Efficacy and Safety of Ranolazine in Diabetic Patients: A Systematic Review and Meta-analysis

Zeng, Xiaofang; Zhang, Yinyin; Lin, Jie; Zheng, Hongyu; Peng, Jie; Huang, Wei

doi:10.1177/1060028017747901

Cited by 9 publications

(8 citation statements)

References 38 publications

(125 reference statements)

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“…Ranolazine improves ATP production and O2 consumption by stimulating glucose oxidation and decreasing fatty acid oxidation [ 85 ]. In type 2 diabetic patients, RN has been shown to offer a variety of effects, including lowering blood glucose and glycosylated haemoglobin levels, promoting insulin release, and decreasing glucagon synthesis, therefore improving pre- and postprandial blood glucose [ 86 , 87 , 88 , 89 ]. Rn reduced the pro-inflammatory profile and improved learning and long-term memory in a Wistar rat model of type 2 diabetes.…”

Section: Discussionmentioning

confidence: 99%

Facilitation of Insulin Effects by Ranolazine in Astrocytes in Primary Culture

Vallés

Aldasoro

Campo-Palacio

et al. 2022

IJMS

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Ranolazine (Rn) is a drug used to treat persistent chronic coronary ischemia. It has also been shown to have therapeutic benefits on the central nervous system and an anti-diabetic effect by lowering blood glucose levels; however, no effects of Rn on cellular sensitivity to insulin (Ins) have been demonstrated yet. The present study aimed to investigate the permissive effects of Rn on the actions of Ins in astrocytes in primary culture. Ins (10−8 M), Rn (10−6 M), and Ins + Rn (10−8 M and 10−6 M, respectively) were added to astrocytes for 24 h. In comparison to control cells, Rn and/or Ins caused modifications in cell viability and proliferation. Rn increased protein expression of Cu/Zn-SOD and the pro-inflammatory protein COX-2 was upregulated by Ins. On the contrary, no significant changes were found in the protein expression of NF-κB and IκB. The presence of Rn produced an increase in p-ERK protein and a significant decrease in COX-2 protein expression. Furthermore, Rn significantly increased the effects of Ins on the expression of p-AKT, p-eNOS, p-ERK, Mn-SOD, and PPAR-γ. In addition, Rn + Ins produced a significant decrease in COX-2 expression. In conclusion, Rn facilitated the effects of insulin on the p-AKT, p-eNOS, p-ERK, Mn-SOD, and PPAR-γ signaling pathways, as well as on the anti-inflammatory and antioxidant effects of the hormone.

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Section: Discussionmentioning

confidence: 99%

Facilitation of Insulin Effects by Ranolazine in Astrocytes in Primary Culture

Vallés

Aldasoro

Campo-Palacio

et al. 2022

IJMS

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show abstract

“…Ranolazine improves ATP production and O2 consumption by stimulating glucose oxidation and decreasing fatty acid oxidation [85]. In type 2 diabetic patients, RN has been shown to offer a variety of effects, including lowering blood glucose and glycosylated haemoglobin levels, promoting insulin release, and decreasing glucagon synthesis, therefore improving pre-and postprandial blood glucose [86][87][88][89]. Rn reduced the proinflammatory profile and improved learning and long-term memory in a Wistar rat model of type 2 diabetes.…”

Section: Discussionmentioning

confidence: 99%

Facilitation of Insulin Effects by Ranolazine in Astrocytes in Primary Culture

Vallés¹,

Aldasoro²,

Palacio³

et al. 2022

Preprint

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Ranolazine (Rn) is a drug used to treat persistent chronic coronary ischemia. It has also been shown to have therapeutic benefits on the central nervous system and an anti-diabetic effect by lowering blood glucose levels and however, no effects of Rn on cellular sensitivity to insulin (Ins) have been demonstrated yet. The present study aimed to investigate the permissive effects of Rn on the actions of Ins in astrocytes in primary culture. Ins at 10-8 M, Rn (10-6 M) and Ins+Rn (10-8 M and 10−6 M respectively) were added to astrocytes during 24 h. In comparison to control cells, Rn and/or Ins caused modifications in cell viability and proliferation. p-AKT, p-ERK, p-eNOS, Mn-SOD, COX-2, and the anti-inflammatory protein COX-2 were all upregulated by ins. On the contrary, no significant changes were found in the protein expression of Cu/Zn-SOD, NF-κB and IκB. The presence of Rn produced an increase in p-ERK protein and a significant decrease in COX-2 protein expression. Furthermore, Rn significantly increased the effects of Ins on the expression of p-AKT, p-eNOS, p-ERK, Mn-SOD, and PPAR-γ. On the other hand, Rn+Ins produced a significant decrease in COX-2 expression. In conclusion, Rn facilitated the effects of insulin on the p-AKT, p-eNOS, p-ERK, Mn-SOD and PPAR-γ, signaling pathways, as well as on the anti-inflammatory and antioxidant effects of the hormone.

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“…Despite its demonstrated propriety of lowering HbA1c, studies using R as a direct oral glucose-lowering agent in T2DM subjects without CHD are still preliminary and conclusion cannot be drawn as recently underlined by the meta-analysis of Zeng et al [34] . In particular the effect size produced by R in diabetic patients when used in monotherapy or in association with other glucose-lowering drugs remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Glyco-metabolic Effects of Ranolazine: A truly Multifaceted Drug?

Caminiti

Massaro

Fossati

et al. 2018

Journal of Cardiology and Therapy

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other possible clinical applications of R have also been explored, including treatment of atrial arrhythmias, chronic heart failure and diabetes. With regard to diabetes R has been shown to significantly improve glycemic control in diabetic patients with CHD in posthoc analyses of large-scale clinical trials. Moreover reduction of glycated hemoglobin and fasting serum glucose levels have been also observed prospectively in small clinical trials conducted on diabetic subjects without CHD by using R alone or in combination with other oral glucose-lowering drugs. Lastly, R improved insulin resistance in non-diabetic overweight/obese patients with CHD. Hypothetical mechanisms of this metabolic action are: inhibition of secretion of glucagon from pancreatic islets, preservation of beta cells and increase of insulin delivery to tissues. In light of these observations R appear to be a potential multifaceted drug that offers the opportunity to treat glyco-metabolic disorders alone or in association to CHD. However, prospective studies are too small to be conclusive and new trials are needed to clarify which is the exact role of R in the treatment of glyco-metabolic disorders.

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Efficacy and Safety of Ranolazine in Diabetic Patients: A Systematic Review and Meta-analysis

Abstract: Ranolazine exerts a positive effect on glucose control and is a well-tolerated agent for patients with diabetes.

Cited by 9 publications

References 38 publications

Facilitation of Insulin Effects by Ranolazine in Astrocytes in Primary Culture

Facilitation of Insulin Effects by Ranolazine in Astrocytes in Primary Culture

Facilitation of Insulin Effects by Ranolazine in Astrocytes in Primary Culture

Glyco-metabolic Effects of Ranolazine: A truly Multifaceted Drug?

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