Glycaemic Effects of Non-statin Lipid-Lowering Therapies

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Term Occurence Count Dictionary
fenofibrate 2 endocrinologydiseasesdrugs
metabolic syndrome 1 endocrinologydiseases
niacin 13 endocrinologydiseasesdrugs
pravastatin 2 endocrinologydiseasesdrugs
rosuvastatin 1 endocrinologydiseasesdrugs
bezafibrate 1 endocrinologydiseasesdrugs
diabetes mellitus 4 endocrinologydiseases
ezetimibe 11 endocrinologydiseasesdrugs

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Select Drug Character Offset Drug Term Instance
bezafibrate 6555 longer recommended due to its lack of clinical outcome benefit.FibratesPrior limited evidence suggesting bezafibrate may lower diabetes risk but no clear evidence of an effect of fenofibrate in the FIELD trialMixed genetic
ezetimibe 976 there is clear evidence of a diabetogenic effect for the now outdated but well-studied niacin. For ezetimibe and fibrates, evidence is scarce but currently broadly unconcerning. For now, the glycemic effects of
ezetimibe 7454 clear evidence of increased development of diabetes compared to placebo (HR 0.64 (0.36–1.14)) or ezetimibe (HR 0.55 (0.22–1.41)) [[]••]. Furthermore, there was no significant change in HbA1c over time.
ezetimibe 9512 modestly so, but with stronger associations with diabetes for genes encoding the molecular targets for ezetimibe . Nevertheless, the results of ongoing cardiovascular end-point trials are needed to determine the true
ezetimibe 10138 cardiovascular disease with uncontrolled LDL cholesterol despite maximally tolerated statin and/or ezetimibe therapy—it is unlikely that a modest diabetogenic effect would alter treatment decisions [[]•].NiacinThe
ezetimibe 12685 [[]], but data regarding its glycemic effects are rather limited. Saito et al. randomised diabetics to ezetimibe or placebo and did not find any significant effect on glycemic control (assessed by either HbA1c or
ezetimibe 12931 exacerbations of diabetes over a short follow-up period of 24 weeks [[]]. However, 9 % of diabetics in the ezetimibe group had their drug regime altered due to hyperglycaemia versus 4 % of the placebo group. Although
ezetimibe 13376 wider interpretation of its results is fraught. In the IMPROVE-IT randomised comparison of additional ezetimibe or placebo for subjects on statins with recent acute coronary syndrome a preliminary report, not yet
ezetimibe 13511 on statins with recent acute coronary syndrome a preliminary report, not yet peer-reviewed, suggests ezetimibe resulted in a small, non-statistically significant, increase in the relative risk of new-onset diabetes
ezetimibe 13884 larger effect on diabetes risk of lifelong inhibition of the genes encoding the molecular targets of ezetimibe : a 2.42 (95 % CI 1.70 to 3.43) odds ratio per mmol/l lower LDL-c. Therefore, longer term data on diabetes
ezetimibe 14011 1.70 to 3.43) odds ratio per mmol/l lower LDL-c. Therefore, longer term data on diabetes risks with ezetimibe treatment are needed to rule out a diabetes risk.FibratesFibrates interact with peroxisome proliferator-activated
ezetimibe 16280 Further studies delineating the mechanisms by which statins cause diabetes are clearly needed. Both ezetimibe and PCSK9 inhibitors lack sufficient clinical trial data to exclude a diabetogenic effect, although,
fenofibrate 6629 limited evidence suggesting bezafibrate may lower diabetes risk but no clear evidence of an effect of fenofibrate in the FIELD trialMixed genetic data on the association of PPAR-alpha SNPs with diabetes: more studies
fenofibrate 14532 FIELD study randomised diabetic subjects not on any statin therapy at baseline (n = 9795) to either fenofibrate or placebo. Over 6 years, the change in HbA1c was negligible regardless of randomisation but formal
niacin 964 In contrast, there is clear evidence of a diabetogenic effect for the now outdated but well-studied niacin . For ezetimibe and fibrates, evidence is scarce but currently broadly unconcerning. For now, the glycemic
niacin 6372 target for Ezetimibe. None as yetNiacin34 % increased risk of new diabetes associated with the use of niacin in meta-analysis of trial dataNo published dataNone since niacin is no longer recommended due to its
