A new systematic review lends support to the idea that statins, which are life-saving cholesterol-lowering drugs, are associated with an increased risk of insulin resistance and type 2 diabetes [1].
Statins’ dark side
Statins, drugs that improve the lipid profile by reducing harmful LDL cholesterol, are considered one of the biggest successes in medicine in recent decades. Statins have probably saved millions of lives by reducing the cardiovascular risks associated with abnormally high levels of cholesterol in the blood (hypercholesterolemia). However, there is a growing concern that statins may also exacerbate insulin resistance, a hallmark of metabolic dysfunction and type 2 diabetes [2]. A newly published meta-analysis consolidates data from several previous studies to shed more light on this question.
A significant correlation
After assessing the quality of studies, the authors selected 11 of them for their review. Their selections included cohort studies, randomized controlled trials, and two previous meta-analyses.
Four studies linked statins to increased fasting glucose, glycated hemoglobin (HbA1c), and fasting insulin, all of which are established biomarkers of insulin resistance. A fifth study, which was the smallest study with only 21 participants, showed mixed results on these metrics.
The relationship between statin use and insulin resistance was shown to be dose-dependent in two of the studies. Larger doses of statins were linked to greater insulin resistance.
Five studies also delved into the relationship between different types of statins and the risk of incidence of type 2 diabetes. According to four of those studies, the risk was higher with high-potency statins. The fifth study showed that this increase in risk was independent of the type of statins used.
The connection between the length of statin use and the risk of developing type 2 diabetes was explored in two studies. Those studies’ findings indicate that the risk of diabetes is indeed influenced by the duration of statin use, with people who use statins for medium (31-365 days) or long-term periods (over 365 days) having a significantly higher chance of developing diabetes compared to those who use statins for shorter durations (under 31 days).
Mechanisms still unknown
The findings of this study mostly confirm already well-established suspicions about statins and insulin resistance, which caused the FDA to update the labels for statins with a cautionary note about an increased risk of diabetes. However, the exact mechanisms behind statins’ influence on insulin sensitivity and glucose metabolism are not fully understood. Proposed theories include a direct impact on pancreatic beta cells, which produce insulin [3], along with changes to lipid metabolism. Research is ongoing.
It is important to note, as the study’s authors do, that for most patients, the benefits of statins outweigh the increase in metabolic risk. However, like in many other cases, reaching for a pill might not be the best first strategy. For many people, managing cholesterol levels and decreasing cardiovascular risk would be more safely conducted through diet and exercise [4].
The authors also suggest that healthcare professionals might want to personalize their approach to statin prescription, such as by prescribing weaker statins, such as pravastatin and rosuvastatin, to people with lower cardiovascular risk.
Despite its unequivocal findings, this meta-analysis has its limitations, such as the small number of studies included. Due to statins’ extreme popularity, it is important to further investigate their link to insulin resistance and diabetes.
In conclusion, the present systematic review provides compelling evidence that statins are significantly associated with a decrease in insulin sensitivity, regardless of the type of statin used. These findings have important clinical implications for healthcare providers in managing patients with high cholesterol. However, a targeted approach may optimize treatment outcomes by selecting statins with a lower risk of causing insulin intolerance in patients at a higher risk of developing diabetes. This approach can help healthcare providers personalize treatment plans to meet the individual needs of their patients and achieve better health outcomes.
Literature
[1] Dabhi, K. N., Gohil, N. V., Tanveer, N., Hussein, S., Pingili, S., Makkena, V. K., … & Nath, T. S. (2023). Assessing the Link Between Statins and Insulin Intolerance: A Systematic Review. Cureus, 15(7).
[2] Thakker, D., Nair, S., Pagada, A., Jamdade, V., & Malik, A. (2016). Statin use and the risk of developing diabetes: a network meta-analysis. Pharmacoepidemiology and drug safety, 25(10), 1131-1149.
[3] Galicia-Garcia, U., Jebari, S., Larrea-Sebal, A., Uribe, K. B., Siddiqi, H., Ostolaza, H., … & Martín, C. (2020). Statin treatment-induced development of type 2 diabetes: from clinical evidence to mechanistic insights. International Journal of Molecular Sciences, 21(13), 4725.
[4] Mirabelli, M., Chiefari, E., Arcidiacono, B., Corigliano, D. M., Brunetti, F. S., Maggisano, V., … & Brunetti, A. (2020). Mediterranean diet nutrients to turn the tide against insulin resistance and related diseases. Nutrients, 12(4), 1066.
