The answer may depend on your blood-sugar status, and which statin you take, at what dose 05/16/2019
Does taking a heart-protecting statin drug raise your risk of diabetes?
Statins seem to make sense for some people at risk for sudden cardiac death, heart attacks, and strokes.
And they’re often prescribed for diabetics, who are about twice as likely to die from heart-related causes, compared with non-diabetics.
Given the higher heart risks for diabetics, it's a sad irony that statin drugs can actually promote the increasingly common blood-sugar disorder.
The apparent links between statins and diabetes haven’t been entirely clear, but recent findings may help doctors and patients decide on the wisdom and specific details of a statin prescription.
How statins work — or don’t — and potential side effects
One in four Americans has levels of cholesterol — especially the riskier LDL and VLDL forms — that raise the risk for heart disease and its potentially crippling or fatal outcomes.
Importantly, as a team from the National Institutes of Health, Harvard Medical School, and other institutions reported in 2018, Omega-3 Levels Beat Cholesterol at Predicting Death Risk.
Nearly one out of three American men and women over age 40 now take one of the several approved statin drugs, such as atorvastatin (Lipitor) and simvastatin (Zocor).
Statins lower blood levels of LDL cholesterol and can help lower blood levels of triglycerides, another key risk risk factor — one that can also be reduced with seafood-source omega-3s. Statins can also raise blood levels of HDL cholesterol, which is generally heart-protective.
These drugs can help certain people avoid strokes and heart attacks. But a minority of people suffer adverse side effects, including digestive problems, muscle pain, mental confusion and, rarely, liver damage.
And because statins can raise blood sugar (glucose) levels, the Food and Drug Administration (FDA) requires a diabetes warning on statin drug labels.
Importantly, the value of statins for people without heart disease who nonetheless display major risk factors for heart disease — especially high levels of LDL cholesterol and forms considered more dangerous — is the subject of debate, even within the cardiology community.
For example, in 2012, the Wall Street Journal published a debate between two cardiologists, concerning the value of prescribing statins for “primary prevention” of heart disease, heart attacks, strokes, and sudden cardiac death among people without heart disease who have relatively high levels of LDL cholesterol.
Interestingly, the doctor who argued that statins shouldn’t be prescribed to people without heart disease — cardiologist Rita Larson, M.D. — noted the risk that statins can promote diabetes.
As Dr. Larson wrote in the Journal, “Using the most optimistic projections, for every 100 healthy people [with high cholesterol] who take statins for five years, one or two will avoid a heart attack. One will develop diabetes. But, on average, there is no evidence that the group taking statins will live any longer than those who don't.”.
In addition, as Dr. Larson noted, “Besides increasing the risk for developing diabetes, statins can cause memory loss, muscle weakness, stomach distress, and aches and pains. These aren't merely anecdotal results, as some critics assert; they're documented by recent studies.”
Dr. Larson also stressed that lifestyle measures rival the benefits of statins:: “If we were to spend a small fraction of the annual cost of statins on making fruits and vegetables and physical activity more accessible, the eﬀect on heart disease, as well as high blood pressure, diabetes, cancer and overall life span, would be far greater than any beneﬁt statins can produce.”
And diets rich in seafood and their omega-3 fatty acids (DHA and EPA) can rival or add to the benefits of statins. For example, see Omega-3s Seen Rivaling Statins at Reducing Risk of Death, Omega-3s Boost Statin Benefits, Omega-3s Add to Statin Drugs' Cardio Benefits, and Statin Drug Beaten by Alternative Cholesterol Treatment.
Statins may only help half of those taking them
The results of a recent study suggest that about half of all people taking statins don’t receive a very significant reduction in their risk of developing heart disease.
This British study involved 165,411 people who were free of cardiovascular disease but who — due to high cholesterol levels — had started taking statins between 1990 and 2016.
After being followed for more than six years, slightly more than half the participants displayed “suboptimal” responses, meaning that their LDL cholesterol levels dropped by less than 40% over the course of the study (Akyea RK et al. 2019).
