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Keywords:

  • diabetes;
  • pharmacoepidemiology;
  • prescribing database;
  • retrospective cohort;
  • statins

Abstract

  1. Top of page
  2. Abstract
  3. What Is Already Known About This Subject
  4. What This Study Adds
  5. Introduction
  6. Methods
  7. Results
  8. Discussion
  9. Competing Interests
  10. References

Aims

(i) To examine the incidence of new onset treated diabetes in patients treated with different types of statins and (ii) the relationship between the duration and dose of statins and the subsequent development of new onset treated diabetes.

Methods

A retrospective cohort study was performed using the Irish Health Services Executive Primary Care Reimbursement Services national pharmacy claims database. Individuals who received any medicines were identified from January 2001 to January 2009 (n = 1 235 671). Patients newly treated with statins from 1 January 2002 to 31 December 2007 were identified (n = 239 628). Cases were identified as individuals newly treated with antidiabetic medication (n = 38 503). Adjusted hazards ratios (HR) with 95% confidence intervals (CI) were calculated to examine the association between statins (any vs. none) and time to new onset treated diabetes using Cox proportional hazard regression. The dose and duration response relationship between statins and new onset treated diabetes was examined using restricted spline functions to assess the linearity of the relationship.

Results

Statin use was associated with an increased risk of new onset treated diabetes (HR = 1.18, 95% CI 1.15, 1.22). Increased risk of new onset treated diabetes was found with rosuvastatin (HR = 1.41, 95% CI 1.31, 1.52), atorvastatin (HR = 1.23, 95% CI 1.19, 1.27) and simvastatin (HR = 1.15, 95% CI 1.05, 1.25). There were statistically significant overall dose and duration effects for all statins, excepting fluvastatin, which only demonstrated a duration effect.

Conclusion

An increased risk of new onset treated diabetes was found in those treated with statins showing significant duration and dose effect. Further study is required to confirm this association.


What Is Already Known About This Subject

  1. Top of page
  2. Abstract
  3. What Is Already Known About This Subject
  4. What This Study Adds
  5. Introduction
  6. Methods
  7. Results
  8. Discussion
  9. Competing Interests
  10. References
  • Statins are used for primary and secondary prevention in patients at high risk of cardiovascular disease.
  • Recent meta-analyses of randomized controlled trials have shown an increased risk of new onset diabetes with statin therapy.
  • The potential association of new onset diabetes with statin therapy in the general primary care population requires further examination.

What This Study Adds

  1. Top of page
  2. Abstract
  3. What Is Already Known About This Subject
  4. What This Study Adds
  5. Introduction
  6. Methods
  7. Results
  8. Discussion
  9. Competing Interests
  10. References
  • We found an association between new onset treated diabetes in those prescribed statins in a primary care population.
  • The increase in new onset treated diabetes was found with monotherapy of rosuvastatin, simvastatin and atorvastatin compared with those without a statin prescription.
  • There were statistically significant overall dose and duration effects for all statins, except fluvastatin which only demonstrated a duration effect.

Introduction

  1. Top of page
  2. Abstract
  3. What Is Already Known About This Subject
  4. What This Study Adds
  5. Introduction
  6. Methods
  7. Results
  8. Discussion
  9. Competing Interests
  10. References

HMG-CoA reductase inhibitors or statins reduce LDL cholesterol by inhibition of cholesterol synthesis in the liver. Statins also possess other properties beyond lipid lowering, referred to as pleiotropic effects, such as stabilization of atherosclerotic plaques, improvement of vascular endothelial function, reduction of vascular inflammation, reduction of platelet aggregability and anti-oxidant effects [1]. The Joint 2012 European guideline on cardiovascular prevention has advocated the use of statins for dyslipidaemia as part of the prevention of cardiovascular disease in patients at high risk of cardiovascular disease, including those with diabetes [2].

The prescribing of statins in Ireland is amongst the highest in Europe [3, 4]. The prevalence of their use in those aged between 55 to 74-years-old was approximately 75% in women and 77% in men for secondary cardiovascular prevention, and for primary cardiovascular prevention was 11% in men and 16% in women in the same age group in 2006 [5]. In 2008, atorvastatin was the second most frequently dispensed medication in the Irish population and accounted for the largest expenditure on medications by the Irish health services. The cost borne by the Irish government for all statins (ingredient cost only) in 2008 was a staggering €141 million [6]. This translated into significantly better lipid control in the Irish population compared with other European countries as demonstrated in the EUROASPIRE III study [3].

