What percentage of patients on statins (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors) develop pre-diabetes (impaired glucose regulation)?

Statin-Associated Diabetes Risk: Quantitative Evidence

Approximately 1-5% of patients on statins develop new-onset diabetes over 4-5 years of treatment, with the risk varying substantially by statin intensity and baseline diabetes risk factors. 1

Risk by Statin Intensity

Moderate-Intensity Statins

• Annual incidence: 0.1-0.3% per year 1, 2
• Over 4 years of treatment, approximately 1.2-1.5% develop diabetes compared to 1.2% on placebo 1
• This translates to one additional case of diabetes per 255 patients treated for 4 years 1
• The absolute annual excess is approximately 0.1 excess cases per 100 patients per year 1

High-Intensity Statins

• Annual incidence: 1.27-1.36% per year excess risk 1
• Approximately 4.8% develop diabetes over follow-up compared to 3.5% on placebo 1
• This represents a 36% relative increase in new-onset diabetes (RR 1.36,95% CI 1.25-1.48) 1
• The absolute annual excess is approximately 0.3 excess cases per 100 patients per year 1
• 12% higher risk compared to moderate-dose therapy 3

Pre-Diabetes Development

While the question specifically asks about pre-diabetes, the evidence predominantly addresses progression to frank diabetes rather than pre-diabetes. However:

• Statins cause modest increases in glucose and HbA1c levels 1
• Mean glucose increase: 0.04-0.12 mmol/L for moderate-intensity and 0.22 mmol/L for high-intensity statins 1
• Mean HbA1c increase: 0.06-0.09% for moderate-intensity and 0.08% for high-intensity statins 1
• Among patients with existing diabetes, statins cause a 10% relative increase in worsening glycemia with moderate-intensity and 24% increase with high-intensity therapy 1

Risk Concentration in High-Risk Populations

Approximately 62-67% of excess diabetes cases occur in patients in the highest quartile of baseline glycemia, regardless of statin intensity 1. This means:

• Patients with pre-existing diabetes risk factors (metabolic syndrome, HbA1c ≥6%, fasting glucose ≥100 mg/dl, BMI ≥30 kg/m²) have substantially higher absolute risk 1
• The relative risk remains consistent across baseline glycemia quartiles, but absolute risk varies dramatically 1
• Statins appear to accelerate diabetes diagnosis by approximately 5 weeks in predisposed individuals rather than causing de novo diabetes 1

Clinical Context: Benefit-Risk Balance

The cardiovascular benefits overwhelmingly outweigh diabetes risk:

• 5.4 cardiovascular events prevented for every one case of diabetes induced over 4 years 1
• Alternative estimates suggest 5-9 ASCVD events prevented per case of diabetes 1
• For every 100-150 people treated with statins, one cardiovascular event is prevented, while 500 people must be treated to cause one new case of diabetes 4
• The absolute risk reduction for major coronary events (0.42% annually) far exceeds the annual diabetes risk (0.1% annually) 2

Practical Management Implications

• Do not withhold statins due to diabetes risk in patients with cardiovascular indications 4
• For patients at high diabetes risk requiring statins, implement regular glucose monitoring 4
• Emphasize lifestyle interventions (weight loss, exercise) to mitigate diabetes risk 1, 4
• The development of diabetes does not reduce expected cardiovascular benefits and reinforces the need for continued statin therapy 1
• Consider that pravastatin and pitavastatin may have neutral effects on glycemic parameters, though this requires further validation 5

Important Caveats

The substantially higher diabetes rates in high-intensity statin trials (3.5% annual placebo rate vs 1.2% in moderate-intensity trials) 1 reflect more intensive biochemical screening (72% had HbA1c measured, 49% had serial glucose measurements) rather than true differences in baseline populations 1. This detection bias means published rates may overestimate clinically apparent diabetes in routine practice.