And the slight majority of participants deemed sub-optimally responsive to statins were 25% more likely to die from cardiovascular disease, compared to the slightly smaller proportion of optimal statin-responders. (That finding was calculated after the authors accounted for known cardiovascular risk factors, including the participants’ initial cholesterol levels.)
The authors speculated, plausibly, that some people may be genetically predisposed to either resist or respond to the cholesterol-lowering and other (e.g., anti-inflammatory) seemingly beneficial effects of statins.
When it comes to statins, three things seem reasonably clear:
- Statins significantly reduce the risk of a major adverse cardiac event among people who’ve already suffered one such event (so-called “secondary prevention”).
- Statins do much less for people with high cholesterol who don’t have diagnosed heart disease. In fact, as Dr. Larson pointed out in the 2012 Wall Street Journal debate, the “absolute” reductions in risk for such people (versus the much less meaningful “relative” risk reductions) are just a few percentage points.
- Among people prescribed statins for primary prevention, only a tiny proportion will avoid an adverse cardiovascular event that might otherwise have occurred, making the ratio of benefit to cost very small.
Large study detailed the diabetes risk from statins
There’s ample evidence demonstrating a link between statins and higher risk for type 2 diabetes.
Recent studies have clarified the degree of risk, which statins are riskiest, and how people taking statins can reduce their consequent diabetes risk.
To gauge the risk of diabetes in statin users, researchers from the University of Milan conducted a meta-analysis of 43 studies, each involving more than 1,000 subjects who were followed for at least one year (Casula M et al. 2017).
The results suggest that statins raise the risk of developing diabetes by nine to 13 percent — a larger risk than previously suspected. The research team proposed that earlier studies may have underestimated the risk because of their short follow-up periods and smaller sizes.
They also found that not all statins are equal when it comes to the risk of type 2 diabetes. The statins known to reduce cholesterol levels the most also raised diabetes risk the most.
And they urged physicians to monitor patients taking statins — especially those with other risk factors for diabetes, such as being overweight and sedentary — or who are deemed prediabetic because they have higher than normal levels of blood sugar.
We recently covered an ongoing controversy about the diabetes-predictive value of a prediabetes diagnosis: see Is “Prediabetes” a Real Risk for the Real Thing?.
As it happens, a diagnosis of prediabetes may be equally or more valuable when it comes to deciding whether someone with cardiovascular risk factors should take a statin drug, and if so, which specific statin at what intervals and dose.
Dutch study affirms the statin-diabetes link; Ways to reduce that risk
Another study, from researchers at Holland’s Erasmus University, followed 9,535 volunteers aged 45 years or older — all free of diabetes at the outset — for 15 years.
It found that the participants who were taking statins tended to have above-normal levels of fasting insulin — the hormone that prompts uptake of blood sugar (glucose) into cells.
That finding matters because abnormally high fasting-levels of insulin indicates the development of insulin resistance — an early warning sign for diabetes risk — before someone’s blood sugar levels rise to the levels that prompt a diagnosis of full-blown diabetes.
Critically, the participants who took statins were 38% more likely to develop type 2 diabetes during the 15-year study, compared with the volunteers who didn’t take the cholesterol-lowering drugs (Stricker B et al. 2019).
Unsurprisingly, the link was strongest in those who were already at risk for type 2 diabetes (i.e., were prediabetic) because they were overweight or obese and had higher than normal blood sugar levels.
As study leader Bruno Stricker, PhD, said, “The findings suggest that in patients who initiate statin therapy, preventive strategies such as blood sugar control and weight loss may be warranted for minimizing the risk of diabetes.”
A separate study from Korea supports previous studies showing not all statins carry the same diabetes risk, with the stronger statins — those that lower cholesterol the most — tend to raise the risk for type 2 diabetes the most (Kim J et al. 2018).
What if you're at cholesterol-related risk for heart disease?
If your doctor urges you to take statins, it makes sense to first determine whether you have risk factors for diabetes.
