Empagliflozin Improves Liver Steatosis and Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease and Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Chehrehgosha, Haleh; Sohrabi, Masoudreza; Ismail‐Beigi, Faramarz; Malek, Mojtaba; Babaei, Mohammad Reza; Zamani, Farhad; Ajdarkosh, Hossein; Khoonsari, Mahmoodreza; Fallah, A.; Hosseinkhan, Nazanin

doi:10.1007/s13300-021-01011-3

Cited by 101 publications

(123 citation statements)

References 80 publications

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“…There was a significant decrease in HBA1c, FBS, and PPBS in the present study; the mean differences were 0.6, 32.88, and 64.83 respectively (p=0.000). A similar study by Chehrehgosha et al also showed a significant drop in HbA1c, FBS, and PPBS (p<0.001) [ 16 ]. A study by Kuchay et al has also reported similar results [ 12 ].…”

Section: Discussionmentioning

confidence: 72%

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The Effect of Empagliflozin on Liver Fat in Type 2 Diabetes Mellitus Patients With Non-Alcoholic Fatty Liver Disease

Pokharel¹,

Kc²,

Thapa³

et al. 2021

Cureus

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Background and objectiveThe prevalence of non-alcoholic fatty liver disease (NAFLD) is 60% in patients with type 2 diabetes mellitus (T2DM). NAFLD can lead to non-alcoholic steatohepatitis (NASH), both of which are the leading causes of cirrhosis. This study was undertaken to evaluate whether empagliflozin, a sodium-glucose cotransporter-2 (SGLT-2) inhibitor, reduces liver fat content in these patients after therapy. MethodsAfter enrolling patients of T2DM with NAFLD, they were administered empagliflozin 10 mg once daily orally for six months without modifying existing oral hypoglycemic agents (OHA) if any. All demographic data were collected, and anthropometric measurements, as well as laboratory investigations, were performed, and controlled attenuation parameter (CAP) and liver stiffness (LS) were measured using FibroScan® (Echosens, Paris, France) at baseline, and six months of therapy. The adverse effects related to therapy were also taken into account. ResultsThere was a significant decrease in mean CAP value from 282.07 ± 47.29 dB/m to 263.07 ± 49.93 dB/m and LS from 5.89 ± 4.23 kPa to 5.04 ± 1.49 kPa along with a significant decrease in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) among the patients. Compared to the baseline, there was a significant reduction in post-treatment weight, body mass index (BMI), and blood pressure (BP). The most commonly observed adverse effects of the therapy were urinary tract infection (UTI) (17.8%), nasopharyngitis (11.9%), and hypoglycemia (10.71%). ConclusionA reduction in hepatic fat content was seen in our prospective study cohort after six months of empagliflozin therapy. Empagliflozin also led to beneficial effects such as weight loss and reduction in transaminases and GGT. Given the absence of significant side effects of the therapy, empagliflozin could be used as an effective treatment modality for T2DM patients with NAFLD, which are two conditions commonly seen in combination.

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Section: Discussionmentioning

confidence: 72%

“…A similar finding was noted in a study by Shimizu et al where there was a significant decrease in CAP from 314 ± 61 to 290 ± 73 dB/m (p=0.0424) [ 15 ]. Studies by Chehrehgosha et al and Taheri et al have also shown a reduction in CAP values [ 16 , 17 ].…”

Section: Discussionmentioning

confidence: 97%

The Effect of Empagliflozin on Liver Fat in Type 2 Diabetes Mellitus Patients With Non-Alcoholic Fatty Liver Disease

Pokharel¹,

Kc²,

Thapa³

et al. 2021

Cureus

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“…Specifically, SGLT2i reduced liver fat, assessed by MRI or a controlled attenuation parameter (CAP), liver transaminases and markers of liver fibrosis (assessed by fibrosis scores or transient elastography) in patients with NAFLD and T2DM [3,5]. Among the SGLT2i, empagliflozin has been evaluated in several randomized controlled trials [8][9][10] and has been shown to reduce liver fat and liver stiffness measurements [8][9][10]. Interestingly, empagliflozin exerted these beneficial effects on the liver status in patients with T2DM even when they had excellent glycemic control and a short known disease duration [9], suggesting that its effects may be, at least partially, independent of glycemic status.…”

Section: Introductionmentioning

confidence: 99%

Empagliflozin Improves Metabolic and Hepatic Outcomes in a Non-Diabetic Obese Biopsy-Proven Mouse Model of Advanced NASH

