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Statin-Induced Diabetes In Women

Risk of type 2 diabetes heightened in elderly women with increase in statin dose.

Statins are a well-known class of cholesterol-reducing medication that is highly prescribed to target the reduction of low-density lipoprotein cholesterol. Studies have shown its benefits in reducing cardiovascular events and mortality in secondary prevention as well. Although, its effects are similar in men and women, it has not been well studied in elderly females. Previous meta-analyses studies have linked statin use with onset of diabetes, but a recent study showed an increase in risk of type 2 diabetes associated with statins via 3-hydroxy-3methylglutarl-CoA reductase inhibition.

In a recent analysis of a population-based longitudinal cohort study with data linkage to the national death index and to national databases of non-hospital episodes of medical care and prescription medications dispensing. Participants included 8,372 Australian women born between 1921 and 1926 (between 76 to 82 years old), alive at 1 January 2003, free of diabetes, and eligible for data linkage. Statin exposure was determined based on prescriptions dispensed between 1 July 2002 and 31 August 2013. The primary outcome was the new-onset diabetes, which was based on a new prescription for insulin, insulin analogues, or other glucose-lowering agents. The study objective was to evaluate and estimate the risk of new-onset diabetes associated with statin exposure in a cohort of elderly Australian women.

The study focused on the older cohort of women. The participants could have taken different statins at different doses over the 10-year follow-up interval, but the greatest proportion of subjects received atorvastatin followed by simvastatin. Also, there was a change in the statin dose as it tended to be toward a higher dose over time. The mean interval for which women took a statin was 6.5 years. The study showed ‘Dose effect’ where the increase in statin dosage heightened the risk of type 2 diabetes. Since the majority of the women progressed to higher doses of statins during the study, it is imperative for the general practitioners and elderly female patients to be aware of the risks. Moreover, response to the ‘dose effect’ suggested avoiding higher doses of statins in elderly women unless clinically deemed necessary and to monitor their blood glucose regularly to detect and manage diabetes.

The study found that over the 10 years of monitoring, there was an almost 50% increase in type 2 diabetes risk in women in their late seventies and eighties who took higher doses of statins and 5% of them were diagnosed with new-onset diabetes. Statin therapy increases the risk of new-onset diabetes in elderly women by 33% when taken in lower doses, and the risk increases with higher doses. The risk of new-onset diabetes went from a low 17% with the lowest doses of a statin to a high 51% with taking the highest doses. Multivariable Cox regression showed statin exposure was associated with a higher risk of treatment for new-onset diabetes (HR 1.33; 95% CI 1.04–1.70; p = 0.024). The risk translates into a number needed to harm (NNH) 131 patients (95% CI 62–1079) for every 5 years of treatment with statins. Risk increased with increasing dose of statin from the hazard ratio of 1.17 (95% CI 0.84–1.65) for the lowest dose to 1.51 (95% CI 1.14–1.99) for the highest dose.

Although the benefits of statins outweigh the risk of diabetes, the study suggested that overall, it depends on the indication for statin use in the first place. Considering the dose response for statins on new onset of diabetes, elderly women should not be exposed to higher doses of statins. The study also indicated that around one-third of users had not filled their statin prescription in the last 6 months prior to death or end of follow-up. Thus, in some cases, it may even be better to stop statins altogether in this patient population. However, those who had stopped statins were not classified in the study and the effect of stopping statins on temporal pattern of risk of adverse events remains unclear.

In a nutshell, elderly women currently taking statins should be carefully and regularly monitored for increased blood glucose to ensure early detection and appropriate management of this potential adverse effect, including consideration of de-prescribing. Lastly, ongoing risk assessment is of utmost importance to ensure optimal health outcomes and quality of life in older women.

Practice Pearls:

  • An increased risk of new-onset diabetes is associated with statin exposure.
  • Elderly women should not be exposed to higher doses of statins.
  • The study demonstrated the ‘Dose effect’ of statins, where increase in statin dose increases the risk of type 2 diabetes.

Reference:

  1. Chogtu B, Magazine R, and Bairy KL. Statin use and risk of diabetes mellitus. World J Diabetes. 2015 Mar 15; 6(2): 352-357.
  2. Jones M, Tett S, Peeters GMEE, Mishra GD, and Dobson A. New-onset diabetes after statin exposure in elderly women: The Australian Longitudinal Study on Women’s Health. Drugs Aging. 2017; 34(3): 203-209.
  3.  Woodfield J. Elderly women taking statins have increased type 2 diabetes risk, research suggests. Diabetes News. 2017, 16 March.

Tenzing Dolkar, BSc., PharmD Candidate 2017, Lake Erie College of Osteopathic Medicine, School of Pharmacy