Evidence of heterogeneity in statin-associated type 2 diabetes mellitus risk: A meta-analysis of randomized controlled trials and observational studies

Engeda, Joseph C.; Stackhouse, Ashlyn; White, Mary; Rosamond, Wayne D.; Lhachimi, Stefan K.; Lund, Jennifer L.; Keyserling, Thomas C.; Avery, Christy L.

doi:10.1016/j.diabres.2019.04.005

Cited by 12 publications

(20 citation statements)

References 49 publications

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“…primary and secondary CVD prevention) reported a 9 to 55% increased risk of T2DM in statin users compared with statin non-users [ 75 – 77 ]. In a recent meta-analysis/meta-regression with more than 4 million participants (statins vs no statins) aged ≥ 30 years, older participants were associated with a decreased risk of T2DM (RR 0.79 [95% CI 0.63–0.98] per 10-year older) compared with younger participants [ 76 ]. The reported increase in statin-associated T2DM risk is mainly evident in participants who already are at a high risk to acquire DM (e.g., people with other elements of the metabolic syndrome) [ 75 , 78 ].…”

Section: Discussionmentioning

confidence: 99%

Association of statin use in older people primary prevention group with risk of cardiovascular events and mortality: a systematic review and meta-analysis of observational studies

Awad

Mohammed

Zaki

et al. 2021

BMC Med

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Background Current evidence from randomized controlled trials on statins for primary prevention of cardiovascular disease (CVD) in older people, especially those aged > 75 years, is still lacking. We conducted a systematic review and meta-analysis of observational studies to extend the current evidence about the association of statin use in older people primary prevention group with risk of CVD and mortality. Methods PubMed, Scopus, and Embase were searched from inception until March 18, 2021. We included observational studies (cohort or nested case-control) that compared statin use vs non-use for primary prevention of CVD in older people aged ≥ 65 years; provided that each of them reported the risk estimate on at least one of the following primary outcomes: all cause-mortality, CVD death, myocardial infarction (MI), and stroke. Risk estimates of each relevant outcome were pooled as a hazard ratio (HR) with a 95% confidence interval (CI) using the random-effects meta-analysis model. The quality of the evidence was rated using the GRADE approach. Results Ten observational studies (9 cohorts and one case-control study; n = 815,667) fulfilled our criteria. The overall combined estimate suggested that statin therapy was associated with a significantly lower risk of all-cause mortality (HR: 0.86 [95% CI 0.79 to 0.93]), CVD death (HR: 0.80 [95% CI 0.78 to 0.81]), and stroke (HR: 0.85 [95% CI 0.76 to 0.94]) and a non-significant association with risk of MI (HR 0.74 [95% CI 0.53 to 1.02]). The beneficial association of statins with the risk of all-cause mortality remained significant even at higher ages (> 75 years old; HR 0.88 [95% CI 0.81 to 0.96]) and in both men (HR: 0.75 [95% CI: 0.74 to 0.76]) and women (HR 0.85 [95% CI 0.72 to 0.99]). However, this association with the risk of all-cause mortality remained significant only in those with diabetes mellitus (DM) (HR 0.82 [95% CI 0.68 to 0.98]) but not in those without DM. The level of evidence of all the primary outcomes was rated as “very low.” Conclusions Statin therapy in older people (aged ≥ 65 years) without CVD was associated with a 14%, 20%, and 15% lower risk of all-cause mortality, CVD death, and stroke, respectively. The beneficial association with the risk of all-cause mortality remained significant even at higher ages (> 75 years old), in both men and women, and in individuals with DM, but not in those without DM. These observational findings support the need for trials to test the benefits of statins in those above 75 years of age.

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Section: Discussionmentioning

confidence: 99%

Association of statin use in older people primary prevention group with risk of cardiovascular events and mortality: a systematic review and meta-analysis of observational studies

Awad

Mohammed

Zaki

et al. 2021

BMC Med

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“…Unlike the statin-ASCVD RRs, for which we only used published estimates from randomized controlled trials (RCTs), we considered meta-analytic estimates from RCTs and observational studies when quantifying statin-associated T2D risk: RR = 1.11 (RCTs only), RR = 1.32 (RCT and observational study pooled), and RR = 1.55 (observational studies only). This decision was motivated by previous reports documenting the potential for industry-funded RCTs to underreport adverse drug reactions [15,32], the observation that confounding by factors that affect treatment assignment (i.e., "confounding by indication") is less likely in studies of adverse drug reactions [33], and the average shorter duration (2.6 years) of RCTs compared to observational studies [15].…”

