Empagliflozin Effectively Lowers Liver Fat... : Diabetes Care (original) (raw)

Nonalcoholic Fatty Liver Disease in Diabetes

Empagliflozin Effectively Lowers Liver Fat Content in Well-Controlled Type 2 Diabetes: A Randomized, Double-Blind, Phase 4, Placebo-Controlled Trial

Sabine Kahl
Sofiya Gancheva
Klaus Straßburger
Christian Herder
Jürgen Machann
Hisayuki Katsuyama
Stefan Kabisch
Elena Henkel
Stefan Kopf
Merit Lagerpusch
Konstantinos Kantartzis
Yuliya Kupriyanova
Daniel Markgraf
Theresa van Gemert
Birgit Knebel
Martin F. Wolkersdorfer
Oliver Kuss
Jong-Hee Hwang
Stefan R. Bornstein
Christian Kasperk
Norbert Stefan
Andreas Pfeiffer
Andreas L. Birkenfeld
Michael Roden

Diabetes Care

(

)

298

305

February 2020

| DOI: 10.2337/dc19-0641

OBJECTIVE

To evaluate whether the sodium-glucose cotransporter 2 inhibitor empagliflozin (EMPA) reduces liver fat content (LFC) in recent-onset and metabolically well-controlled type 2 diabetes (T2D).

RESEARCH DESIGN AND METHODS

Patients with T2D (n = 84) (HbA1c 6.6 ± 0.5% [49 ± 10 mmol/mol], known disease duration 39 ± 27 months) were randomly assigned to 24 weeks of treatment with 25 mg daily EMPA or placebo. The primary end point was the difference of the change in LFC as measured with magnetic resonance methods from 0 (baseline) to 24 weeks between groups. Tissue-specific insulin sensitivity (secondary outcome) was assessed by two-step clamps using an isotope dilution technique. Exploratory analysis comprised circulating surrogate markers of insulin sensitivity and liver function. Statistical comparison was done by ANCOVA adjusted for respective baseline values, age, sex, and BMI.

RESULTS

EMPA treatment resulted in a placebo-corrected absolute change of −1.8% (95% CI −3.4, −0.2; P = 0.02) and relative change in LFC of −22% (−36, −7; P = 0.009) from baseline to end of treatment, corresponding to a 2.3-fold greater reduction. Weight loss occurred only with EMPA (placebo-corrected change −2.5 kg [−3.7, −1.4]; P < 0.001), while no placebo-corrected change in tissue-specific insulin sensitivity was observed. EMPA treatment also led to placebo-corrected changes in uric acid (−74 mol/L [−108, −42]; P < 0.001) and high-molecular-weight adiponectin (36% [16, 60]; P < 0.001) levels from 0 to 24 weeks.

CONCLUSIONS

EMPA effectively reduces hepatic fat in patients with T2D with excellent glycemic control and short known disease duration. Interestingly, EMPA also decreases circulating uric acid and raises adiponectin levels despite unchanged insulin sensitivity. EMPA could therefore contribute to the early treatment of nonalcoholic fatty liver disease in T2D.