Statins and Diabetes

Cholesterol is vital to many body processes, including digestion of food and hormone production.  It comes from two main sources; the food we eat and from new production in our liver.  Much of the dietary cholesterol is broken down and excreted without being absorbed, but it influences the production of cholesterol in the body. The two types of cholesterol that exist are high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol. HDL, often referred to as “good” cholesterol, helps remove excess cholesterol from your body.  

Statins are important medications used primarily to treat dyslipidemia and to reduce the levels of the low-density lipoprotein (LDL) form of cholesterol (“bad” cholesterol) in the bloodstream, and thus reduce the impact of cholesterol on the risk of cardiovascular diseases like heart attack or stroke.  They are frequently prescribed to those with diabetes, because diabetes is considered an equivalent risk factor for heart disease, but could they actually increase the risk of other diseases?⁸

What are Statins and what do they do?

“Statins” is the common name for a group of drugs called HMG-CoA Reductase Inhibitors. HMG-CoA Reductase is an enzyme that moderates the biosynthesis of cholesterol in your liver, so inhibiting this enzyme reduces cholesterol levels and prevents high blood cholesterol (clinically known as hypercholesterolaemia). Statins also help the body to reabsorb cholesterol from the blood, which lowers the risk of arteries becoming blocked and forces the body to seek other sources to meet its needs. This extra cholesterol is obtained by reabsorbing the LDL (“bad”) cholesterol that has formed plaques on the walls of the arteries. In addition to the cholesterol-lowering effects, statins have pleiotropic effects that might reduce the risk of cardiovascular disease and diabetes.¹

Taking Statins

According to the NHS, statins come in the form of tablets that are taken once a day. Usually, statins must be taken for life, as cholesterol levels will increase again after a few weeks of not taking them.  If a dose is missed for any reason, it should not be compensated for by taking extra the next day.

Some foods may interfere with taking statins. For example, grapefruit or grapefruit juice should be avoided when taking simvastatin (Zocor) or to a lesser extent atorvastatin (Lipitor), since it can increase the levels of drug in the blood and lead to an increased risk of side effects.

Types of Statin

In the UK, there are five types of statin available on prescription:

• atorvastatin (Lipitor)
• fluvastatin (Lescol)
• pravastatin (Lipostat, Pravachol)
• rosuvastatin (Crestor, Ezallor)
• simvastatin (Zocor, Flolipid)

Other types include lovastatin (Prevacor, Altoprev) and pitavastatin (Livalo) but these are not currently available on the NHS. The statins have different intensities of therapeutic activity against LDL cholesterol and the one prescribed depends on how high your blood cholesterol level is. For example, atorvastatin and rosuvastatin are high intensity statins, while fluvastatin and pravastatin are lower intensity.

Side Effects of Statins

Like most medications, statins have side effects, and the Mayo Clinic explains how to weigh the benefits of taking them (lower cholesterol, lower heart disease risk) against the risks. Many side effects are related to dose and the intensity of statin therapy. Common side effects of statins include:

• headache
• dizziness
• nausea
• feeling unusually tired or physically weak
• digestive system problems, such as constipation, diarrhoea, indigestion, or flatulence
• muscle pain
• sleep problems
• low blood platelet count

Less common side effects of statins include:

• vomiting
• memory problems
• mental fuzziness/confusion
• alopecia (hair loss)
• pins and needles
• hepatitis (inflammation of the liver), which can cause flu-like symptoms, jaundice and upper abdominal pain
• pancreatitis (inflammation of the pancreas), which can cause stomach pain
• raised blood sugar and type-2 diabetes
• skin problems, such as acne or an itchy red rash
• sexual problems, such as loss of libido or erectile dysfunction
• Increased blood sugar

Rare side effects of statins include:

• muscle weakness (myopathy)
• muscle inflammation and damage (rhabdomyolysis)
• loss of sensation or tingling in the nerve endings of the hands and feet (peripheral neuropathy)
• tendon problems (tendons are tough cords of tissue that connect muscles to bones)

(Sources: NHS, Mayo Clinic)

Muscle pain is a very common side effect of statins, but the Mayo clinic describe what they call a “nocebo” effect, in which people get muscle pain because they’re expecting to get it, after having read that statins cause muscle pain. Studies have shown that 30% of people stop taking the pill due to muscle aches even if the pills are actually placebos and not statins.  

More severe than simple muscle pain is a condition called rhabdomyolysis, a rare (and reversible, but potentially life-threatening) side effect of severe muscle injury, toxins, and some statins at high doses, especially in combination with drugs such as cyclosporine and gemfibrozil. Rhabdomyolysis can cause severe widespread muscle pain, liver damage, kidney failure, and even death in extreme cases. It should be emphasised that the risk is extremely low and calculated in a few cases per million people taking statins.