Statins are associated with some adverse effects such as myopathy, elevated liver enzymes, peripheral neuropathy and, rarely, rhabdomyolysis [7]. Recent interest has emerged on the risk of new onset diabetes in patients receiving statins. Post hoc analysis of the West of Scotland Coronary Prevention Study (WOSCOPS) in 2001 was the first that highlighted the relationship between statins and diabetes and showed that pravastatin was associated with a 30% reduced risk of new onset diabetes compared with placebo (OR = 0.70) [8]. In contrast, the results from the Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER), published in 2008, showed that patients assigned to rosuvastatin therapy had an increased risk of new onset diabetes compared with placebo (RR = 1.25) [9]. Another randomized controlled trial (RCT) examining an elderly population, the Pravastatin in Elderly individuals at risk of vascular disease (PROSPER) study, showed that pravastatin was also associated with an increased risk of new onset diabetes compared with placebo (OR = 1.32) [10].

Recent meta-analyses of RCTs have been performed on the relationship between statins and new onset diabetes and three of these meta-analyses demonstrated that statins were associated with a slightly increased risk of new onset diabetes [11-14]. Rajpathak et al. performed a meta-analysis of six RCTs of statins and found a significantly increased risk of new onset diabetes with statin therapy (OR = 1.13). However, when this meta-analysis included the WOSCOPS trial, the risk of new onset diabetes was no longer significant (OR = 1.06). This meta-analysis did not examine the differential risk of new onset diabetes with different types of statin [11]. Sattar et al. performed another meta-analysis of thirteen RCTs and found a significant increased risk of new onset diabetes with statins (OR = 1.09) with a similar risk observed between the different types of statin [12]. A more recent meta-analysis by Preiss et al. which included five RCTs demonstrated a higher risk of new-onset diabetes with intensive dose compared with moderate dose of statin therapy [13]. On the contrary, a meta-analysis performed by Coleman et al. did not find a significant risk of new onset diabetes with statins (RR = 1.03) [14]. The slight differences in the risk of new onset diabetes between these meta-analyses may be accounted for by differences in sample sizes and possible selection bias. These meta-analyses also differed in the criteria taken to determine new onset diabetes, the confounding factors included and the statistical methods used.

A retrospective population based case control study performed using the UK General Practice Research Database (GPRD) post the WOSCOPS findings did not find any significant relationship between statins and new onset diabetes [15]. On the other hand, a more recent population based study using data from 153 840 postmenopausal women enrolled in the Women's Health Initiative (WHI) study in the US showed an increased risk of new onset diabetes in this population [16]. With such high prescribing of statins in the Irish population and the increasing prevalence of diabetes [17], the risk of new onset diabetes following statin use in this population requires consideration. This study was performed to examine the association between statins and the subsequent prescription of antidiabetic medications (used as a surrogate for the development of new onset treated diabetes) in a retrospective cohort study in the Irish primary care population. The effect of different types of statins and their duration and dose−response relationship on the new onset treated diabetes was examined using a large national pharmacy claims database.

Methods

  1. Top of page
  2. Abstract
  3. What Is Already Known About This Subject
  4. What This Study Adds
  5. Introduction
  6. Methods
  7. Results
  8. Discussion
  9. Competing Interests
  10. References

A retrospective cohort study was performed using the Irish Health Service Executive – Primary Care Reimbursement Services (HSE-PCRS) national pharmacy claims database. The HSE PCRS database records all prescriptions dispensed by pharmacists throughout Ireland for claims purposes from a number of different reimbursement schemes. For the purpose of this study, patients under the General Medical Services (GMS) Scheme were selected. The eligibility for this scheme is means tested for those under 70-years-old and free for all 70-years-old and over from July 2001 until December 2008. The scheme is, therefore, over represented by females, socio-economically deprived patients and the elderly. The scheme covers approximately one third of the total population in Ireland, approximately 1.35 million individuals in 2008 [6]. Medications dispensed are recorded using the World Health Organization (WHO) Anatomical Therapeutic Classification (ATC) code. In addition, each dispensing record includes basic demographic information such as age group, gender and region of residence. Clinical diagnosis is, however, not recorded in the database.

