Comparison of sodium-glucose cotransporter-2 inhibitors and thiazolidinediones for management of non-alcoholic fatty liver disease: A systematic review and meta-analysis

Hameed, Ishaque; Hayat, Javeria; Marsia, Shayan; Samad, Syed Abdus; Khan, Rafay; Siddiqui, Omer Mustafa; Khan, Mohammad Omer; Malik, Shanza; Fatima, Kaneez; Fudim, Marat; Krasuski, Richard A.

doi:10.1016/j.clinre.2023.102111

Cited by 11 publications

(2 citation statements)

References 33 publications

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“…Intriguingly, a meta-analysis focusing on comparison of SGLT2 inhibitors and TZDs for management of NAFLD showed that the improvement in liver enzymes and hepatic steatosis and fibrosis were similar between SGLT2 inhibitors and TZDs. 31 We also found that pioglitazone treatment decreased NAFLD liver fat score significantly compared to placebo in the present study. However, we did not find a significant improvement in other surrogate indices for hepatic steatosis such as FLI or HSI by pioglitazone add-on therapy.…”

Section: Discussionsupporting

confidence: 79%

A multicentre, double‐blind, placebo‐controlled, randomized, parallel comparison, phase 3 trial to evaluate the efficacy and safety of pioglitazone add‐on therapy in type 2 diabetic patients treated with metformin and dapagliflozin

Lim,

Lee,

Min

et al. 2024

Diabetes Obesity Metabolism

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AimTo investigate the efficacy and safety of pioglitazone compared to placebo when added to metformin plus dapagliflozin, a sodium‐glucose cotransporter‐2 (SGLT2) inhibitor, for patients with type 2 diabetes mellitus (T2DM).Materials and MethodsIn a multicentre study, with a randomized, double‐blind, placebo‐controlled design, 249 Korean patients with T2DM suboptimally managed on metformin and dapagliflozin were assigned to receive either pioglitazone (15 mg daily) or placebo for 24 weeks, followed by a 24‐week pioglitazone extension. Primary outcomes included changes in glycated haemoglobin (HbA1c), with secondary outcomes assessing insulin resistance, adiponectin levels, lipid profiles, liver enzymes, body weight and waist circumference.ResultsPioglitazone administration resulted in a significant reduction in HbA1c levels (from 7.80% ± 0.72% to 7.27% ± 0.82%) compared with placebo (from 7.79% ± 0.76% to 7.69% ± 0.86%, corrected mean difference: −0.42% ± 0.08%; p < 0.01) at 24 weeks. Additional benefits from pioglitazone treatment included enhanced insulin sensitivity, increased adiponectin levels, raised high‐density lipoprotein cholesterol levels and reduced liver enzyme levels, resulting in improvement in nonalcoholic fatty liver disease liver fat score. Despite no serious adverse events in either group, pioglitazone therapy was modestly but significantly associated with weight gain and increased waist circumference.ConclusionsAdjunctive pioglitazone treatment in T2DM inadequately controlled with metformin and dapagliflozin demonstrates considerable glycaemic improvement, metabolic benefits, and a low risk of hypoglycaemia. These advantages must be weighed against the potential for weight gain and increased waist circumference.

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Section: Discussionsupporting

confidence: 79%

A multicentre, double‐blind, placebo‐controlled, randomized, parallel comparison, phase 3 trial to evaluate the efficacy and safety of pioglitazone add‐on therapy in type 2 diabetic patients treated with metformin and dapagliflozin

Lim,

Lee,

Min

et al. 2024

Diabetes Obesity Metabolism

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“…A clinical study involving 156 patients showed that treatment with SGLT-2 inhibitors not only improved blood glucose control in patients with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D), but also significantly F. Yang, X. P. Tan [20] Ipragliflozin HbA1c, BMI HbA1c↓, BMI↓ [21] reduced patients' visceral fat area (VFA) and body weight. [13]. SGLT-2 inhibitors can reduce liver fat content, and reduce fat mass mainly by reducing visceral fat to achieve body weight loss.…”

