Effect of dapagliflozin on liver and pancreatic fat in patients with type 2 diabetes and non-alcoholic fatty liver disease

Shi, Mengran; Zhang, Hao; Wang, Wei; Zhang, Xiao; Liu, Jiawei; Wang, Qixian; Wang, Yuan; Zhang, Chunlin; Guo, Xiaoqin; Qiao, Qiao; Cui, Chun; Xu, Jing; Wang, Jian

doi:10.1016/j.jdiacomp.2023.108610

Cited by 6 publications

(5 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This link between oxidative stress and inflammation underscores the intricate interplay between oxidative damage and the immune response, contributing to the pathogenesis of various diseases [33]. Dapagliflozin exhibited a significant reduction in IL-1 beta, IL-6, and TNF-alpha, aligning with studies emphasizing its anti-inflammatory effects [34][35][36]. The combination of dapagliflozin and silymarin displayed a robust suppression of inflammatory biomarkers, indicating a potential synergistic effect.…”

Section: Discussionsupporting

confidence: 52%

Unlocking Synergistic Hepatoprotection: Dapagliflozin and Silymarin Combination Therapy Modulates Nuclear Erythroid 2-Related Factor 2/Heme Oxygenase-1 Pathway in Carbon Tetrachloride-Induced Hepatotoxicity in Wistar Rats

Satyam,

Bairy,

Rehman

et al. 2024

Biology

View full text Add to dashboard Cite

This study was aimed to investigate the hepatoprotective potential of dapagliflozin and silymarin alone and in combination to combat carbon tetrachloride (CCl4)-induced hepatotoxicity and the anticipated mechanisms. Thirty female Wistar rats were randomly allocated into five different groups. All the experimental animals except the normal control (Group I) were administered CCl4. Additionally, Groups II, III, IV, and V were treated with gum acacia, silymarin, dapagliflozin, and a combination of dapagliflozin and silymarin, respectively, for 14 days. Dapagliflozin, silymarin alone, and in combination, significantly reduced (p < 0.05) serum levels of ALT, AST, AST:ALT ratio, and total bilirubin compared to CCl4-intoxicated control rats. There was a notable reduction (p < 0.05) observed in the levels of IL-1beta, IL-6, TNF-alpha, nitrites, and 4-hydroxynonenal, accompanied by an elevation in catalase, superoxide dismutase, glutathione peroxidase, nuclear erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) in liver homogenates of the groups treated with dapagliflozin, silymarin alone, and in combination, as compared to the CCl4-intoxicated control group. Dapagliflozin in combination with silymarin showed a synergistic hepatoprotective effect. Our study reveals the profound hepatoprotective potential of dapagliflozin alone and in combination with silymarin in CCl4-intoxicated Wistar rats by modulating the Nrf2 and HO-1 signaling pathways.

show abstract

Section: Discussionsupporting

confidence: 52%

Unlocking Synergistic Hepatoprotection: Dapagliflozin and Silymarin Combination Therapy Modulates Nuclear Erythroid 2-Related Factor 2/Heme Oxygenase-1 Pathway in Carbon Tetrachloride-Induced Hepatotoxicity in Wistar Rats

Satyam,

Bairy,

Rehman

et al. 2024

Biology

View full text Add to dashboard Cite

show abstract

“…Five (four prospective and one retrospective) clinical studies investigated changes in IPFD following the administration of SGLT-2 inhibitors in individuals with T2DM or prediabetes [ 42 – 46 ]. In addition to SGLT-2 inhibitors, individuals with T2DM received other glucose-lowering medications (including insulin in two studies [ 42 , 43 ]).…”

Section: Glucose-lowering Medicationsmentioning

confidence: 99%

“…The retrospective study identified 22 individuals in Japan over a 6-year study period and found no significant difference in IPFD (determined with the use of computed tomography) before and after administration of SGLT-2 inhibitors [ 42 ]. All the four prospective studies used a magnetic resonance system at 3T to determine IPFD and the sample size of these studies ranged from 30 to 78 individuals [ 43 – 46 ]. Three out of four prospective studies were randomised controlled trials, including two placebo-controlled trials [ 43 , 44 ].…”