Study cohort

Patients who received monotherapy of the different types of statin from 1 January 2002 to 31 December 2007 were identified from the cohort (n = 239 628). The statins included in the study were atorvastatin (n = 120 307), pravastatin (n = 41 899), rosuvastatin (n = 19 888), simvastatin (n = 11 458) and fluvastatin (n = 3125). Duration of exposure to statins was examined according to the number of months for which the patients were treated with statins. The total cumulative dosage of statin dispensed over the study period was determined using the defined daily doses (DDD) according to WHO methodology. The DDD is assumed to be the average recommended daily dose for a drug used for its main indication in adults [18]. DDD is a unit of measurement and thus does not necessarily reflect recommended or prescribed dose. A DDD is equivalent to 10 mg atorvastatin, 20 mg pravastatin, 10 mg rosuvastatin, 15 mg simvastatin and 40 mg fluvastatin. All patients initiated on statins were followed up until their first prescription of any antidiabetic medications (oral hypoglycaemics or insulin) or until 31 January 2009 in those not receiving antidiabetic medication. Patients who did not receive statins during the study period were considered as a control group (n = 996 043) and were followed up until they received antidiabetic agents or until 31st January 2009.

Covariates

Oral corticosteroids, thiazide diuretics, β-adrenoceptor blockers and antipsychotics were considered potential confounders as previous studies have shown some association of these agents with new onset diabetes [19]. Patients prescribed nitrate therapies were considered to have ischaemic heart disease. Nitrate prescribing has been shown to be a useful surrogate marker for coronary heart disease with a sensitivity of approximately 73% and specificity of 96% [20]. In addition, those prescribed antihypertensive agents and other lipid lowering drugs were also identified, ezetimibe, fibrates, nicotinic acid and omega-3 triglycerides.

Statistical analysis

Univariate analyses were performed on possible covariates to examine the association between each co-prescribed medication of interest and new onset treated diabetes. The baseline characteristics of patients (age, gender) and risk of treated diabetes with covariates are presented in Table 1. Medications having significant relationship with new onset treated diabetes were included for adjustment in the final statistical analysis. Cox proportional hazard regression was used to calculate the hazard ratio (HR with 95% confidence interval (CI)) of new onset treated diabetes in the cohort treated with statins compared with the general population cohort without statins, adjusting for age groups, gender and covariates.

Table 1. Baseline characteristics of patients included in retrospective cohort study with univariate analysis of risk of new onset diabetes presented as HR with 95% CI
Patient characteristics (n = 197 138)TotalNumber with diabetes (%)HR (95% CI), P
  1. ***P < 0.0001. †Reference category males. ‡Reference category age 25–44 years. §Reference category cohort not prescribed diabetogenic agents. ¶Reference category cohort without cardiovascular comorbidities. ††Reference category cohort not prescribed lipid lowering agents. NS not significant.

GenderFemales vs. males749 09619 324 (2.6%)1.02 (0.99, 1.04), NS
Age groups (years)25–44500 3057 672 (1.5%)
45–64337 00312 472 (3.7%)0.96 (0.94, 1.00), NS
≥65398 36318 662 (4.7%)1.14 (1.11, 1.16)***
Diabetogenic agents§Antipsychotics266 8076 721 (2.5%)1.24 (1.21, 1.28)***
Corticosteroids366 53110 179 (2.8%)0.77 (0.75, 0.80)***
Cardiovascular comorbiditiesHypertension528 86121 391 (4.0%)1.19 (1.17, 1.22)***
IHD56 7562 799 (4.8%)1.14 (1.10, 1.19)***
Obesity35 5381 552 (4.3%)1.31 (1.23, 1.39)***
Other lipid lowering agents††Ezetimibe8 475309 (3.6%)1.67 (1.47, 1.88)***
Omega-37 099192 (2.7%)1.70 (1.44, 2.00)***
Fibrates2 149153 (7.1%)1.24 (1.08, 1.44) P = 0.003
Nicotinic acid798179 (8.5%)1.35 (1.01, 1.80) P = 0.04

The dose and duration response relationship between statins and new onset treated diabetes was examined using restricted spline functions (with three knots at 5%, 50% and 95% percentiles) to assess the linearity or otherwise of the relationship [21]. A SAS macro was obtained from the authors to fit the models with restricted spline functions. For any associations found to be linear, a continuous term for dose and duration effect was included in the Cox proportional hazards model. For the purpose of presenting hazard ratios (HR) the dose is presented per 30 DDD (equivalent to 1 month). If the dose−response relationship was found to be non-linear the odds ratio for new onset treated diabetes was calculated at the following dosage levels: 180 DDDs, 360 DDDs, 720 DDDs and at the threshold (if applicable) for the last category. If the duration association was non-linear the HR was calculated at the following duration intervals: 6 months, 12 months, 24 months and at the threshold for the last category. Interaction effects between dose and duration effects were tested in the models. Analysis was performed using the %RCSREG macro [21] and PROC TPHREG command in SAS version 9.1 (SAS Institute Inc, Cary). Significance at P < 0.05 is assumed.

