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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. [ABSTRACT FROM AUTHOR]

Previous studies suggest that a low-glycaemic index (LGI) diet may improve insulin sensitivity (IS). As IS has been shown to decrease during refeeding, we hypothesised that an LGI- v. high-GI (HGI) diet might have favourable effects during this phase. In a controlled nutritional intervention study, sixteen healthy men (aged 26·8 (sd 4·1) years, BMI 23·0 (sd 1·7) kg/m2) followed 1 week of overfeeding, 3 weeks of energy restriction and of 2 weeks refeeding at ± 50 % energy requirement (50 % carbohydrates, 35 % fat and 15 % protein). During refeeding, subjects were divided into two matched groups receiving either high-fibre LGI or lower-fibre HGI foods (GI 40 v. 74, fibre intake 65 (sd 6) v. 27 (sd 4) g/d). Body weight was equally regained in both groups with refeeding (mean regain 70·5 (sd 28·0) % of loss). IS was improved by energy restriction and decreased with refeeding. The decreases in IS were greater in the HGI than in the LGI group (group × time interactions for insulin, homeostasis model assessment of insulin resistance (HOMAIR), Matsuda IS index (MatsudaISI); all P< 0·05). Mean interstitial glucose profiles during the day were also higher in the HGI group (ΔAUCHGI-LGI of continuous interstitial glucose monitoring: 6·6 mmol/l per 14 h, P= 0·04). At the end of refeeding, parameters of IS did not differ from baseline values in either diet group (adiponectin, insulin, HOMAIR, MatsudaISI, M-value; all P>0·05). In conclusion, nutritional stress imposed by dietary restriction and refeeding reveals a GI/fibre effect in healthy non-obese subjects. LGI foods rich in fibre may improve glucose metabolism during the vulnerable refeeding phase of a weight cycle. [ABSTRACT FROM PUBLISHER]