Statins shouldn’t be a knee-jerk reaction to high cholesterol levels. As cardiologist Rita Larson, M.D., said in the 2012 Wall Street Journal debate, many people can substantially reduce their heart risks by eating a healthy diet, losing excess weight, and getting regular exercise.
While lifestyle changes don’t always reduce high cholesterol levels to a sufficient extent — largely for genetic reasons — they can reduce the risk for cardiovascular disease and its adverse outcomes.
If you do decide to take statins, it makes sense to ask your doctor to check your liver function and blood-sugar levels regularly and get any other tests he or she recommends.
Finally, if your blood sugar levels rise significantly after you start taking a statin, talk to your doctor about switching to another, weaker statin, taking statins every other day instead of daily, and/or lowering the dosage.
- Akyea RK, Kai J, Qureshi N, Iyen B, Weng SF. Sub-optimal cholesterol response to initiation of statins and future risk of cardiovascular disease. Heart. 2019 Apr 15. pii: heartjnl-2018-314253. doi: 10.1136/heartjnl-2018-314253. [Epub ahead of print]
- American Heart Association. Cholesterol Medications. Accessed at https://www.heart.org/en/health-topics/cholesterol/prevention-and-treatment-of-high-cholesterol-hyperlipidemia/cholesterol-medications
- Casula M, Mozzanica F, Scotti L, Tragni E, Pirillo A, Corrao G, Catapano AL. Statin use and risk of new-onset diabetes: A meta-analysis of observational studies. Nutr Metab Cardiovasc Dis. 2017 May;27(5):396-406. doi: 10.1016/j.numecd.2017.03.001. Epub 2017 Mar 10. Review. Accessed at https://www.nmcd-journal.com/article/S0939-4753(17)30043-1/fulltext
- Centers for Disease Control and Prevention (CDC). Cholesterol Lowering Medications. Accessed at https://www.cdc.gov/cholesterol/treating_cholesterol.htm
- Centers for Disease Control and Prevention (CDC). Diabetes Basics. Accessed at https://www.cdc.gov/diabetes/basics/index.html
- Chrysant S. New onset diabetes mellitus induced by statins: current evidence, Postgraduate Medicine, 2017. Accessed at https://www.tandfonline.com/doi/abs/10.1080/00325481.2017.1292107?journalCode=ipgm20
- Food & Drug Administration (FDA). Controlling Cholesterol with Statins. Accessed at https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm293330.htm
- Kaasenbrood L et al. Development and Validation of a Model to Predict Absolute Vascular Risk Reduction by Moderate-Intensity Statin Therapy in Individual Patients With Type 2 Diabetes Mellitus: The Anglo Scandinavian Cardiac Outcomes Trial, Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, and Collaborative Atorvastatin Diabetes Study. Circ Cardiovasc Qual Outcomes. 2016 May;9(3):213-21. doi: 10.1161/CIRCOUTCOMES.115.001980. Epub 2016 May 11.
- Kim J et al. Effect of statins on fasting glucose in non-diabetic individuals: nationwide population-based health examination in Korea, Cardiovascular Diabetology, 2018. Accessed at https://cardiab.biomedcentral.com/articles/10.1186/s12933-018-0799-4
- Mayo Clinic. Statin side effects: Weigh the benefits and risks. Accessed at https://www.mayoclinic.org/diseases-conditions/high-blood-cholesterol/in-depth/statin-side-effects/art-20046013
- Stam-Slob MC, Visseren FL, Wouter Jukema J, van der Graaf Y, Poulter NR, Gupta A, Sattar N, Macfarlane PW, Kearney PM, de Craen AJ, Trompet S. Personalized absolute benefit of statin treatment for primary or secondary prevention of vascular disease in individual elderly patients. Clin Res Cardiol. 2017 Jan;106(1):58-68. doi: 10.1007/s00392-016-1023-8. Epub 2016 Aug 23.
- Stricker B et al. Associations of statin use with glycaemic traits and incident type 2 diabetes. British Journal of Clinical Pharmacology, 2019. Accessed at https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bcp.13898