Results

  1. Top of page
  2. Abstract
  3. What Is Already Known About This Subject
  4. What This Study Adds
  5. Introduction
  6. Methods
  7. Results
  8. Discussion
  9. Competing Interests
  10. References

During the study period 19% of patients in the cohort received statins with 6% receiving more than 24 months of statin therapy. 5.9% (n = 9253) of patients treated with statins were initiated on antidiabetic medications compared with 2.5% (n = 25 152) in the cohort not treated with any statins. An increased risk of new onset treated diabetes was found in those receiving statins (HR (adjusted) = 1.20, 95% CI 1.17, 1.23) compared with those receiving none. A significant risk of new onset diabetes was observed with monotherapy of atorvastatin, rosuvastatin and simvastatin (Table 2). The highest risk of new onset treated diabetes in this cohort was observed with monotherapy of rosuvastatin (HR (adjusted) = 1.42, 95% CI 1.33, 1.52). There was a significant linear association between duration and cumulative dose (DDDs) of treatment and new onset treated diabetes with all types of statins (P < 0.0001) in this cohort.

Table 2. Frequency and risk of new onset diabetes with different types of statins (unadjusted and adjusted HR with 95% CI)
StatinsTotalNumber with diabetes (n, %)UnadjustedAdjusted
HR, 95% CI, PHR*, 95% CI, P
  1. *HR with 95% CI adjusted for gender, age groups, prescriptions of oral corticosteroids, antipsychotics, antihypertensives, medications for ischaemic heart disease, anti-obesity and other lipid modifying agents. †Significant linear trend test for duration adjusted for covariates and risk of new onset diabetes (P < 0.05). ‡Significant linear trend test for dose (as DDDs) adjusted for covariates and risk of new onset diabetes (P <0.05). ***P < 0.0001; NS not significant.

All statins195 66311 591 (5.9%)1.22 (1.20, 1.25)***1.20 (1.17, 1.23)***
Atorvastatin120 3075 608 (4.7%)1.28 (1.25, 1.32)***1.25 (1.21, 1.28)***
Pravastatin41 8992 729 (6.5%)1.02 (0.98, 1.06), NS1.02 (0.98, 1.06), NS
Rosuvastatin19 888967 (4.9%)1.46 (1.37, 1.56)***1.42 (1.33, 1.52)***
Simvastatin11 458726 (6.3%)1.16(1.08, 1.25) P = 0.0011.14 (1.06, 1.23) P = 0.0005
Fluvastatin3 125220 (7.0%)1.09 (0.95, 1.24) NS1.04 (0.91, 1.18) NS

Using the analysis of restricted spline functions and adjusting for the covariates, the dose and duration effect of simvastatin was significantly linearly associated with new onset treated diabetes for both dose (HR = 1.01, 95% CI 1.01, 1.02 per 30 DDD unit increase, P < 0.0001) and duration of simvastatin (HR = 1.02, 95% CI 1.01, 1.03, P < 0.0001 for duration). Similarly for fluvastatin there was a significant linear dose response effect (HR = 1.02, 95% CI 1.01, 1.03, P < 0.0001), but non-significant linear effect of duration (HR = 1.02, 95% CI 1.00, 1.01, P = 0.067). For pravastatin, there was a significant linear duration effect (HR = 1.03, 95% CI 1.02, 1.03, P < 0.0001) but non-linear dose response effect (P = 0.0003 for non-linear effect; HR = 1.11, 95% CI 1.09, 1.14 for 180 DDDs; HR = 1.23, 95% CI 1.17, 1.29 for 360 DDDs; HR = 1.47, 95% CI 1.36, 1.60 for 720 DDDs and HR = 2.50, 95% CI 1.17, 2.85 for 2700 DDDs (threshold)). For atorvastatin there was a significant linear duration effect (HR = 1.03, 95% CI 1.02, 1.03, P < 0.0001) and non-linear dose−response effect (P < 0.0001 for non-linear effect; HR = 1.10, 95% CI 1.09, 1.11 for 180 DDDs; HR = 1.22, 95% CI 1.19, 1.24 for 360 DDDs; HR = 1.46, 95% CI 1.41, 1.51 for 720 DDDs and HR = 2.68, 95% CI 2.45, 2.93 for 4500 DDDs (threshold)). There was a similar linear duration (HR = 1.02, 95% CI 1.01, 1.02, P < 0.0001) and non-linear dose response effect for rosuvastatin (P < 0.0001 for non-linear effect; HR = 1.66, 95% CI 1.50, 1.84 for 180 DDDs; HR = 2.61, 95% CI 2.17, 3.14, for 360 DDDs; HR = 4.42, 95% CI 3.44, 5.67 for 720 DDDs and HR = 5.1, 95% CI 3.85, 6.82 for 1020 DDDs (threshold)). Interaction tests between dose and duration effects were tested but none shown to be significant.