Section: Plos Medicinementioning

confidence: 99%

“…Heterogeneity by sex in age-specific ASCVD incidence rates also is long-described [43], which could further decrease the net benefits of statin therapy for ASCVD reduction. Interestingly, available studies also support the potential for net harms to be greater in females than males [15,16,44,45]. For example, the Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial reported a 50% increase in physicianreported T2D in females compared to males, corresponding to an estimated 11 incident T2D diagnoses per 1,000 females taking statins over 1.9 years [16].…”

Section: Plos Medicinementioning

confidence: 99%

“…Experimental and observational research has suggested the potential for adverse effects of statins, including type 2 diabetes (T2D), a side effect of particular interest because of its associated adverse health outcomes and impact on quality of life [9][10][11][12][13]. Accumulating evidence has suggested that statins increase the relative risk (RR) of T2D by 5%-55% [10][11][12][13][14][15], with potentially elevated statin-associated T2D risk in females [16], younger populations compared to older populations, and populations with lower LDL-C compared to populations with higher LDL-C [15]. Such findings merit further investigation in light of evolving statin recommendations that target growing proportions of populations for ASCVD primary prevention, for whom the net effects of statins remain incompletely quantified [17].…”

Section: Introductionmentioning

confidence: 99%

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Projections of incident atherosclerotic cardiovascular disease and incident type 2 diabetes across evolving statin treatment guidelines and recommendations: A modelling study

et al. 2020

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BackgroundExperimental and observational research has suggested the potential for increased type 2 diabetes (T2D) risk among populations taking statins for the primary prevention of atherosclerotic cardiovascular disease (ASCVD). However, few studies have directly compared statin-associated benefits and harms or examined heterogeneity by population subgroups or assumed treatment effect. Thus, we compared ASCVD risk reduction and T2D incidence increases across 3 statin treatment guidelines or recommendations among adults without a history of ASCVD or T2D who were eligible for statin treatment initiation. Methods and findingsSimulations were conducted using Markov models that integrated data from contemporary population-based studies of non-Hispanic African American and white adults aged 40-75 years with published meta-analyses. Statin treatment eligibility was determined by predicted 10-year ASCVD risk (5%, 7.5%, or 10%). We calculated the number needed to treat (NNT) to prevent one ASCVD event and the number needed to harm (NNH) to incur one incident case of T2D. The likelihood to be helped or harmed (LHH) was calculated as ratio of NNH to NNT. Heterogeneity in statin-associated benefit was examined by sex, age, and statin-associated T2D relative risk (RR) (range: 1.11-1.55).

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“…However, Possible Diabetes association with statins therapy has begun discussion in the medical community [5]. Meta-analyses of randomized clinical trials of lipid-lowering with statins suggest that individuals assigned statins were at slightly increased, approximately 9%-12%, in risk of type 2 diabetes mellitus (T2DM) compared with those assigned placebo or standard care [6,7,8]. Since the incidence of this effect cannot be ignored, especially for certain populations, this review aims to examine the relationship between statin treatment and the presence of diabetes.…”

Section: Introductionmentioning

confidence: 99%

Diabetes Caused by Statin Use: A Review

Zulfiana

Medina

Suharjono³

2020

J. Islamic Pharm.

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<p>Statins are generally recognised as being safe and well tolerated cholesterol-lowering drug and have been successfully used for prevention of primary and secondary cardiovascular disease. However, Some researchers have reported diabetes development in patients taking statins. A number of meta-analyses conducted in recent years have proved that the association is real even though its causality have not been fully elucidated. Various pathophysiological mechanisms that could explain the increased risk of diabetes in patients treated with statin have been described. These are mainly responsible for impairment of β -cell insulin secretion and alteration of intercellular signaling through depletion of important downstream products. This review aims to examine the relationship between statin treatment and the presence of diabetes. Previous clinical reviews of the evidence and pathophysiological mechanisms involved may also be explained. Furthermore, many studies have concluded that Pitavastatin and pravastatinom do not affect glycemic control and may be a beneficial treatment option in patients with, or at risk for, type 2 diabetes.</p>

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Evidence of heterogeneity in statin-associated type 2 diabetes mellitus risk: A meta-analysis of randomized controlled trials and observational studies

Cited by 12 publications

References 49 publications

Association of statin use in older people primary prevention group with risk of cardiovascular events and mortality: a systematic review and meta-analysis of observational studies

Association of statin use in older people primary prevention group with risk of cardiovascular events and mortality: a systematic review and meta-analysis of observational studies

Projections of incident atherosclerotic cardiovascular disease and incident type 2 diabetes across evolving statin treatment guidelines and recommendations: A modelling study

Diabetes Caused by Statin Use: A Review

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