Our first inkling that statins and diabetes might be a problem came in 2003. That’s when a reader of our syndicated newspaper column reported a rapid rise in blood sugar after taking atorvastatin (Lipitor). Now, a study published in JAMA Internal Medicine (Oct. 4, 2021) reports that some people with diabetes can indeed experience significant difficulty managing their blood glucose levels when they are on a statin.
The Study on Statins and Diabetes:
Texas researchers combed the national VA Corporate Data Warehouse for medical records between October 1, 2002 and September 30, 2015. They found 83,022 patients who started statin therapy within the time frame of the study. They also located 83,022 controls (“active comparators”) who were not taking statins.
The investigators were asking an important question:
“What is the association of statin treatment initiation and diabetes progression in patients with diabetes?”
In other words, did statin therapy make diabetes management more difficult? Did patients need to take more diabetes medicine or begin insulin injections after starting statins?
There were a few other critical questions:
1) Did patients with diabetes have 5 or more measurements of blood glucose above 200mg/dL? A rough rule of thumb is that blood sugar levels should be under 130 before eating and no higher than 180 an hour or two after eating. Some experts aim for tighter control.
2) Did patients receive a new diagnosis of diabetes with ketoacidosis or uncontrolled diabetes during the treatment timeline?
3) Did patients need a number of different kinds of diabetes meds?
4) How much did blood glucose change during follow-up compared to baseline?
What Was the Effect of Combining Statins and Diabetes?
Here in their own words are the researchers’ findings:
“Statin users had significantly higher odds of diabetes progression compared with nonusers. There was significantly higher rate of each component of the diabetes progression outcome in statin users compared with nonusers including an increase in the number of glucose-lowering medication classes, new insulin starts, presence of persistent hyperglycemia [high blood glucose], and new diagnosis of ketoacidosis or uncontrolled diabetes.”
“Intensive cholesterol lowering was associated with highest odds of diabetes progression outcome among statin users in compared with nonusers.”
The Dose-Response Curve:
That last data point is important. As a pharmacologist, I always look at the dose-response curve. The most simplistic description goes something like this: a small dose elicits a small effect; a middle dose leads to a medium response and a high dose creates a big effect.
Imagine an experiment where 100 people take a baby aspirin. A relatively small number will experience stomach upset. Another 100 subjects are given two aspirin pills. Quite a few more will have an upset stomach. The last 100 volunteers will be given six aspirin pills. Many will complain of heartburn or stomach pain.
If we plotted dose against the number of people who complained of digestive distress, we would have a dose-response curve. That kind of graph gives us confidence that the drug is really causing the adverse reaction in question.
I would say that there is little doubt that statins are indeed making blood sugar control more challenging. The higher the dose, the greater the connection between statins and diabetes progression.
Here is how the researchers summarize their findings about statins and diabetes:
“This study of a national cohort of VA patients with diabetes found that statin use was associated with an escalation of diabetes treatment, including a higher risk of initiating insulin and the use of more glucose-lowering medication classes. This escalation of diabetes treatment was associated with worse diabetes control, including new persistent hyperglycemia and acute glycemic complications. Moreover, there was a dose-response association between intensity of lowering LDL cholesterol and risk of the study outcomes, with higher intensity of LDL cholesterol-lowering associated with higher odds of diabetes progression.”
The Guidelines Require Doctors to Prescribe Statins to Patients with Diabetes!
Here’s an interesting conundrum for you. The guidelines that doctors are supposed to follow demand that all patients with type 2 diabetes between 40 and 75 years of age must receive a prescription for statins. Doctors who do not follow the guidelines often get dinged.
Those guidelines exist even though we have known for years that statins lead to insulin resistance and higher blood sugar levels. Patients on statins often have higher hemoglobin A1c (HbA1c) levels.
So What If Statins and Diabetes Are Related?
Many cardiologists and diabetes experts have shrugged their shoulders about the statins and diabetes connection. Their position is that cardiovascular complications are a serious consequence of diabetes. Therefore, lowering LDL cholesterol is a primary goal and diabetes progression is not something to be very concerned about.
The authors of the new JAMA study offer a counter argument:
“The higher risk of diabetes progression associated with statin use may seem less consequential, at least in the short and intermediate term, than the cardiovascular benefits of statin use, especially when used for secondary prevention. However, diabetes progression has long-term effects on quality of life and treatment burden, which warrant consideration when discussing the overall risk-benefit profile, especially when used for primary prevention…A recent cohort study reported that patients with diabetes with 5 risk factors within a target control range (eg, LDL cholesterol <97 mg/dL) had little or no excess risk of CVD outcomes. Of note, 61.5% of patients in this cohort used statins, and HbA1C was a stronger predictor than LDL cholesterol of risk of death from any cause.”
I bet your eyes glazed over before you got to that last sentence. It’s a zinger, though. HbA1C is a measure of blood sugar control over several weeks. Doctors have come to rely upon this measure as a way of determining how well someone with diabetes is controlling their blood sugar. Here’s the last sentence again:
“Of note, 61.5% of patients in this cohort used statins, and HbA1C was a stronger predictor than LDL cholesterol of risk of death from any cause.”
It contradicts the idea that LDL cholesterol levels are more important than blood sugar levels. People with diabetes who have difficulty controlling blood glucose are at greater risk of dying than if LDL cholesterol wasn’t perfectly controlled. I know that is complicated. The gist of the message seems to be that following the guidelines blindly may not be the ideal way to treat an individual patient. The authors conclude:
“Further research is needed to form a risk-tailored approach to balancing the cardiovascular benefits of statin therapy with its risk of diabetes progression.”
Amen to that!
We started warning our readers in 2003 that statins might make diabetes management more challenging. That’s when we received this letter:
“Recently, our physician prescribed Lipitor for my husband and myself. We both have been diagnosed with type 2 diabetes. We both take glyburide and my husband takes Avandia as well.
“Since we started on Lipitor, our blood sugar has been rising rapidly. My husband asked the doctor about changing to Tricor, but he was told it would not help him much and he should stay with Lipitor. It seems that Lipitor is affecting our blood sugar. Is this possible?”
“We searched the official prescribing information and discovered that ‘hyperglycemia’ (elevated blood sugar) was mentioned in a long list of possible adverse reactions. For the most part, though, this complication appears to have been overlooked.”
Fast forward almost 20 years and I would have to say that the association between statins and diabetes is still being downplayed. If you would like to learn more about this adverse drug reaction, here is a link:
Do Statins Cause Diabetes? Many MDs Wish It Weren’t So!
Most people know that statins can cause muscle pain and weakness. Not that many realize that there is now enough data to suggest statins cause diabetes.
Share your own experience with statins and diabetes in the comment section below. If you think this article is worthwhile, please share it with friends and family.
No one should ever stop any medicine without medical supervision, but people need to know that statins can impact blood sugar regulation.