Discussion

  1. Top of page
  2. Abstract
  3. What Is Already Known About This Subject
  4. What This Study Adds
  5. Introduction
  6. Methods
  7. Results
  8. Discussion
  9. Competing Interests
  10. References

An increased risk of new onset treated diabetes was found in those treated with rosuvastatin, atorvastatin and simvastatin compared with those without statins in this retrospective cohort study using a pharmacy claims database. There was also a significant linear association between duration as well as linear and non-linear associations with dose of treatment with these statins. There were statistically significant overall dose and duration effects for all statins, except a duration effect for fluvastatin, possibly due to smaller numbers of patients.

Compared with the present study a population study in the UK using the GPRD did not find a significant relationship between current statin users and new onset diabetes (OR = 1.1, 95% CI 0.8, 1.4) [15]. Only simvastatin and pravastatin were examined individually due to insufficient number of patients on other types of statin therapy at the time of the study and no significant relationship between prescription of these statins and new onset diabetes was found. The GPRD study also did not find any evidence of a relationship between new onset diabetes and cumulative prescription or duration of statins. Unlike the present study, only a small number of patients were prescribed long term statins at the time the UK GPRD case control study was carried out [15]. The findings from this population based study, however, were similar to findings from the WHI study in the US [16]. The greater risk observed in the WHI study (HR = 1.48, 95% CI 1.38, 1.59) compared with the present study may be due to the different population being examined. The WHI included only post-menopausal women while the present study included adults of all ages and thus the findings are more generalizable to the population. Similar to the WHI study, the findings from the present study also suggest that the association between statins and new onset diabetes is a medication class effect [16].

Although three meta-analyses of RCTs showed a significant increased risk of new onset diabetes with statins [11-13], the effect size (odds ratio) was not as strong as that suggested by the present observational and population based study. These may be due to the differences in the selection criteria and the medical management received in those enrolled in the RCT populations compared with our study population. The criteria to diagnose new onset diabetes also differed. While these meta-analyses used a fasting glucose value to classify a person as having diabetes, the present study and the WHI study included only treated diabetes. As no clinical diagnosis is available in the HSE-PCRS database, some patients with lifestyle controlled diabetes may have been misclassified as not having diabetes and may have progressed to treated diabetes during the study period. These patients may have been prescribed statins early on as part of a primary or secondary cardiovascular preventative strategy.

A few hypotheses have emerged to explain the mechanisms by which statins may induce new onset diabetes. Sampson et al. proposed that the effects of statins on new onset diabetes may centre on altered insulin secretion rather than insulin sensitivity via multiple mechanisms that compromise the functions of pancreatic beta cells [22]. The hypothetical paradigm proposed involves (i) inhibition of intracellular glucose arrival via glucose transporter (GLUT2) which initiates the cascades for insulin secretion, (ii) inhibition of glucokinase by plasma derived cholesterol which is in abundance when de novo synthesis of cholesterol is inhibited, (iii) reduction in ATP production due to suppression of ubiquinine (CoQ10) leading to inhibition of insulin secretions, (iv) suppression of isoprenoid synthesis causing down-regulation of the glucose transport system (GLUT4) which is important in glucose uptake, (v) the pro-inflammatory and oxidative effects of plasma derived cholesterol and (vi) induction of beta cell apoptosis due to cytokine-induced over production of nitric oxide [22].

