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Statin Intolerance and Diabetes Risk: What Do We Know?

greetings I'm dr. Thomas Allison I'm

director of exercise testing in sports

cardiology at Mayo but I've also worked

for many years in the preventive

cardiology clinic I'm joined today by my

colleagues dr. Francisco Lopez him and

Eze who's the director of preventive

cardiology in Mayo and doctor of ania

simba who's an endocrinologist and

specialist in lipid ology welcome guys

thank you okay

so we're going to talk today about

statin intolerance and and first of all

is a lot of patients complain of this we

see patients all the time

is this real and if so how common is it

well that's a very good point it seems

to be real there are so many patients

complaining of it every day and even

though the the idea has been

controversial in the medical community

it is so frequent that there seems to be

something going on there it is reported

to be about 5% of patients taking

statins might develop some symptoms that

can be attributed to the statins but I

think the problem is that we don't

really know how how bad the problem is

because most clinical trials actually

had this run-in period where they gave

me the medication to patients and only

those who came back with enroll in the

trials so unfortunately we don't really

have good like we didn't maybe get it

out the entire and on the other side of

the of the coin how many times do you

recommend that the patient increase

physical activity and start an exercise

program at the same time you prescribed

statin yeah very very frequently so I

suspect that the problem is real it

exists but unfortunately many patients

especially when patients are have this

preconceived notion that statins might

be harmful they might be more aware of

any little things or pains but by the

other hand that we're probably dealing

with something real that happens to some

patients and and the problem is how to

to identify the real right and have we

have we yet found a simple test other

than talking to the patient is there any

lab test or is there anything we can do

to to distinguish between the patient

who's just complaining and somebody that

really is reacting to the stand well I

mean we have traditionally been using

the CK levels and clearly we have

realized that you can have statin

induced myalgias and even Myositis in

the absence of biochemical evidence of

muscle damage so I guess the short

answer is no there will be people where

you cannot by chemically establish that

there is statin induced muscle damage

but now you're in the research studies

we have set a very high bar in the sense

you know unless somebody has over a

ten-time elevation in CK levels we don't

label them as having statin induced

Myositis I think in clinical practice

that's probably a very high bar and I

will never be comfortable if my patient

has like a 3-time five-time elevation

and see Kayla well that would certainly

make me nervous I think it's a clinical

diagnosis essentially if the symptoms

start soon after the patient starts

taking the medicine if they go away when

the patient is stopped the medication

and they recur when we try another one I

think we can confidently maybe back

notice what it is real or or the patient

has a lot of might be some bias or

something is hard to know but but I

think the clinical diagnosis

now another another current concern

about stands is diabetes and so we've

got somebody that's recommending a lot

of stands and we got somebody is

treating some diabetic patients so so do

the statins cause diabetes is this real

I think it's real the statins cause new

onset diabetes I think it is true but it

has a very small effect just to speak

numbers so the the most recent large

meta-analysis

about 17 trials had over 100,000

patients so and again it is not it is a

class effect but then it's not all

statins cost the same degree of glucose

intolerance so perhaps like with

pravastatin which is perhaps the least

gluco toxic of all the statins the odds

ratio is about 1.07 so there's about a

7% increase as opposed to say something

like rosuvastatin a twenty milligrams

causes a 25% increase so overall yes the

use of statins even when compared to a

placebo or high dose compared to a low

dose is associated with a small but

definite increase in the risk of

diabetes okay now so my BMI is maybe 25

or 26 I am exercise every day I try to

eat healthy if if Francisco puts me on a

statin am I likely again diabetes is it

is that the profile or who's likely to

get diabetes with it's not said of

Francisco do you want a statin if he

does a high thing you can breathe more

easily I your risk is much lesser than

somebody who is already predisposed to

get diabetes so this would be things

like somebody who is already though

interestingly the BMI did not play out

in all the meta analysis but that could

just be because it was diluted but it is

a common clinical practice that fasting

plasma glucose itself of course predicts

so people who already have impaired

fasting glucose people who have impaired

glucose tolerance these are at the

highest risk and they have also noticed

that polymorphisms and certain genes

which impact beta cell function so if

you have that deleterious polymorphism

you're more likely to get statin induced

you know onset diabetes so you know it

seems to be real but I think it's

important to put things in perspective

if statins increase the sugar or the

blue candy the fasting glucose level

this March and that moves some patients

from being pre-diabetic to diabetic I

think the clinical relevance of that is

is minima will be equivalent in the

opposite or in the

there's point of view that if a medicine

decreased the glucose level by five

units and moving you from being diabetic

to just pre-diabetic

that that will be an amazing drug and we

know that will not be true yeah so so

