When to start statin diabetes
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
viewers we hope you'll continue to
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