Factors affecting the risk of developing statin side effects

Not every person who takes statins will have side effects, and not every person will experience them to the same degree, but some factors and characteristics may increase the risk, such as:

• Being female
• Having a smaller body frame
• Being aged 80 or older
• Having kidney or liver disease
• Drinking too much alcohol
• Having certain conditions such as hypothyroidism or neuromuscular disorders including amyotrophic lateral sclerosis (ALS, or Lou Gehrig’s Disease) 
• Taking multiple medications to lower your cholesterol, or some other drugs

Many drug types interact with statins and may increase the risk of side effects, including:

• Amiodarone (Cordarone, Pacerone), a medication for irregular heart rhythms
• Warfarin, an anticoagulant
• Gemfibrozil (Lopid), another variety of cholesterol drug
• HIV treatments called protease inhibitors such as saquinavir (Invirase) and ritonavir (Norvir)
• Some antibiotic and antifungal medications, such as clarithromycin and itraconazole (Onmel, Sporanox)
• Some immunosuppressant medications, such as cyclosporine (Gengraf, Neoral, Sandimmune)

Relieving the side effects of statins

If side effects are severely impacting your quality of life, a doctor should be consulted. There are several ways to alleviate the side effects:

• Take a brief break from statin therapy. This can help you see whether your aches and pains are due to statins rather than something else, like ageing or vigorous exertion.
• Switch to another statin, possibly one with a lower intensity.
• Take it easy when exercising. Unaccustomed vigorous exercise might increase the risk of muscle injury, which could be mistaken for statin side effects. 

• Consider other cholesterol-lowering medications. Although statins are the most effective oral medications for lowering your cholesterol, many other types of drugs and supplements also are available.
• Coenzyme Q10 supplements may help prevent statin side effects in some people, though more studies are needed to determine the true benefits of taking it. A doctor should be consulted to ensure that taking the supplement won't interact with any of your other medications.

Alternative ways to lower cardiovascular risk

As alternatives to drug therapy for high cholesterol, there are many lifestyle changes which can diminish the risk of cardiovascular diseases. Stopping smoking, giving up alcohol, and eating healthily can all help. Some foods contain high levels of plant sterols which have been shown to lower cholesterol by reducing absorption in the gut.

FAQ’s

• Do statins increase risk for diabetes?
  • The risk of incident type 2 diabetes has been reported, by some studies, to be increased by statins, particularly high intensity ones.^{1, 2, 4}  The risk is relatively small (less than 1%), and depends on the dose of statin and other underlying diabetes risk factors (such as a family history of diabetes, BMI, high blood sugar, prediabetes).^{6, 7}  One study (West of Scotland Coronary Prevention Study or WOSCOPS) with pravastatin reported a protective effect of statin use on diabetes incidence, whereas the JUPITER trial with rosuvastatin reported an increased risk. The JUPITER results suggest that statins simply accelerate the onset of diabetes in those who would develop it anyway. In fact, three large meta-analyses of statin safety data indicated that the benefits of statins vastly outweigh the risks and that some statins like pravastatin actually reduced diabetes risk.^{3, 5, 6}
• Which statins carry the highest and lowest risk of diabetes?
  • MD/Alert reported that some statins raise blood sugar and HbA1c, and thus increase the risk of type 2 diabetes. Higher-intensity statins, such as atorvastatin, rosuvastatin, and simvastatin increased the risk of newly diagnosed diabetes compared to treatment with fluvastatin or lovastatin over a 14-year period. Pravastatin appeared to have the lowest risk and rosuvastatin had the highest, according to a meta-analysis reviewed by the authors.
• Do statins make you age faster?
  • Some of the uncommon side effects of statins like fatigue and memory loss could be seen as signs of ageing. One study has found that statins are associated with longer telomeres (the structures at the ends of the chromosomes that shorten with age), and thus statins could actually slow ageing. It’s possible that statins improve some biological functions associated with ageing and worsen others.
• Do statins clear the arteries of plaque?
  • Yes. By reducing total cholesterol in the blood, statins encourage the reabsorption of LDL cholesterol plaques in the arteries.
• Which statin is used for diabetes?
  • Most statins can be prescribed for diabetes patients, but they’re not a diabetes treatment themselves. Factors such as the perceived risks such as the propensity to raise blood sugar levels, will be considered by the doctor.
• Should people with type 2 diabetes take statins?
  • Statins greatly reduce the risk of heart attacks and strokes in people with diabetes, so the importance of the mild increase in blood sugar seen in some people on statins is unclear. The benefit of taking statins likely outweighs the small risk to have the blood sugar level go up, but the risks and benefits of prescribing statins are carefully weighed up in each individual case by a physician.
• Which statins do not raise blood sugar?
  • The low-intensity statins, pravastatin, fluvastatin, and lovastatin, have a minimal effect on blood sugar and HbA1c.
• Do statins make Type 2 diabetes worse?
  • The effect of statins on diabetes severity is controversial. By raising blood sugar and HbA1c, some statins may appear to weaken diabetes control, but this can be compensated for in other ways, particularly diet, and increased doses of insulin if it’s being used.