niacin 6437 diabetes associated with the use of niacin in meta-analysis of trial dataNo published dataNone since niacin is no longer recommended due to its lack of clinical outcome benefit.FibratesPrior limited evidence
niacin 10267 unlikely that a modest diabetogenic effect would alter treatment decisions [[]•].NiacinThe B vitamin niacin initially showed promise, with a reduction in 17 % reduction in MI seen in results from the Coronary
niacin 10594 was seen in addition to statin therapy [[], []]. As well as the well-recognised flushing effects of niacin , one notable side effect is a worsening of glycemic control. Although early work concluded this effect
niacin 11005 significant effect. Over a 5-year follow-up, in the Coronary Drug Project’s randomised comparison of niacin to placebo, patients with impaired fasting glucose tolerance at baseline progressed to diabetes at a
niacin 11132 with impaired fasting glucose tolerance at baseline progressed to diabetes at a rate of 19.8 % on niacin versus 15.2 % on placebo (HR 1.34 (1.00–1.80)) with a similar (although non-significant) relative
niacin 11376 normal glucose tolerance (HR 1.41 (0.97, 2.05)) [[]]. In the HPS2-THRIVE comparison of the addition of niacin or placebo to those already on statins there was a 55 % increase in serious disturbances in glycemic
niacin 11581 glycemic control (for which many patients were hospitalised), affecting 11.2 % of diabetics assigned to niacin [[]]. Furthermore, there was a 30 % increase in the risk of new-onset diabetes in the treatment group.
niacin 11758 diabetes in the treatment group. Goldie et al. performed a rigorous meta-analysis on the effect of niacin on the risk of new-onset diabetes [[]•]. Overall, they found a 34 % increased risk of new diabetes
niacin 11894 diabetes [[]•]. Overall, they found a 34 % increased risk of new diabetes associated with the use of niacin (although this may be a slight overestimate as trials with no new cases of diabetes were excluded).
niacin 15730 outcomes.ConclusionsIt is striking that both genetic studies and large scale meta-analysis for statins and niacin (the two lipid-lowering therapies for which there is a reasonable body of data) point towards an inverse
niacin 15902 body of data) point towards an inverse link between LDL cholesterol and glycemic control, although niacin also influences HDL-cholesterol levels which may have separate links to diabetes. However, it is not
pravastatin 2840 account for the reduced risk of new-onset diabetes originally seen amongst users of the hydrophilic pravastatin in the pivotal West of Scotland Coronary Prevention Study [[]]. However, this line of argument remains
pravastatin 3013 [[]]. However, this line of argument remains speculative and diabetes risk was clearly elevated in the pravastatin arm of the PROSPER trial [[]]. Secondly, there appear to be downstream ‘on-target’ effects of HMG-CoA
rosuvastatin 1927 increases in the new development of diabetes mellitus [[]]. Individuals receiving maximal doses of rosuvastatin had a 28 % excess rate of diabetes (mainly confined to those with preexisting risk factors) compared
Select Disease Character Offset Disease Term Instance
diabetes mellitus 399 on the adverse glycemic effects of statin therapy. Although the modest increase in the risk of new diabetes mellitus is outweighed by the reduction in cardiovascular events for statins, emerging biochemical and genetic
diabetes mellitus 1864 randomised JUPITER trial that focus turned to modest but significant increases in the new development of diabetes mellitus [[]]. Individuals receiving maximal doses of rosuvastatin had a 28 % excess rate of diabetes (mainly
diabetes mellitus 3788 is emerging evidence of an association between alleles influencing lipid metabolism and the risk of diabetes mellitus . At one extreme, individuals with familial hypercholesterolaemia have a lower incidence of diabetes
diabetes mellitus 3897 mellitus. At one extreme, individuals with familial hypercholesterolaemia have a lower incidence of diabetes mellitus compared to unaffected family members—despite early and aggressive treatment with statins [[]]. Broader
metabolic syndrome 7987 amongst participants in a randomised trial against standard care who had preexisting dysglycaemia or metabolic syndrome over 52 weeks [[]]. In a recent meta-analysis, we did not find any significant difference in lipid

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