The present study showed that the different statins were associated with a differing risk of new onset diabetes. A meta-analysis of sixteen RCTs by Baker et al. found a differential effect of statin types on insulin sensitivity [23]. Pravastatin was associated with significantly improved insulin sensitivity while simvastatin was associated with significantly worse insulin sensitivity [21]. Statin therapy has also been found to induce insulin resistance via inhibition of isoprenoid biosynthesis, a precursor for cholesterol formation. Differences between different types of statin may also be explained by the water solubility of the different statins. Lipid soluble statins such as simvastatin and atorvastatin are taken up by pancreatic cells and adipocytes and thus may attenuate insulin action by interfering with isoprenoid biosynthesis compared with the more highly water soluble statins such as pravastatin [24, 25]. However, this would not explain the differential effects between rosuvastatin and pravastatin observed in this study as rosuvastatin, like pravastatin is a water soluble statin. In comparison with other statins, rosuvastatin has been shown to be more potent and efficacious than atorvastatin, simvastatin and atorvastatin while sharing the same adverse effects as other types of statins [26, 27].

It is possible that the relationship between statins and new onset treated diabetes, as observed in this study, is due to the effects of hyperlipidaemia. The increased risk of new onset diabetes was also observed with other lipid modifying agents such as ezetimibe, omega-3 triglycerides and fibrates in this cohort study and this may favour confounding by indication. However, the meta-analysis by Sattar and colleagues has shown that the increased risk of new-onset diabetes observed in those treated with statins is independent of lipid concentrations [12].

The question is; how can the risk of new onset diabetes in those prescribed statins be compared with the overall reduction in cardiovascular events offered by statins? A recent editorial suggested that prescribers should weigh up the small risk of developing diabetes compared with the greater cardiovascular protection conferred by statins in patients at risk of cardiovascular disease [28]. However, prescribers may also need to consider screening for diabetes as well as other safety measures in those prescribed statins [26]. A meta-analysis on statins performed by the Cholesterol Treatment Trialists (CTT) collaborators using data from 90 056 participants involved in 14 large RCTs demonstrated a proportional reduction in all-cause mortality by 12% and a proportional reduction of major vascular events (major coronary events, coronary revascularization and stroke) by approximately one fifth for every mmol l−1 reduction of LDL cholesterol over a 5 year period [29]. Another meta-analysis by the same group performed on a cohort of 18 686 participants with diabetes treated with statins from the same 14 RCTs showed a similar reduction of all cause mortality (9%) and a one fifth reduction in major vascular events for every mmol l−1 LDL cholesterol reduction [30]. A recent population based cohort study using a computerized database of 6697 patients with diabetes in Tayside, Scotland demonstrated that statins significantly reduced cardiovascular events when used as primary prevention (HR = 0.61, 95% CI 0.57, 0.66) and secondary prevention (HR = 0.59, 95% CI 0.47, 0.76) per mmol of total cholesterol reduction [31].

On the other hand, a systemic review by de Lorgeril et al. suggested that cholesterol lowering drugs such as statins and fibrates do not have any significant effect on cardiovascular complications and overall mortality benefit [32]. However, only two RCTs on statins satisfied the criteria for inclusion in the analysis of this systemic review, the German Diabetes and Dialysis Study (4D) and the Atorvastatin Study for Prevention of Coronary Heart Disease Endpoints in Non Insulin Dependent Diabetes Mellitus (ASPEN). The authors also highlighted the fact that the meta-analysis by CTT collaborators was limited by the exclusion of the 4D and ASPEN RCTs in patients with diabetes and the inclusion of data from a non-randomized subgroup of patients with diabetes [32]. Of note, most authors involved in the meta-analyses on statins [11-14, 28-30] have conflicts of interest with pharmaceutical companies marketing statins.

In conclusion, we found a significant association between new onset treated diabetes in those treated with statin therapy. This was associated with increased duration and dose of treatment suggesting a possible biologically plausible effect. Further prospective studies are required to examine this association in order to prove a possible causal relationship.

Competing Interests

  1. Top of page
  2. Abstract
  3. What Is Already Known About This Subject
  4. What This Study Adds
  5. Introduction
  6. Methods
  7. Results
  8. Discussion
  9. Competing Interests
  10. References

DW has been reimbursed by Pfizer, manufacturer of atorvastatin, for attending a conference and BMS, manufacturer of pravastatin, for a consultancy service.

We would like to thank the HSE-PCRS for providing the database in which this study is based. We would also like to acknowledge the late Professor John Feely who contributed his ideas to this work.

References

  1. Top of page
  2. Abstract
  3. What Is Already Known About This Subject
  4. What This Study Adds
  5. Introduction
  6. Methods
  7. Results
  8. Discussion
  9. Competing Interests
  10. References
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