Section: Effects Of Sglt-2 Inhibitors On Hepatic Fat Accumulationmentioning

confidence: 99%

Progress in the Study of the Hepatoprotective Effect of SGLT2i on NAFLD Patients with T2DM

Yang,

Tan

2024

JBM

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In recent years, the progress of NAFLD has become an important health problem, and the prevention or delay of progress in NAFLD is a major key point. Whether or not to combine T2MD, people are interested in the mechanisms and efficacy of SGLT2i for NAFLD. In this review, we summarized the current clinical research on SGLT2i for the combination of T2MD's NAFLD patients, and the latest evidence of external or animal experiments. These evidences will help us to more accurately understand the protective effects of SGLT2i in NAFLD. Lifestyle changes are still essential to prevent and treat NAFLD, and for all kinds of drugs that treat NAFLD in clinical trials, SGLT2i may be one of the promising treatments.

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Genetically Proxied Antidiabetic Drug Target and Primary Open‐Angle Glaucoma: A Mendelian Randomization Study

Tang,

Wang,

Chang

et al. 2024

Health Science Reports

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Background and AimsObservational studies suggest that antidiabetic drugs may lower POAG risk; while the causal relationship remains unclear. Naturally occurring variation in genes encoding antidiabetics drug targets can be used as proxies to investigate long‐term therapeutic effect of these drugs on POAG risk.MethodsWe performed a two‐sample Mendelian randomization study to evaluate the potential effect of antidiabetic drug targets on POAG in Europeans and East Asians. To proxy antidiabetic drugs (ABCC8, PPARG, GLP1R, SLC5A2), we leveraged genetic variants located near or within drug target genes that were associated with HbA1c. The validity of our ancestry‐specific genetic instrument was checked with multipul positive control outcomes. Genetic summary statistics of POAG from the International Glaucoma Genetics Consortium, Global Biobank Meta‐analysis Initiative, and FinnGen consortia were analyzed for Europeans (38,164 cases and 1,576,179 controls) and East Asians (16,650 cases and 288,833 controls) separately. Inverse‐variance weighted random‐effects models were used as primary method.ResultsMR results provided consistent evidence of a protective effect of ABCC8 inhibition on POAG using data sets from IGG, GBMI, and FinnGen. Genetically predicted one‐standard deviation reduction in HbA1c from ABCC8 inhibition were significant associated with lower risk of POAG in Europeans (OR = 0.211, 95% CI: 0.133–0.333; p < 0.001) and East Asians (OR = 0.070, 95% CI: 0.011–0.459; p = 0.0056). The association between genetically predicted ABCC8 inhibition and risk of POAG was mainly mediated through intraocular pressure. No association was found for PPARG, SLC5A2, or GLP1R. Sensitivity analyses supported this observation.ConclusionsWe found a protective effect of genetically proxied ABCC8 inhibition on POAG risk in both Europeans and East Asians, highlighting ABCC8 as a promising candidate drug target for POAG, and mechanisms underlying the protective effect should also be investigated.

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Comparison of sodium-glucose cotransporter-2 inhibitors and thiazolidinediones for management of non-alcoholic fatty liver disease: A systematic review and meta-analysis

Cited by 11 publications

References 33 publications

A multicentre, double‐blind, placebo‐controlled, randomized, parallel comparison, phase 3 trial to evaluate the efficacy and safety of pioglitazone add‐on therapy in type 2 diabetic patients treated with metformin and dapagliflozin

A multicentre, double‐blind, placebo‐controlled, randomized, parallel comparison, phase 3 trial to evaluate the efficacy and safety of pioglitazone add‐on therapy in type 2 diabetic patients treated with metformin and dapagliflozin

Progress in the Study of the Hepatoprotective Effect of SGLT2i on NAFLD Patients with T2DM

Genetically Proxied Antidiabetic Drug Target and Primary Open‐Angle Glaucoma: A Mendelian Randomization Study

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