INTRODUCTION: Cardiovascular diseases and diabetes mellitus (DM) are two disease entities that commonly coexist in a single patient. Ranolazine is an active piperazine derivative approved by FDA in 2006 as an anti-anginal medication. It was noted to have HbA1c lowering effects in the trials on angina. The proposed mechanism of action is the inhibition of glucagon secretion by blocking the Na v1.3 isoform of sodium channels in pancreatic alpha cells leading to glucagon- and glucose-lowering effects. HbA1c lowering to a target of 6.5% in type 2 diabetes patients has been shown to reduce risk of microvascular complications. The objective of this study is to determine the efficacy and safety of Ranolazine in HbA1c lowering as an add-on therapy to existing anti-diabetic regimen.

METHODS: A comprehensive literature search in PubMed, The Cochrane Central Register of Controlled Trials, the ClinicalTrials.gov website, Google Scholar databases and EMBASE databases were made using the search terms "Randomized controlled trial", "Ranolazine," "HbA1c," and "glycosylated hemoglobin", as well as various combinations of these, was done to identify randomized control trials. No restriction on language and time were done. The authors extracted data for characteristics, quality assessment and mean change in HbA1c after at least eight weeks of treatment with ranolazine. The program RevMan 5.3 was used to generate the statistical analysis of the data.

RESULTS: Six RCTs were included to make up a total of 1,650 diabetic patients. Five studies had moderate risk of bias assessment while one had low risk of bias assessment and hence was not included in the analysis. The overall analysis showed an HbA1c reduction of 0.35% 0.68 to -0.03, p-value=0.03) however, the population was heterogenous (I2=100%). The heterogeneity was not eliminated by sensitivity analysis.

DISCUSSION: The results showed a statistically significant lowering of HbA1c with ranolazine. However, the population was heterogenous. The sources of heterogeneity could be the (1) differences in the level of glycemic control among subjects as indicated by baseline HbA1c levels, (2) the current anti-diabetic regimen of the study patients, i.e. whether or not they are on insulin therapy, (3) the presence or absence of ischemic heart disease and (5) duration of ranolazine therapy, and (4) the presence or absence of chronic kidney disease. When the analysis excluded the population with combination insulin therapy and ranolazine, the effect becomes non-significant. Thus, the HbA1c lowering effect may have been from the insulin therapy rather than the ranolazine.

CONCLUSION: Ranolazine as anti-diabetic therapy shows statistically significant HbA1c lowering effect. It can be a potential treatment option for patients with both DM and angina pectoris. However, well-designed, prospective trials are still recommended to determine the effect on a less heterogenous population. Likewise, more studies are needed to determine its safety.

Human ; Hemoglobin A, Glycosylated ; Glucagon ; Glucagon-secreting Cells ; Diabetes Mellitus, Type 2 ; Ranolazine ; Insulin ; Language ; Prospective Studies ; Blood Glucose ; Angina Pectoris ; Coronary Artery Disease ; Myocardial Ischemia ; Renal Insufficiency, Chronic ; Pubmed ; Sodium Channels ; Protein Isoforms

BACKGROUND: Entamoeba histolytica is an important etiologic agent of diarrhea. Globally, it is estimated to infect 40 to 50 million people and cause 40,000 to 100,000 deaths per year. Metronidazole is effective but can cause adverse reactions in certain individuals. In search of alternatives, traditional medicinal plants are being studied. Several plants in Family Simaroubaceae have shown anti-amoebic activity. Quassia amara, a member of this family has not been tested.
OBJECTIVE: To determine the effect of Q. amara crude extract on Entamoeba histolytica in vitro.
METHODS: Initial testing of 104 µg/ml ethanolic bark extract was performed. Counts were made after 72 hours. Three trials in triplicates were performed.
Nine (9) dilutions of extract were then tested (18.8 to 5,00 µg/ml). Test tubes were checked for viable amoeba after 24-hour and 72-hour incubation. Minimum inhibitory concentrations (MIC) were determined for the two incubation periods. At least two trials in triplicates for each dilution were performed. metronidazole served as positive control.
RESULTS: At 104 µg/ml incubated for 72 hours, no viable amoeba was obtained and counted. The MIC after 24 hours was 5,000 µg/ml, while the MIC at 72 hours was 37.5 µg/ml.
CONCLUSION: Q. amara crude extract has inhibitory effects on E. histolycain vitro.

Human ; Male ; Female ; Aged 80 And Over ; Aged ; Middle Aged ; Adult ; Young Adult ; Adolescent ; Child ; Child Preschool ; Infant ; Infant Newborn ; Quassia ; Metronidazole ; Entamoeba Histolytica ; Plants, Medicinal ; Amoeba ; Simaroubaceae ; Microbial Sensitivity Tests ; Diarrhea