One Year's Treatment with the Glucagon-Like Peptide 1 Receptor Agonist Liraglutide Decreases Hepatic Fat Content in Women with Nonalcoholic Fatty Liver Disease and Prior Gestational Diabetes Mellitus in a Randomized, Placebo-Controlled Trial

Louise Vedtofte; Emilie Bahne; Signe Foghsgaard; Jonatan I Bagger; Camilla Andreasen; Charlotte Strandberg; Peter M Gørtz; Jens J Holst; Henning Grønbæk; Jens A Svare; Tine D Clausen; Elisabeth R Mathiesen; Peter Damm; Lise L Gluud; Filip K Knop; Tina Vilsbøll

doi:10.3390/jcm9103213

One Year's Treatment with the Glucagon-Like Peptide 1 Receptor Agonist Liraglutide Decreases Hepatic Fat Content in Women with Nonalcoholic Fatty Liver Disease and Prior Gestational Diabetes Mellitus in a Randomized, Placebo-Controlled Trial

J Clin Med. 2020 Oct 6;9(10):3213. doi: 10.3390/jcm9103213.

Authors

Louise Vedtofte^{1

2}, Emilie Bahne^{1

2}, Signe Foghsgaard^{1

2

3}, Jonatan I Bagger^{1

2}, Camilla Andreasen^{1

2}, Charlotte Strandberg⁴, Peter M Gørtz⁵, Jens J Holst^{6

7}, Henning Grønbæk⁸, Jens A Svare⁹, Tine D Clausen¹⁰, Elisabeth R Mathiesen^{11

12}, Peter Damm^{12

13}, Lise L Gluud^{12

14}, Filip K Knop^{1

2

7

12}, Tina Vilsbøll^{1

2

12}

Affiliations

¹ Steno Diabetes Center Copenhagen, Niels Steensens Vej 2, 2820 Gentofte, Denmark.
² Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Gentofte Hospitalsvej 7, 3rd floor, 2900 Hellerup, Denmark.
³ Danish Diabetes Academy, Odense University Hospital, Kløvervænget 6, Entrance 93, 8th floor, 5000 Odense C, Denmark.
⁴ Department of Radiology, Gentofte Hospital, University of Copenhagen, Gentofte Hospitalsvej 4A, 2900 Hellerup, Denmark.
⁵ Department of Nuclear Medicine, Gentofte Hospital, University of Copenhagen, Gentofte Hospitalsvej 2, 1st floor, 2900 Hellerup, Denmark.
⁶ Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark.
⁷ Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark.
⁸ Department of Hepatology & Gastroenterology, Aarhus University Hospital, University of Aarhus, Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark.
⁹ Department of Obstetrics and Gynaecology, Herlev Hospital, University of Copenhagen, Borgmester Ib Juuls Vej 21, 2730 Herlev, Denmark.
¹⁰ Department of Gynaecology and Obstetrics, Nordsjaellands Hospital, University of Copenhagen, Dyrehavevej 29, 3400 Hillerød, Denmark.
¹¹ Center for Pregnant Women with Diabetes, Department of Endocrinology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark.
¹² Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark.
¹³ Center for Pregnant Women with Diabetes, Department of Obstetrics, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark.
¹⁴ Gastrounit, Hvidovre Hospital, University of Copenhagen, Kettegård Allé 30, 2650 Hvidovre, Denmark.

Abstract

Prior gestational diabetes mellitus (pGDM) is associated with increased risk of nonalcoholic fatty liver disease (NAFLD). Treatment with glucagon-like peptide 1 (GLP-1) receptor agonists has shown beneficial effects in NAFLD patients. We evaluated the effect of the GLP-1 analogue liraglutide on NAFLD features in women with pGDM. Eighty-two overweight/obese, nondiabetic women with pGDM were included. We performed abdominal ultrasound, transient elastography with controlled attenuation parameter (CAP), and blood sampling at baseline and after 1 year. Thirty-seven women were randomized to liraglutide (1.8 mg once-daily) and 45 to placebo. Based on the ultrasound scan, 18 women (22%) had ultrasound-verified NAFLD at baseline and of these, 10 (56%) received liraglutide treatment. After 1 year, eight participants no longer had steatosis, four in each treatment group. The number of participants who developed NAFLD was similar in the two treatment groups; five in the liraglutide group and six in the placebo group (p = 0.74). Compared to placebo, liraglutide reduced the CAP-assessed intrahepatic fat content (-28 (-44;-11) vs. 2 (-13;18) dB/m, p < 0.01) and body weight (-4.7 (-6.4;-2.9) vs. -1.4 (-3;0.3) kg, p < 0.01). One-year's liraglutide treatment had no effect on the presence of ultrasound-diagnosed NAFLD in overweight/obese nondiabetic women with pGDM, but reduced body weight and steatosis assessed by transient elastography with CAP.

Keywords: GLP-1 analogue; GLP-1 receptor agonist; NAFLD; fatty liver; gestational diabetes mellitus; hepatic fat; liraglutide.

Abstract

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