Section: Glucose-lowering Medicationsmentioning

confidence: 99%

“…Three out of four prospective studies were randomised controlled trials, including two placebo-controlled trials [ 43 , 44 ]. A study from India found an absolute reduction in IPFD by 1.5% (a relative reduction of 20%) following 17 weeks of dapagliflozin use [ 45 ], and a study from China showed an absolute reduction in IPFD by 1.2% (a relative reduction of 20%) following 24 weeks of dapagliflozin use [ 46 ]. The IPFD change was independent of weight change in the Chinese study [ 46 ] and dependent of weight change in the Indian study [ 45 ].…”

Section: Glucose-lowering Medicationsmentioning

confidence: 99%

“…A study from India found an absolute reduction in IPFD by 1.5% (a relative reduction of 20%) following 17 weeks of dapagliflozin use [ 45 ], and a study from China showed an absolute reduction in IPFD by 1.2% (a relative reduction of 20%) following 24 weeks of dapagliflozin use [ 46 ]. The IPFD change was independent of weight change in the Chinese study [ 46 ] and dependent of weight change in the Indian study [ 45 ]. The two placebo-controlled trials used empagliflozin as the study intervention and they came from Germany and France [ 43 , 44 ].…”

Section: Glucose-lowering Medicationsmentioning

confidence: 99%

See 2 more Smart Citations

The Pharmacological Landscape for Fatty Change of the Pancreas

Petrov

2024

Drugs

View full text Add to dashboard Cite

The quest for medications to reduce intra-pancreatic fat deposition is now quarter a century old. While no specific medication has been approved for the treatment of fatty change of the pancreas, drug repurposing shows promise in reducing the burden of the most common disorder of the pancreas. This leading article outlines the 12 classes of medications that have been investigated to date with a view to reducing intra-pancreatic fat deposition. Information is presented hierarchically—from preclinical studies to retrospective findings in humans to prospective interventional studies to randomised controlled trials. This lays the grounds for shepherding the most propitious drugs into medical practice through well-designed basic science studies and adequately powered randomised controlled trials.

show abstract

SGLT2 inhibitors and AMPK: The road to cellular housekeeping?

Safaie,

Masoumi,

Alizadeh

et al. 2024

Cell Biochemistry & Function

View full text Add to dashboard Cite

Sodium‐glucose co‐transporter‐2 (SGLT2) inhibitors, known as Gliflozins, are a class of Glucose‐lowering drugs in adults with type 2 diabetes (T2D) that induce glucosuria by blocking SGLT2 co‐transporters in the proximal tubules. Several lines of evidence suggest that SGLT2 inhibitors regulate multiple mechanisms associated with the regulation of varying cellular pathways. The 5′‐adenosine monophosphate‐activated protein kinase (AMPK) pathway plays an important role in metabolic homeostasis by influencing cellular processes. Recently, it has been shown that SGLT2 inhibitors can affect the AMPK pathway in differing physiological and pathological ways, resulting in kidney, intestinal, cardiovascular, and liver protective effects. Additionally, they have therapeutic effects on nonalcoholic fatty liver disease and diabetes mellitus‐associated complications. In this review, we summarize the results of studies of AMPK‐associated therapeutic effects of SGLT2 inhibitors in different organelle functions.

show abstract

Effect of dapagliflozin on liver and pancreatic fat in patients with type 2 diabetes and non-alcoholic fatty liver disease

Cited by 6 publications

References 41 publications

Unlocking Synergistic Hepatoprotection: Dapagliflozin and Silymarin Combination Therapy Modulates Nuclear Erythroid 2-Related Factor 2/Heme Oxygenase-1 Pathway in Carbon Tetrachloride-Induced Hepatotoxicity in Wistar Rats

Unlocking Synergistic Hepatoprotection: Dapagliflozin and Silymarin Combination Therapy Modulates Nuclear Erythroid 2-Related Factor 2/Heme Oxygenase-1 Pathway in Carbon Tetrachloride-Induced Hepatotoxicity in Wistar Rats

The Pharmacological Landscape for Fatty Change of the Pancreas

SGLT2 inhibitors and AMPK: The road to cellular housekeeping?

Contact Info

Product

Resources

About