Statins and risk for new-onset diabetes mellitus

Yoon, Dukyong; Sheen, Seung Soo; Lee, Jimin; Choi, Yong Jun; Park, Rae Woong; Lim, Hong–Seok

doi:10.1097/md.0000000000005429

Cited by 27 publications

(13 citation statements)

References 37 publications

(60 reference statements)

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“…It is not to be missed, that the medical information on statin-induced diabetes is contradictory in some cases. For example, in [98] rosuvastatin was described as less harmful for the glucose homeostasis than simvastatin. The same observation was deposited in SIDER (see Table A in S1 File).…”

Section: Resultsmentioning

confidence: 99%

Drug-induced diabetes type 2: In silico study involving class B GPCRs

et al. 2019

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A disturbance of glucose homeostasis leading to type 2 diabetes mellitus (T2DM) is one of the severe side effects that may occur during a prolonged use of many drugs currently available on the market. In this manuscript we describe the most common cases of drug-induced T2DM, discuss available pharmacotherapies and propose new ones. Among various pharmacotherapies of T2DM, incretin therapies have recently focused attention due to the newly determined crystal structure of incretin hormone receptor GLP1R. Incretin hormone receptors: GLP1R and GIPR together with the glucagon receptor GCGR regulate food intake and insulin and glucose secretion. Our study showed that incretin hormone receptors, named also gut hormone receptors as they are expressed in the gastrointestinal tract, could potentially act as unintended targets (off-targets) for orally administrated drugs. Such off-target interactions, depending on their effect on the receptor (stimulation or inhibition), could be beneficial, like in the case of incretin mimetics, or unwanted if they cause, e.g., decreased insulin secretion. In this in silico study we examined which well-known pharmaceuticals could potentially interact with gut hormone receptors in the off-target way. We observed that drugs with the strongest binding affinity for gut hormone receptors were also reported in the medical information resources as the least disturbing the glucose homeostasis among all drugs in their class. We suggested that those strongly binding molecules could potentially stimulate GIPR and GLP1R and/or inhibit GCGR which could lead to increased insulin secretion and decreased hepatic glucose production. Such positive effect on the glucose homeostasis could compensate for other, adverse effects of pharmacotherapy which lead to drug-induced T2DM. In addition, we also described several top hits as potential substitutes of peptidic incretin mimetics which were discovered in the drug repositioning screen using gut hormone receptors structures against the ZINC15 compounds subset.

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Section: Resultsmentioning

confidence: 99%

Drug-induced diabetes type 2: In silico study involving class B GPCRs

et al. 2019

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“…Statins are known to be associated with a higher risk of NOD 25 – 29 . In the present study, the sensitivity analysis showed that statins had no impact on NOD.…”

Section: Discussionmentioning

confidence: 99%

Lipid levels and new-onset diabetes in a hypertensive population: the China Stroke Primary Prevention Trial

Yang

et al. 2017

Sci Rep

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This study aimed to provide insights into the relationship between lipid levels and new-onset diabetes (NOD) in 14,864 Chinese hypertensive patients without diabetes (6056 men and 8808 women) aged 45–75 years from the China Stroke Primary Prevention Trial (CSPPT, led by Nanfang Hospital, Guangzhou, China). NOD (defined as fasting plasma glucose (FPG) ≥ 7.0 mmol/L at the end of study or self-reported physician diagnosis of diabetes or self-reported use of hypoglycemic agents during follow-up) was analyzed using multivariate analysis. Follow-up was censored on August 24, 2014. Among the 14,864 subjects, 1615 developed NOD (10.9%, men = 10.8% and women = 10.9%). Increased triglycerides (TG) [odds ratio (OR) = 1.18; 95% confidence interval (CI): 1.13–1.25, P < 0.001], TG/HDL (OR = 1.12; 95%CI: 1.08–1.17, P < 0.001), and decreased high density lipoprotein (HDL) (OR = 0.79; 95%CI: 0.67–0.93, P = 0.005) were associated with NOD, independently from age, gender, body mass index, clinical center, systolic blood pressure, diastolic blood pressure, FPG, smoking, and drinking. Compared to subjects with the methylenetetrahydrofolate reductase (MTHFR) 677 CC and TT genotypes, those with the CT genotype had a higher risk of NOD (OR = 1.54; 95%CI: 1.30–1.81, P for interaction = 0.044) in subjects with high TG. These results suggested that TG and TG/HDL were independent risk factors for NOD in this Chinese hypertensive population. HDL was a protective factor for NOD.

