Effect of ranolazine on glycaemic control in patients with type 2 diabetes treated with either glimepiride or metformin

Pettus, Jeremy; McNabb, Brian; Eckel, Robert H.; Skyler, Jay S.; Dhalla, Arvinder K.; Guan, Shu-mei; Jochelson, Philip; Belardinelli, Luiz; Henry, RR

doi:10.1111/dom.12629

Cited by 14 publications

(24 citation statements)

References 21 publications

(28 reference statements)

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“…Only five RCTs provided data on incidence of hypoglycaemia when treated with ranolazine or placebo (Eckel et al ,18 Kipnes et al ,19 Pettus et al – glimepiride add-on (GAO) study,20 Pettus et al – metformin add-on (MAO) study20 and Kosiborod et al 9). All these trials included patients with diabetes.…”

Section: Resultsmentioning

confidence: 99%

“…We also performed meta-analysis on hypoglycaemia incidence for all subjects from five trials (Eckel et al ,18 Kipnes et al 19, Pettus et al 20 – GAO study, Pettus et al 20 – MAO study and Kosiborod et al 9) that provided these data. There was no significant difference in hypoglycaemia incidence between ranolazine and placebo group (OR 1.70, 95% CI 0.89 to 3.26, p=0.61; five trials) (figure 3).…”

Section: Resultsmentioning

confidence: 99%

“…Most patients are taking different regimen of antidiabetic medications, except Pettus et al 20 – GAO study and Pettus et al 20 – MAO study. In Pettus et al 20 – GAO study, all patients were on sulphonylurea, whereas in Pettus et al 20 – MAO study, all patients were on metformin but none used any sulphonylurea. One of the trials (Morrow et al ) included patients with type 1 and 2 diabetes who have quite different pathophysiological mechanisms of insulin response.…”

Section: Discussionmentioning

confidence: 99%

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Effect of ranolazine on glycaemia in adults with and without diabetes: a meta-analysis of randomised controlled trials

Teoh

Banerjee

2018

Open Heart

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BackgroundRanolazine is an antianginal drug reported to have hypoglycaemic effects.ObjectivesTo assess the effect of ranolazine versus placebo on glycaemic control for adults with and without diabetes.MethodsA systematic search of seven databases was conducted to identify all randomised controlled trials that compared the effect of ranolazine versus placebo on haemoglobin A1c (HbA1c) and/or fasting plasma glucose (FPG) and/or incidence of hypoglycaemia. We used mean differences in HbA1c and FPG to express intervention effect estimates and analysed the data with random-effects model for meta-analyses using Revman 5.3.ResultsWe identified seven trials including 6543 subjects to assess the effect of ranolazine on HbA1c and/or FPG. A separate trial that included 944 subjects was included to assess the effect of ranolazine on hypoglycaemia. The change in HbA1c for all patients was −0.36% (95% CI −0.57% to −0.15%; p=0.0004, I2=78%). In patients with diabetes, the change in HbA1c was −0.41% (95% CI −0.58% to −0.25%; p<0.00001, I2=65%). There was no significant difference in FPG between ranolazine and placebo groups (−2.58 mmol/L, 95% CI −7.02 to 1.85; p=0.25; I2=49%) or incidence of hypoglycaemia between ranolazine and placebo groups (OR 1.70, 95% CI 0.89 to 3.26; p=0.61, I2=0%).ConclusionsOur meta-analytic findings support the fact that ranolazine improves HbA1c without increasing the risk of hypoglycaemia. It therefore has a potential of having an additional benefit of improving glycaemic control in patients with chronic stable angina and diabetes.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Effect of ranolazine on glycaemia in adults with and without diabetes: a meta-analysis of randomised controlled trials

Teoh

Banerjee

2018

Open Heart

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“…The number of subjects achieving an HbA1c < 7.0% at week 24 was greater in the ranolazine group (25.6% placebo and 41.2% ranolazine; p 0.0004). Pettus et al [24] evaluated the efficacy of R (1gr/daily) as adjunct therapy to either metformine or glimepiride in 2 double-blind studies versus placebo. Again the primary study endpoint was change in HbA1c from baseline.…”

Section: Discussionmentioning

confidence: 99%

“…T2DM and CHD, while separate disease processes, have overlapping metabolic pathophysiology [13] : factors typically involved in diabetes such as hyperglycemia, dyslipidemia and insulin resistance, contribute to atherogenic changes like endothelial and smooth muscle cells dysfunction, impaired platelet function and abnormal coagulation. As a consequence of this common pathophysiological ground, in the last few years some drugs originally developed for treating diabetes showed to improve the outcome of subjects with heart disease [14] . Conversely, some drugs used for treating cardiovascular conditions have shown antidiabetic proprieties [15,16] .…”

Section: Glycometabolic Effect Of Ranolazine In Diabetic Patients Witmentioning

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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Avocatin B Protects Against Lipotoxicity and Improves Insulin Sensitivity in Diet‐Induced Obesity

Ahmed

Tcheng

Roma

et al. 2019

Molecular Nutrition Food Res

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ScopeThe effects of an avocado‐derived fatty acid oxidation (FAO) inhibitor, avocatin B (AvoB), on glucose and lipid metabolism in models of diet‐induced obesity (DIO) and in vitro models of lipotoxicity are evaluated. The safety of its oral consumption in humans is also determined.Methods and resultsMice are given high‐fat diets (HFD) for 8 weeks. Thereafter, AvoB or vehicle is administered orally twice weekly for 5 weeks. AvoB inhibits FAO which led to improved glucose tolerance, glucose utilization, and insulin sensitivity. AvoB's effects on metabolism under lipotoxic conditions are evaluated in vitro in pancreatic β‐islet cells and C2C12 myotubes. AvoB inhibits FAO and increases glucose oxidation, resulting in lowering of mitochondrial reactive oxygen species that improves insulin responsiveness in C2C12 myotubes and insulin secretion in INS‐1 (832/13) cells, respectively. A randomized, double‐blind, placebo‐controlled clinical trial in healthy human participants is conducted to assess the safety of AvoB consumption (50 mg or 200 mg per day for 60 days). AvoB is well‐tolerated and not associated with any dose‐limiting toxicity.ConclusionTherapeutic agents that are safe and effectively inhibit FAO and improve DIO‐associated pathologies are currently not available. AvoB's mechanism of action and favorable safety profile highlight its nutritional and clinical importance.

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Effect of ranolazine on glycaemic control in patients with type 2 diabetes treated with either glimepiride or metformin

Cited by 14 publications

References 21 publications

Effect of ranolazine on glycaemia in adults with and without diabetes: a meta-analysis of randomised controlled trials

Effect of ranolazine on glycaemia in adults with and without diabetes: a meta-analysis of randomised controlled trials

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

Avocatin B Protects Against Lipotoxicity and Improves Insulin Sensitivity in Diet‐Induced Obesity

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