Do Statins Cause Diabetes?

Life would be so much easier if there were binary, yes and no answers to every question that was important to us.

But there isn’t.

And even for so many of the questions you ‘think’ that have clear-cut answers, there actually aren’t.

You just think there are.

Let me explain. 

Does speeding cause car crashes?

Most of you would agree that the answer here is a clear ‘yes’.

But it’s not.

The real answer is driving at higher speeds ‘increases’ the likelihood of a car crash.

You could drive around for the rest of your life, far in excess of the speed limit, most of the time and never have a car crash.

It’s possible.

But it’s just unlikely.

We could eliminate car crashes entirely by banning driving, but we can all agree that the net harm to society would likely be unacceptable.

It all comes down to: 

• What your priorities are

• What your objectives are

• Your risk tolerance

• Your ability to update that risk model

• Where you draw the line of ‘risk’ equating to ‘causation’.

The same is true when it comes to the question of statins ‘causing’ diabetes.

If you want a binary yes/no answer to this question, this article is not for you.

If you want the nuanced data on this topic to help you make an informed decision, then read on.

JUPITER

In 2008 a landmark paper was published showing that in people without cardiovascular disease and relatively normal LDL-cholesterol (<3.4 mmol/l or 130 mg/dl), the use of rosuvastatin 20mg significantly reduced the likelihood of major cardiovascular events1.

The reduced events included:

• 44% reduction in major heart events (Heart attacks, strokes, cardiovascular death etc.)

• 20% reduction in All-Cause Mortality - Death from any cause

 

The benefits were so significant that the trial was stopped early after 1.9 years.

This was in a ‘relatively' healthy group of people.

However…..

There was a statistically significant increase in the risk of diabetes in the rosuvastatin arm.

Out of 17,802 people in the trial, the occurrence of newly diagnosed diabetes looked like this:

Placebo - New Onset Diabetes - 216 cases

Rosuvastatin - New Onset Diabetes - 270 cases

Not just JUPITER

Meta-analysis of multiple statin trials has shown this to be a consistent finding with an average 11% increased risk of new-onset diabetes across these studies2.

This risk is higher when higher-intensity statin therapy is used.

As a consequence, the US FDA and the European drug authorities included package insert warnings on the increased risk of diabetes with statin therapy.

What to do?

As with every question of this kind, the devil really is in the detail.

Let’s dive in.

Was the risk of new-onset diabetes evenly distributed across ALL the people in the trial?

No.

80% of the people in the JUPITER trial who went on to develop diabetes already had evidence of impaired fasting glucose at the start of the trial3.

They did not have diabetes at the start of the trial, but they were WELL on their way.

And when you have impaired fasting glucose, you likely have had insulin resistance for MANY years prior.

In addition to elevated fasting glucose, there are many other risk factors for developing diabetes, including:

• Metabolic syndrome

• BMI > 30 (Obese category)

• Elevated HBA1c - Not in the diabetes category but above normal.

Having at least one of these risk factors at the outset of the trial increased the likelihood of developing diabetes by 10-fold.

What seems to be happening is that those who are already highly likely to develop diabetes are diagnosed earlier.

How much earlier does it pull forward the diagnosis?

About 5 weeks in total4.

So Yes.

Statin therapy does increase the likelihood of newly diagnosed diabetes.

But…

• In general, the risk is small

• It is almost exclusively related to those who have preexisting risk factors for diabetes

• Is 10 times less in those who do not have existing major risk factors for diabetes.

But what about events?

The real question is whether those who went on to diabetes had less of a benefit from statin therapy in terms of preventing heart attacks and strokes.

For every 100 - 200 people treated with a statin, about 1 will go on to have a diagnosis of diabetes5.

That risk is small.

The benefit in terms of reduction of cardiovascular events is 10-fold greater.

There is no comparison.

The benefits wildly outweigh the risks.

But why do statins increase the risk of diabetes?

Type 2 diabetes is the end stage of the insulin resistance continuum.

When insulin resistance progresses to a point whereby glucose levels cannot be kept in check, glucose levels rise, and diabetes is then diagnosed.

We know this is a process that takes years and is preceded by worsening insulin resistance for quite a long time.

Why statins accelerate the time to diagnosis of diabetes is likely explained by increases in insulin levels and potential worsening of insulin resistance6.

What To Do?

Achieving lifelong low APOB/LDL-C concentrations is associated with very low rates of cardiovascular disease.

Statin therapy is a very reliable method of achieving that goal.

If insulin resistance is an issue for you, the good news is that for most people, it can be entirely reversed with appropriate attention to exercise, both aerobic and resistance, in addition to proper nutrition strategies.

In my practice, I follow the blood glucose parameters of all my patients, and if I see someone trending in the wrong direction who is on statin therapy and doing all the lifestyle measures mentioned, I do re-evaluate their lipid-lowering options.

Because of the increased risk, I am also quicker to introduce non-statin-based cholesterol-lowering agents such as ezetimibe, bempedoic acid, PCSK9 inhibitors or inclisiran when available.

The main takeaway is that statin therapy does result in a small increased risk of newly diagnosed diabetes, but 80% of the time, it is in those who were likely to develop diabetes at some point anyway.

If it does come up as an issue in my clinical practice, I am quick to introduce other methods of APOB/LDL-C lowering approaches.

So please do not be scared by the shock tactics used by some of those online when they talk about this topic.

The answer is nuanced.

Your approach requires this.

But there is always a way to navigate the problem.