Effects of Sodium/Glucose Cotransporter 2 (SGLT2) Inhibitors and Combined SGLT1/2 Inhibitors on Cardiovascular, Metabolic, Renal, and Safety Outcomes in Patients with Diabetes: A Network Meta-Analysis of 111 Randomized Controlled Trials

Teo, Yao Neng; Ting, Adriel Z. H.; Teo, Yao Hao; Chong, Elliot Yeung; Tan, Joshua; Syn, Nicholas; Chia, Alfred; Ong, How Ting; Cheong, Alex Jia Yang; Li, Tony Yi‐Wei; Poh, Kian Keong; Yeo, Tiong Cheng; Chan, Mark Y; Wong, Raymond Cc; Chai, Ping; Sia, Ching‐Hui

doi:10.1007/s40256-022-00528-7

Cited by 20 publications

(16 citation statements)

References 39 publications

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“…In this scenario, SGLT2 (sodium glucose cotransporter 2) inhibitors, which include the Food and Drug Administration–approved drugs canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin, 12 are considered among the most promising oral antidiabetic drugs to reach and maintain an optimal glycemic control in older subjects. 13 The main mechanism of action of these drugs is the blockage of SGLT2 proteins in the renal proximal convoluted tubules to reduce the reabsorption of filtered glucose and decrease the renal threshold for glucose, thereby promoting urinary glucose excretion.…”

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confidence: 99%

SGLT2 Inhibition via Empagliflozin Improves Endothelial Function and Reduces Mitochondrial Oxidative Stress: Insights From Frail Hypertensive and Diabetic Patients

et al. 2022

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Background: Frailty is a multidimensional condition often diagnosed in older adults with hypertension and diabetes, and both these conditions are associated with endothelial dysfunction and oxidative stress. We investigated the functional role of the SGLT2 (sodium glucose cotransporter 2) inhibitor empagliflozin in frail diabetic and hypertensive older adults. Methods: We studied the effects of empagliflozin in consecutive hypertensive and diabetic older patients with frailty presenting at the ASL (local health unit of the Italian Ministry of Health) of Avellino, Italy, from March 2021 to January 2022. Moreover, we performed in vitro experiments in human endothelial cells to measure cell viability, permeability, mitochondrial Ca 2+ , and oxidative stress. Results: We evaluated 407 patients; 325 frail elders with diabetes successfully completed the study. We propensity-score matched 75 patients treated with empagliflozin and 75 with no empagliflozin. We observed a correlation between glycemia and Montreal Cognitive Assessment (MoCA) score and between glycemia and 5-meter gait speed (5mGS). At 3-month follow-up, we detected a significant improvement in the MoCA score and in the 5mGS in patients receiving empagliflozin compared with non-treated subjects. Mechanistically, we demonstrate that empagliflozin significantly reduces mitochondrial Ca 2+ overload and reactive oxygen species production triggered by high glucose in human endothelial cells, attenuates cellular permeability, and improves cell viability in response to oxidative stress. Conclusions: Taken together, our data indicate that empagliflozin reduces frailty in diabetic and hypertensive patients, most likely by decreasing the mitochondrial generation of reactive oxygen species in endothelial cells.

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confidence: 99%

SGLT2 Inhibition via Empagliflozin Improves Endothelial Function and Reduces Mitochondrial Oxidative Stress: Insights From Frail Hypertensive and Diabetic Patients

et al. 2022

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“…The other SGLT-2 inhibitors, such as ipragliflozin, 114,124 luseogliflozin, 125,126 and tofogliflozin, 114 also showed the benefits on reduction of metabolic syndrome for DM patients, supporting the potential role in treatment for MAFLD.…”

Section: Strategy For Targeting Dm and Mafld Simultaneously: Adamentioning

confidence: 81%

“…One study also claimed that dapagliflozin is the most effective SGLT-2 inhibitor for reducing GGT level compared with other SGLT-2 inhibitors. 114 The other SGLT-2 inhibitors, such as ipragliflozin, 114,124 luseogliflozin, 125,126 and tofogliflozin, 114 also showed the benefits on reduction of metabolic syndrome for DM patients, supporting the potential role in treatment for MAFLD.…”

Section: Strategy For Targeting Dm and Mafld Simultaneously: Adamentioning

confidence: 91%

To Do One and To Get More: Part II. Diabetes and metabolic dysfunction-associated fatty liver diseases

