Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis.

By D. Preiss, S. Seshasai, P. Welsh, S. Murphy, J. Ho, D. Waters, D. Demicco, P. Barter, C. Cannon, M. Sabatine and 8 more. Journal of the American Medical Association (JAMA), 2011

1,214 citations recorded by the source corpus.

CONTEXT A recent meta-analysis demonstrated that statin therapy is associated with excess risk of developing diabetes mellitus. OBJECTIVE To investigate whether intensive-dose statin therapy is associated with increased risk of new-onset diabetes compared with moderate-dose statin therapy. DATA SOURCES We identified relevant trials in a literature search of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (January 1, 1996, through March 31, 2011). Unpublished data were obtained from investigators. STUDY SELECTION We included randomized controlled end-point trials that compared intensive-dose statin therapy with moderate-dose statin therapy and included more than 1000 participants who were followed up for more than 1 year. DATA EXTRACTION Tabular data provided for each trial described baseline characteristics and numbers of participants developing diabetes and experiencing major cardiovascular events (cardiovascular death, nonfatal myocardial infarction or stroke, coronary revascularization). We calculated trial-specific odds ratios (ORs) for new-onset diabetes and major cardiovascular events and combined these using random-effects model meta-analysis. Between-study heterogeneity was assessed using the I(2) statistic. RESULTS In 5 statin trials with 32,752 participants without diabetes at baseline, 2749 developed diabetes (1449 assigned intensive-dose therapy, 1300 assigned moderate-dose therapy, representing 2.0 additional cases in the intensive-dose group per 1000 patient-years) and 6684 experienced cardiovascular events (3134 and 3550, respectively, representing 6.5 fewer cases in the intensive-dose group per 1000 patient-years) over a weighted mean (SD) follow-up of 4.9 (1.9) years. Odds ratios were 1.12 (95% confidence interval [CI], 1.04-1.22; I(2) = 0%) for new-onset diabetes and 0.84 (95% CI, 0.75-0.94; I(2) = 74%) for cardiovascular events for participants receiving intensive therapy compared with moderate-dose therapy. As compared with moderate-dose statin therapy, the number needed to harm per year for intensive-dose statin therapy was 498 for new-onset diabetes while the number needed to treat per year for intensive-dose statin therapy was 155 for cardiovascular events. CONCLUSION In a pooled analysis of data from 5 statin trials, intensive-dose statin therapy was associated with an increased risk of new-onset diabetes compared with moderate-dose statin therapy.

Subfields: Cardiology and Cardiovascular Medicine, Endocrinology, Diabetes and Metabolism, Surgery

View Paper: https://www.semanticscholar.org/paper/27d04f5f6f027c3c719a0899dbcb3de462122f22

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cardiology and Cardiovascular Medicine

1. George Davey Smith
2. J. Forbes
3. K. F. Schulz
4. M. Cooper
5. P. Ridker
6. R. Legro
7. I. Graham
8. L. Melvin

In Endocrinology, Diabetes and Metabolism

1. J. Armitage
2. J. Forbes
3. George Davey Smith
4. M. Cooper
5. D. Ehrmann
6. P. Ridker
7. I. Graham
8. Massimo F. Piepoli

In Surgery

1. J. Armitage
2. J. Forbes
3. J. Liao
4. George Davey Smith
5. M. Cooper
6. R. Collins
7. M. Law
8. Sekar Kathiresan

Citations in the corpus

• Epidemiology of diabetic retinopathy, diabetic macular edema and related vision loss (2015, background): “Moreover, a meta-analysis found that there was a dose-dependent relationship of statin use with increasing risk of diabetes [104].”
• Atherosclerotic Cardiovascular Disease and Heart Failure in Type 2 Diabetes – Mechanisms, Management, and Clinical Considerations (2016, neutral): “The risk of developing diabetes mellitus appears to be related to statin potency(200) and dose.(189) Cellular mechanisms underlying the increased incidence of diabetes mellitus remain incompletely understood.”
• Mechanisms of diabetic complications. (2013, background): “This issue remains an ongoing controversy (473, 518), but it appears that effects of statin therapy on the development of diabetes, either positive or negative, are modest at best.”
• Developing medicines that mimic the natural successes of the human genome: lessons from NPC1L1, HMGCR, PCSK9, APOC3, and CETP. (2015, background): “What might be the net effect on CHD of an intervention that lowers LDL-C while simultaneously increasing the risk of type 2 diabetes? From a metaanalysis of statin trials in the secondary prevention setting, it is clear that CHD risk is reduced with statin treatment (20).”
• Interpretation of the evidence for the efficacy and safety of statin therapy. (2016, background): “In subsequent meta-analyses of the available results from the randomized trials, standard statin dose regimens were associated with a proportional increase of about 10% in reported diabetes, and more intensive statin regimens (as used in JUPITER) with about a 10% further increase.(48,225) This exces”
• Pleiotropic Effects of Statins on the Cardiovascular System (2017, background): “However, statins, especially the high-intensity statins, increase the risk of diabetes mellitus.(125) Thus, the ability of the PPAR-γ agonists, thiazolidinediones, to lower blood sugar is in contrast to the effects of statins on PPAR-γ and”