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“…Previous studies have provided controversial findings regarding whether pitavastatin is associated with lower risk of NODM than atorvastatin and rosuvastatin [ 8 , 9 , 13 , 15 , 30 , 31 ]. Although Vallejo-Vaz et al proposed a neutral effect of pitavastatin on the risk of NODM through a meta-analysis of randomized control trials, the included trials might have included relatively small sample sizes and short follow-up periods, which might have limited the diabetogenic effect of statins [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

“…Notably, Kim et al studied the Korean population and suggested the lowest rate of progression from non-diabetes to prediabetes in the pitavastatin group during the 4-year follow-up period [ 30 ]. The baseline characteristics and comorbidities of the included population in each study might have led to the discrepancy in the results [ 8 , 9 , 13 , 30 ]. In our study with a 4-year follow-up period, we enrolled 8337 patients.…”

Section: Discussionmentioning

confidence: 99%

“…Pitavastatin was proposed to have the highest risk of NODM compared with rosuvastatin, atorvastatin, pravastatin, and simvastatin in a retrospective cohort study, with a follow-up period of 5 years [ 8 ]. However, in a 19-year retrospective cohort study, pitavastatin was associated with a lower HR of NODM than atorvastatin, fluvastatin, pravastatin, rosuvastatin, and simvastatin, without statistical significance [ 13 ]. Such evidence indicates the controversial effects of individual statins on the risk of NODM.…”

Section: Introductionmentioning

confidence: 99%

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Effects of Pitavastatin, Atorvastatin, and Rosuvastatin on the Risk of New-Onset Diabetes Mellitus: A Single-Center Cohort Study

et al. 2020

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Statins constitute the mainstay treatment for atherosclerotic cardiovascular disease, which is associated with the risk of new-onset diabetes mellitus (NODM). However, the effects of individual statins on the risk of NODM remain unclear. We recruited 48,941 patients taking one of the three interested statins in a tertiary hospital between 2006 and 2018. Among them, 8337 non-diabetic patients taking moderate-intensity statins (2 mg/day pitavastatin, 10 mg/day atorvastatin, and 10 mg/day rosuvastatin) were included. The pitavastatin group had a higher probability of being NODM-free than the atorvastatin and rosuvastatin groups during the 4-year follow-up (log-rank test: p = 0.038). A subgroup analysis revealed that rosuvastatin had a significantly higher risk of NODM than pitavastatin among patients with coronary artery disease (CAD) (adjusted HR [aHR], 1.47, 95% confidence interval [CI], 1.05–2.05, p = 0.025), hypertension (aHR, 1.26, 95% CI, 1.00–1.59, p = 0.047), or chronic obstructive pulmonary disease (COPD) (aHR, 1.74, 95% CI, 1.02–2.94, p = 0.04). We concluded that compared with rosuvastatin, reduced diabetogenic effects of pitavastatin were observed among patients treated with moderate-intensity statin who had hypertension, COPD, or CAD. Additional studies are required to prove the effects of different statins on the risk of NODM.

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Statins and risk for new-onset diabetes mellitus

Abstract: Supplemental Digital Content is available in the text

Cited by 27 publications

References 37 publications

Drug-induced diabetes type 2: In silico study involving class B GPCRs

Drug-induced diabetes type 2: In silico study involving class B GPCRs

Lipid levels and new-onset diabetes in a hypertensive population: the China Stroke Primary Prevention Trial

Effects of Pitavastatin, Atorvastatin, and Rosuvastatin on the Risk of New-Onset Diabetes Mellitus: A Single-Center Cohort Study

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