressure gradient (HVPG) and liver perfusion.METHODS: In a randomised, double-blinded study design, we investigated 32 patients with cirrhosis before and 90 minutes after ingestion of 1000-mg metformin (n = 16) or placebo (n = 16). Liver vein catherisation was performed to evaluate HVPG and indocyanine green (ICG) infusion for investigation of hepatic blood flow.RESULTS: The mean relative change in HVPG was -16% (95% CI: -28% to -4%) in the metformin group compared with 4% (95% CI: -6% to 14%) in the placebo group (time × group interaction, P = 0.008). In patients with baseline HVPG ≥12 mm Hg clinically significant improvements in HVPG (HVPG <12 mm Hg or a >20% reduction in HVPG) were observed in 46% (6/13) of metformin-treated and in 8% (1/13) of placebo-treated patients (P = 0.07). There were no changes or differences in systemic blood pressure, heart rate, hepatic plasma and blood flow, hepatic ICG clearance, hepatic O2 uptake or inflammation markers between groups.CONCLUSIONS: A single oral metformin dose acutely reduces HVPG in patients with portal hypertension without affecting systemic or liver hemodynamics or inflammatory biomarkers. This offers a promising perspective of a safe and inexpensive treatment option that should be investigated in larger-scale clinical studies with long-term outcomes in patients with cirrhosis and portal hypertension.

AB - BACKGROUND: Portal hypertension is the main determinant of clinical decompensation in patients with liver cirrhosis. In preclinical data metformin lowers portal pressure, but there are no clinical data for this beneficial effect.AIMS: To investigate the acute effects of metformin on hepatic venous pressure gradient (HVPG) and liver perfusion.METHODS: In a randomised, double-blinded study design, we investigated 32 patients with cirrhosis before and 90 minutes after ingestion of 1000-mg metformin (n = 16) or placebo (n = 16). Liver vein catherisation was performed to evaluate HVPG and indocyanine green (ICG) infusion for investigation of hepatic blood flow.RESULTS: The mean relative change in HVPG was -16% (95% CI: -28% to -4%) in the metformin group compared with 4% (95% CI: -6% to 14%) in the placebo group (time × group interaction, P = 0.008). In patients with baseline HVPG ≥12 mm Hg clinically significant improvements in HVPG (HVPG <12 mm Hg or a >20% reduction in HVPG) were observed in 46% (6/13) of metformin-treated and in 8% (1/13) of placebo-treated patients (P = 0.07). There were no changes or differences in systemic blood pressure, heart rate, hepatic plasma and blood flow, hepatic ICG clearance, hepatic O2 uptake or inflammation markers between groups.CONCLUSIONS: A single oral metformin dose acutely reduces HVPG in patients with portal hypertension without affecting systemic or liver hemodynamics or inflammatory biomarkers. This offers a promising perspective of a safe and inexpensive treatment option that should be investigated in larger-scale clinical studies with long-term outcomes in patients with cirrhosis and portal hypertension.

KW - ACUTE HEMODYNAMIC-RESPONSE

KW - COMPLICATIONS

KW - INDOCYANINE GREEN

KW - LIVER

KW - OUTCOMES

KW - PATHOPHYSIOLOGY

KW - PREVENTION

KW - PROPRANOLOL

KW - REDUCTION

KW - RESISTANCE

KW - Hypertension, Portal/drug therapy

KW - Humans

KW - Liver Cirrhosis/drug therapy

KW - Metformin/therapeutic use

KW - Portal Pressure

U2 - 10.1111/apt.16460

DO - 10.1111/apt.16460

M3 - Journal article

C2 - 34165199

VL - 54

SP - 320

EP - 328

JO - Alimentary Pharmacology and Therapeutics

JF - Alimentary Pharmacology and Therapeutics

SN - 0269-2813

IS - 3

ER -