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Insulin therapy reduces liver fat burden in type 2 diabetes
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Treatment with Lantus reduced total liver fat burden for patients with type 2 diabetes, according to research published in Diabetes Care.
Additionally, Victoza therapy did not significantly affect liver fat biomarkers. Reduction in liver fat fraction and glycemic control did not differ significantly between Lantus (insulin glargine recombinant, Sanofi Aventis) and Victoza (liraglutide, Novo Nordisk).
An Tang, MD, MSc, of Centre hospitalier de l’Université de Montréal, in Québec, Canada, and colleagues from other institutions enrolled 35 patients with type 2 diabetes whose glycemia was not well-controlled with metformin alone or in combination with other oral agents. Participants were randomly assigned to receive 12 weeks of therapy with either insulin glargine or liraglutide and were examined in the clinic 1 week before beginning treatment, at baseline to begin treatment, and then at 1-month intervals for five more visits.
An Tang
Liver fat burden was assessed by measuring liver proton density fat fraction (PDFF) with magnetic resonance spectroscopy (MRS); MRI was used to measure mean liver PDFF, total liver volume and total liver fat index.
At 12 weeks, the insulin group demonstrated a trend toward a reduction in PDFF measured by MRS (12.6% to 9.9%; P = .06). MRI assessments showed a significant reduction in PDFF (13.8% to 10.6%; P = .005), liver volume (2,010.6 to 1,858.7 mL; P = .01) and total liver fat index (304.4 vs. 209.3% per mL; P = .01). Liver metrics were unchanged in the liraglutide group. HbA1c improved significantly in both treatment groups: for insulin glargine 7.9% to 7.2% (62.5 to 55.2 mmol/mol; P = .005); for liraglutide 7.6% to 6.7% (59.8 to 50.2 mmol/mol; P < .001).
“The administration of insulin glargine therapy may reduce the liver fat burden in patients with type 2 diabetes mellitus, despite a stable body weight and body mass index observed in this treatment arm,”” Tang told Endocrine Today. “Magnetic resonance-based techniques were used as noninvasive biomarkers of liver fat in this trial because repeated liver biopsies would not have been acceptable for these patients with type 2 diabetes who were otherwise not known for chronic liver disease.” – by Jill Rollet
For more information:
An Tang, MD, MSc, can be reached at Tour Viger, 900 rue Saint-Denis, bureau R12.480, Centre de recherche du CHUM, Montréal Québec H2X 0A9, Canada; email: an.tang@umontreal.ca.
Disclosure: Tang reports speaker honoraria from Siemens Medical and Boehringer Ingelheim. He is on the scientific advisory board of Imagia. Please see the full study for a list of all other authors’ relevant financial disclosures.
Perspective
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Kenneth Cusi, MD, FACP, FACE
Tang and colleagues tackle the important issue of treatment choice for patients with type 2 diabetes and nonalcoholic fatty liver disease (NAFLD), a problem that affects the majority of patients with type 2 diabetes and even 50% of those with normal liver enzymes. Its more severe form with stetatohepatitis, NASH, is more common and often progressive in diabetes and may lead to cirrhosis and/or hepatocellular carcinoma, as well as cardiovascular disease. The authors reported that while achieving a similar reduction in fasting plasma glucose and HbA1c, there was a contrast between groups on the effect of treatment on liver fat: a 24% decrease in whole-liver fat and a small 9% reduction in liver volume with insulin glargine, compared with no change with liraglutide.
This work is provocative and much needed to determine the best pharmacologic treatment for patients with uncontrolled type 2 diabetes and NAFLD. Still, the clinical significance of the study is hampered by the small sample size, short follow-up, low-dose of liraglutide used and a significant drop-out in the liraglutide arm (4/18). The increase in plasma triglyceride concentration with insulin and the lack of any effect to decrease liver fat with an incretin mimetic are both discordant with prior studies. Other studies with exenatide and my own experience suggest that incretin mimetics have a moderate but significant effect in reducing liver fat accumulation. I look forward to results of a randomized controlled trial of liraglutide in patients with biopsy-proven NASH that Thompson and colleagues will report at the European Association for the Study of the Liver at the end of April.
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