Perakakis

Chrysafi

Feigh

et al. 2021

IJMS

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Empagliflozin, an established treatment for type 2 diabetes (T2DM), has shown beneficial effects on liver steatosis and fibrosis in animals and in humans with T2DM, non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH). However, little is known about the effects of empagliflozin on liver function in advanced NASH with liver fibrosis and without diabetes. This study aimed to assess the effects of empagliflozin on hepatic and metabolic outcomes in a diet-induced obese (DIO) and insulin-resistant but non-diabetic biopsy-confirmed mouse model of advanced NASH. Male C57BL/6JRj mice with a biopsy-confirmed steatosis and fibrosis on AMLN diet (high fat, fructose and cholesterol) for 36-weeks were randomized to receive for 12 weeks: (a) Empagliflozin (10 mg/kg/d p.o.), or (b) vehicle. Metabolic outcomes, liver pathology, markers of Kupffer and stellate cell activation and lipidomics were assessed at the treatment completion. Empagliflozin did not affect the body weight, body composition or insulin sensitivity (assessed by intraperitoneal insulin tolerance test), but significantly improved glucose homeostasis as assessed by oral glucose tolerance test in DIO-NASH mice. Empagliflozin improved modestly the NAFLD activity score compared with the vehicle, mainly by improving inflammation and without affecting steatosis, the fibrosis stage and markers of Kupffer and stellate cell activation. Empagliflozin reduced the hepatic concentrations of pro-inflammatory lactosylceramides and increased the concentrations of anti-inflammatory polyunsaturated triglycerides. Empagliflozin exerts beneficial metabolic and hepatic (mainly anti-inflammatory) effects in non-diabetic DIO-NASH mice and thus may be effective against NASH even in non-diabetic conditions.

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“…After removing duplicates and screening the titles and abstracts for irrelevant studies based on the topic or research type, 27 studies were selected for the full-text review. In the end, 20 studies [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] were included in our meta-analysis, including 15 RCTs [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] (two were three-arm RCTs [15 , 20] and one was a four-arm RCT [23] ). Supplementary Figure 1 shows the flow chart of the review.…”

Section: Baseline Characteristicsmentioning

confidence: 99%

The safety and efficacy evaluation of sodium-glucose co-transporter 2 inhibitors for patients with non-alcoholic fatty liver disease: An updated meta-analysis

Huang

Liang

et al. 2022

Digestive and Liver Disease

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Background: In recent years, sodium-glucose co-transporter 2 inhibitors (SGLT2is) have been increasingly used in the treatment of patients with non-alcoholic fatty liver disease (NAFLD). This updated metaanalysis aimed to evaluate the efficacy and safety of SGLT2is for patients with NAFLD. Methods: PubMed, Embase, Cochrane Library, Web of Science, Wan Fang, China National Knowledge Infrastructure and VIP databases were searched for relevant studies from inception to April 30, 2021. Values of weighted mean differences (WMDs) and risk ratios (RRs) were determined for continuous and dichotomous outcomes, respectively. Results: A total of 1,498 patients with NAFLD from 20 studies were included for further analysis. Pooled analyses indicated significant improvements in body mass index [WMD: −0.84 kg/m 2 , 95% CI ( −1.09, −0.60)], alanine aminotransferase [WMD: −4.36 U/L, 95% CI ( −7.17, −1.54)], aspartate aminotransferase [WMD: −2.94 U/L, 95% CI ( −5.33, −0.55)], fasting plasma glucose [WMD: −4.08 mmol/L, 95% CI ( −6.21, −1.95)] and fibrosis-4 index [WMD: −0.08, 95% CI ( −0.11, −0.05)] following SGLT2i treatment ( p < 0.01 for all above parameters). There was no significant difference in the incidence of total adverse events between the SGLT2i group and the control group (RR = 0.78, 95% CI (0.58, 1.06), p = 0.11]. Conclusion: SGLT2is seem to be a promising treatment for patients with NAFLD to improve metabolic and fibrosis indexes without increasing the incidence of adverse events. Most included studies were conducted in NAFLD patients with diabetes. Therefore, the results of this meta-analysis are more applicable to the diabetic population.

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Empagliflozin Improves Liver Steatosis and Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease and Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Cited by 101 publications

References 80 publications

The Effect of Empagliflozin on Liver Fat in Type 2 Diabetes Mellitus Patients With Non-Alcoholic Fatty Liver Disease

The Effect of Empagliflozin on Liver Fat in Type 2 Diabetes Mellitus Patients With Non-Alcoholic Fatty Liver Disease

Empagliflozin Improves Metabolic and Hepatic Outcomes in a Non-Diabetic Obese Biopsy-Proven Mouse Model of Advanced NASH

The safety and efficacy evaluation of sodium-glucose co-transporter 2 inhibitors for patients with non-alcoholic fatty liver disease: An updated meta-analysis

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