In patients taking PCSK9 inhibitors, those with familial hypercholesterolemia developed new-onset diabetes at the same rate as those without this genetic condition, indicating that the genetic...

Pro

Against

Mechanism

Synthesis from 1 study

How it works

This drug lowers cholesterol by making liver cells grab more of it from the blood, but it also makes insulin-producing cells in the pancreas grab more cholesterol too. Too much cholesterol inside those cells makes them less able to release insulin. Only people who already have high blood sugar...

Most probable mechanism

In Simple Terms

When a drug blocks a protein that normally removes LDL receptors, more receptors appear on the surface of insulin-producing cells in the pancreas. These extra receptors pull in more cholesterol from the blood, which builds up inside the cells. Too much cholesterol inside these cells makes them work poorly, so they release less insulin. This problem only leads to diabetes in people who already have high blood sugar before starting the drug, because their cells are already struggling to manage glucose.

Causal chain

PCSK9 inhibition increases the number of LDL receptors on the surface of pancreatic beta-cells

Not yet directly tested

which leads to

Increased LDL receptor density enhances low-density lipoprotein uptake into pancreatic beta-cells

Not yet directly tested

which leads to

Intracellular cholesterol accumulates in pancreatic beta-cells due to elevated LDL internalization

Supported by evidence

which leads to

Cholesterol accumulation induces cellular stress and impairs insulin secretion capacity

Supported by evidence

which leads to

In individuals with pre-existing elevated fasting glucose, beta-cell dysfunction progresses to overt diabetes

Verified by multiple studies

Evidence from Studies

Supporting (1)

Community contributions welcome

Impact of PCSK9 inhibitors in glycaemic control and new-onset diabetes

Cohort Study

Human

Contradicting (0)

Community contributions welcome

No contradicting evidence found

Gold Standard Evidence Needed

According to GRADE and EBM methodology, here is what ideal scientific evidence would look like to definitively prove or disprove this specific claim, ordered from strongest to weakest evidence.

Source Study

Impact of PCSK9 inhibitors in glycaemic control and new-onset diabetes

Score: 56

DOI: 10.1186/s12933-023-02077-y

Similar Assertions

People in Saudi Arabia with a rare cholesterol condition don’t seem to lower their bad cholesterol as much with a certain drug as other people did in past studies — and it might be because of their genes or how the treatment is used in real clinics.

83%

People with a rare genetic form of high cholesterol caused by two broken copies of the LDLR gene don’t get much benefit from PCSK9 inhibitor drugs — most see almost no drop in their bad cholesterol.

81%

People with a rare genetic cholesterol disorder who still have a little bit of working cholesterol-cleaning system in their body tend to respond better to a certain type of cholesterol drug, lowering their bad cholesterol by about 20% on average.

79%

People who naturally have lower activity of a protein called PCSK9 don’t seem to have a higher chance of getting type 2 diabetes — which means drugs that target PCSK9 might not increase diabetes risk like some earlier studies worried they would.

76%

For people with a rare cholesterol condition called HoFH who are already on cholesterol meds, adding a newer drug (PCSK9 inhibitor) barely lowers bad cholesterol for most — and 7 out of 10 don’t get enough benefit to keep taking it.

76%