Lee

Wang

Yang

et al. 2022

Journal of the Chinese Medical Association

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Type 2 diabetes mellitus (DM) is characterized by inability of faulty pancreatic β-cells to secret a normal amount of insulin to maintain normal body consumption, and/or peripheral tissue has a decreased susceptibility to insulin, resulting in hyperglycemia and insulin resistance. Similar to other chronic systemic inflammatory diseases, DM is a result from dysregulated interactions between ethnic, genetic, epigenetic, immunoregulatory, hormonal, and environmental factors. Therefore, it is rational to suppose the concept as “To do one and to get more”, while using antidiabetic agents (ADA), a main pharmacologic agent for the treatment of DM, can provide an extraglycemia effect on comorbidities or concomittent comorbidities to DM. In this review, based on the much strong correlation between DM and metabolic dysfunction-associated fatty liver diseases (MAFLD) shown by similar pathophysiological mechanisms and a high prevalence of DM in MAFLD and its vice versa (a high prevalence of MAFLD in DM), it is possible to use the strategy to target both diseases simultaneously. We focus on a new classification of ADA, such as glucagon-like peptide-1 receptor (GLP1R) agonist and sodium-glucose cotransporter-2 (SGLT-2) inhibitors to show the potential benefits of extraglycemic effect on MAFLD. We conclude that the management of DM patients, especially for those who need ADA as adjuvant therapy should include healthy lifestyle modification to overcome the metabolic syndrome, contributing to the urgent need of an effective weight-reduction strategy. GLP1R agonist is one of effective body weight-lowering medications, which may be a better choice for DM complicated with MAFLD or its-associated severe form as metabolic associated steatohepatitis (MASH), although the role of SGLT-2 inhibitors is also impressive. The prescription of these two classes of ADA may satisfy the concept “To do one and to get more”, based on successful sugar-lowering effect for controlling DM and extraglycemia benefits of hepatoprotective activity in DM patients.

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“…The recent development of combined sodium-glucose cotransporter 1/2 (SGLT1/SGLT2) inhibitors such as Sotagliflozin (LX-4211) and Licogliflozin (LIK066) have shown similar promise in reducing BP [17][18][19]. By additionally inhibiting sodium-glucose cotransporter 1 (SGLT1) transporter, it also inhibits intestinal glucose absorption, hence blunting and delaying postprandial hyperglycaemia and achieving additional metabolic benefits [18,20].…”

Section: Introductionmentioning

confidence: 99%

The impact of sodium–glucose cotransporter inhibitors on blood pressure: a meta-analysis and metaregression of 111 randomized-controlled trials

Teo

Chia

Teo

et al. 2022

Journal of Hypertension

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Objective: Multiple trials on sodium-glucose cotransporter (SGLT) inhibitors have been performed recently demonstrating blood pressure (BP) reduction benefits in both diabetic and nondiabetic patients. Hence, we conducted a systematic review and meta-analysis to determine the effect of different SGLT inhibitors on BP in both patients with and without diabetes mellitus.Methods: Four electronic databases (PubMed, Embase, Cochrane, and SCOPUS) were searched on 4 November 2021 for articles published from 1 January 2000 up to 21 November 2021, for studies evaluating the BP effects of SGLT inhibitors. Pair-wise meta-analysis and random effects metaregression models were utilized.Results: In total, 111 studies examining SBP (108 studies, 104 304 patients) and/or DBP (82 studies, 74 719 patients) were included. In patients with diabetes, the random effects model demonstrated SGLT inhibitor produced a mean reduction in SBPs of À3.46 mmHg (95% confidence interval: À3.83, À3.09) compared with placebo. There were no statistically significant changes in BP among patients without diabetes. Drug response relationship was not observed in SGLT inhibitors and BP, except for Canagliflozin and DBP.Conclusion: Sodium-glucose cotransporter 2 inhibitors and combined sodium-glucose cotransporter 1/2 inhibitors produced small reductions in BP in patients with diabetes.

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Effects of Sodium/Glucose Cotransporter 2 (SGLT2) Inhibitors and Combined SGLT1/2 Inhibitors on Cardiovascular, Metabolic, Renal, and Safety Outcomes in Patients with Diabetes: A Network Meta-Analysis of 111 Randomized Controlled Trials

Cited by 20 publications

References 39 publications

SGLT2 Inhibition via Empagliflozin Improves Endothelial Function and Reduces Mitochondrial Oxidative Stress: Insights From Frail Hypertensive and Diabetic Patients

SGLT2 Inhibition via Empagliflozin Improves Endothelial Function and Reduces Mitochondrial Oxidative Stress: Insights From Frail Hypertensive and Diabetic Patients

To Do One and To Get More: Part II. Diabetes and metabolic dysfunction-associated fatty liver diseases

The impact of sodium–glucose cotransporter inhibitors on blood pressure: a meta-analysis and metaregression of 111 randomized-controlled trials

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