here's here's a question the new

guideline if if you sort of do the

calculation if you're a male and you get

to be about 62 or 63 years old you're

gonna reach that 7.5% and be a candidate

for statin therapy if you're younger and

maybe have a little high blood pressure

you're going to reach that an even

younger age which means we're going to

put a lot of patients on statin therapy

it is it worth the benefit I mean the

risk benefit of treating large numbers

of patients in their 60s and 70s with

statin drugs even though they don't at

this point have a diagnosis of coronary

disease is it worth is it worth the risk

with the diabetes and the myalgias so

just looking at the diet no you know

it's a very loaded question the way you

ask about I mean if it's a straight

question is is it worth treating statins

for primary prevention absolutely we

have had many trials but then in people

who are over 60 65 we don't really know

that I mean there are just really few

trials like prosper and so on which have

looked at the older people with respect

to diabetes it's like this so based on

the CTD meta-analysis so if you have

like about 250 people who treat with

statins for four years there will be one

new case of diabetes and during the same

period you would have prevented a

composite vascular event of 9 so it

would probably benefit nine people that

cause diabetes and one so on balance it

still appears there so benefit 9 risk 1

sounds like a very favorable equation

yes but this did not include just people

who are 65 and the meta-analysis

included both primary and secondary

now if the concern is that statins cause

diabetes because start is my increase

and the glucose level but we know that

in patients with diabetes

statins actually give a pretty strong

benefit I think that's a very good point

too to not be too concerned about this

increase in the sugar when the benefit

is going to be and that much yeah can

it's this is a complex topic but I want

a quick summary the patient comes to you

with stand intolerance what's your

approach well first of all I will try to

verify that that's it's real intolerance

I will ask a few few questions to the

patient and if I confirm that is indeed

it sounds like intolerance I will give

the patient I will first try a very low

dose of statins like five milligrams

Rosa was 13 perhaps 10 milligrams of

atorvastatin every other day and see if

the patient tolerates that those if the

patient has been on on different statins

and refuses to try that

I will then focus on very strict dietary

recommendations and lifestyle changes

any any role for intestinal acting

agents in this population that's a good

point

if the patient has a high LDL

cholesterol I will certainly try

trying medicate other medications to

lower cholesterol but if the LDL is not

high I will then focus on non

cholesterol drugs well yes so I would

use the c-word but then the other hand

the well call good call Sevilla so we as

endocrinologists have a lot of interest

in this because the bile acid binding

resins they also lower glucose so if I

have somebody who and as it is we are

worried about increasing the risk for

diabetes so using a bile acid binding

resin and a statin intolerant patient

would probably help lower both glucose

and LDL

so we do use that quite often the

healthiest people in the US are the

seventh-day Adventists who follow a

plant-based diet do do either of you

recommend a plant-based diet to your

patients with hyperlipidemia that don't

want to take statins or or can't take

stands yes I think that goes without

saying I mean whatever we do in terms of

stat in any pharmacotherapy is an

adjunct to lifestyle changes and yes of

a be not a vegan but at least a

plant-based diet but a lot of

phytosterols 10 are Lester's I think it

would be very beneficial and I strongly

emphasize that yeah and the other thing

is that is important to to keep in mind

and this is in the preventive side is is

to avoid high intensity starting

treatment in the elderly and also being

very careful with patients with chronic

kidney disease and particularly in

patients who have some history of muscle

problems or patients with Rheumatology

conditions where they may be more

sensitive to high-dose statins and might

develop either symptoms or actual

Myositis one last quick question poly

pill trials are going on around the

world poly pills are advocated

particularly in developing countries

that may have limited resources for

traditional office based medicine and

and a lot of laboratory work in checking

risk factors do you think that these

concerns about myalgias and diabetes

should should derail the poly pill

approach or is this a still valid

approach I believe it is still a valid

approach the poly pill generally implies

a lower dose generic statins and you

know you have always simplified things

by calling statins as diabetic genic

there's actually an ongoing trial of a

bit of a statin called

j predict in Japan which is trying to

see whether a bit of a stat and reduces

the incidence of diabetes so I don't

think that all statins

in a bad and a smaller those in a

quality participant it was kind of

surprising because didn't the one of the

first stanton trials the west of

scotland trial

yeah I hate show the opposite effect

that there was a reduced risk of

diabetes with this 40 milligrams of

pravastatin exactly exactly though it

kind of caught us by surprise didn't it

yes the wasps cops actually showed that

though of course the definition of

diabetes in wasps cops was an increase

in glucose by two millimoles and not but

nonetheless yes it's not that all

statins cause hyperglycemia Francisco

benaiah like to thank both of you for

your contributions and insights on this

interesting timely and controversial

topic and thanks also to all of our

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