Do statins increase the risk for the development of diabetes?
Bibliographic record
Abstract
EVIDENCE-BASED ANSWER Statin therapy increases the risk of new-onset diabetes mellitus (SOR: A, 2 meta-analysis of randomized controlled trials and observational studies). High-intensity statins carry a higher risk of development of new-onset diabetes compared with low-intensity statins (SOR: B, meta-analysis of observational studies), with higher risk seen in atorvastatin and rosuvastatin (SOR: B, large retrospective cohort study).This clinical question was developed as an HDA through a standardized, systemic methodology (HDA Methods, Supplemental Digital Content). A 2019 meta-analysis of 33 randomized controlled trials (RCTs; N=163,688) examined new-onset diabetes (NODM).1 Patients had a mean age of 59.9 years old, with 18% to 100% male across the trials. Patients were included if they had hypercholesterolemia, atherosclerotic cardiovascular disease (ASCVD) risk factors, previous myocardial infarction (MI) or acute coronary syndrome (ACS), coronary heart disease (CHD), congestive heart failure, or valvular heart disease. The intervention group received statin therapy, whereas the control group included usual care or placebo. Follow-up ranged from 104 to 349 weeks. The primary outcome was NODM that was defined as multiple criteria, including adverse events (unspecified), one or two fasting blood glucose measurements >126 mg/dL, positive oral glucose tolerance test, WHO 1999 criteria, and starting a diabetes medication. Statin “intensity” indicated potency of the statin used. Compared with patients who did not take a statin, patients who took any statin were significantly more likely to develop NODM (21 RCTs, N=124,755; risk ratio [RR] 1.09; 95% CI, 1.03–1.16). High-intense statins were significantly associated with a higher risk of NODM compared with low-intensity statin therapy (21 RCTs, N=124,755; RR 1.11; 95% CI, 1.03–1.19; I2=0%). This study was limited by different definitions of NODM across the trials. A 2017 meta-analysis of 20 observational studies (N=4,066,854) evaluated the development of diabetes in patients taking statins versus not taking statins.2 Patients were adults, with a mean age of 56.9 years old. No other demographic information was provided. Follow-up duration across the studies ranged from 2 to 20 years, with a mean duration of 7.2 years. Studies were included if they had at least 1,000 adult patients followed for at least one year. The primary outcome was NODM that was defined as receiving a diagnosis, taking diabetes medications, self-report, biochemical markers, or a combination of these. Compared with patients who did not take a statin, patients who took any statin were significantly more likely to develop NODM (19 studies, N=4,055,139; RR 1.44; 95% CI, 1.31–1.58). In addition, compared with patients who took low-intensity statins, patients who took the high-intensity statins were more likely to develop NODM: simvastatin (8 studies, N=77,372; RR 1.38; 95% CI, 1.19–1.61), pravastatin (8 studies, N=63,912; RR 1.39; 95% CI, 1.09–1.77), fluvastatin (6 studies, N=7,022; RR 1.39; 95% CI, 1.09–1.77), rosuvastatin (6 studies, N=38,155; RR 1.61; 95% CI, 1.31–1.98), and atorvastatin (7 studies, N=51,121; RR 1.49; 95% CI, 1.31–1.70). This study was limited by broad inclusion criteria and definitions of NODM. A 2022 multicenter, retrospective cohort study (n=14,605,368) compared risk of NODM in new patients of pitavastatin versus atorvastatin and rosuvastatin.3 Patients were adults (age >18 years old) from 10 hospitals in Korea and used statins for >180 days. Patients were excluded if they had prior exposure to the studied statins or other statins (including simvastatin, pravastatin, lovastatin, or fluvastatin), or an exposure to any oral hypoglycemic agent, glucagon-like peptide-1 (GLP-1) receptor agonist, insulin, or had a serum HbA1c >5.7%. The primary outcome was incidence of NODM 180 days after starting statin therapy. NODM was defined as diagnosis of diabetes using ICD-10, prescription of hypoglycemic agent, GLP-1 receptor agonist, or insulin, and serum HbA1c level >6.5%. Pitavastatin was associated with a significantly lower risk of NODM compared with atorvastatin (hazard ratio [HR] 0.69; 95% CI, 0.54–0.88) or rosuvastatin (HR 0.74; 95% CI, 0.55–0.99). No significant difference in the risk of NODM was noted between atorvastatin and rosuvastatin.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.020 | 0.089 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.007 | 0.006 |
| Bibliometrics | 0.003 | 0.003 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.004 | 0.003 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.007 | 0.004 |
| Insufficient payload (model declined to judge) | 0.013 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".