When to start treatment for type 2 diabetes
Insulin Treatment in Patients with Type 2 Diabetes
thank you for coming for the this
webinar the webinar is going to be about
insulin titration and insulin initiation
by dr. imperious that is the professor
of Emory School of Medicine and the
division of an endocrinology and work
here at Grady Hospital I will just want
to let you know that the webinar for
next month is going to be June 19th
about management of hypertension in
patients with type 2 diabetes now we're
going to talk about insulin treatment
patient with type 2 diabetes
thank you those shares well thank you
Lena thank you very much who all of you
for joining today in this very important
webinar we have over a hundred
participants around the country so it's
great and and as enough mentioned the
next time in June 19th we're going to
discuss about hypertension the new
guidelines they are so confusing the
West the goal target and what agents
should be to be used for the management
of hypertension so today we're going to
discuss about insulin tree and now and I
hope that this presentation is very
practical when do you choose what to
choose and how do you go to a judge and
of course there's also how do you
combine insulin with other agents
especially when glucose control is not a
chief let me start with this I mean I'm
a member of the professional practice
recommendation committee of the a DEA
and I chair the diabetes counseling
guidelines committee for the American
College of endocrinology we receive
funding for investigating share studies
when different companies money goes to
Emory otherwise I have no direct
conflict with any other pharmaceutical
company so when you talk about insulin I
think is good to keep in mind what
happened with better self function or
insulin secretion the impatient with
type 2 diabetes
and this is data that is derived from
the United Kingdom perspective really
studies in which you can see is that at
the time of diagnosis of diabetes which
see in the x-axis with the number 0 the
it is estimated that about half or the
beta cell function or the capacity to
produce insulin is gone in the patient
with type 2 and with progression of
diabetes the insulin secretion
diminished and the reason why this
happen is because the better
self-effacing with type 2 diabetes
undergo apoptosis of cell death more
rapidly than a patient without diabetes
so the main reason why people develop
type 2 diabetes is the inability of the
pancreas to produce enough insulin to
overcome the insulin resistant
associated with obesity so when you look
at at the beginning if you have a
patient with type 2 and you diagnosed
them early like pre-diabetes diabetes in
that phase it's very easy to control
them you had the best actor in the world
lifestyle will do it or mono therapy
with mono therapy with metformin that is
the preferable prefer agent but will
increase the racing of diabetes
metformin is not enough or sulfonylureas
of the agents are not enough and most of
the time we're going to require
combination therapy so when that this
combination therapy is needed well it
varies from patient to patient but after
3 to 6 months that somebody's not well
controlled use of combined agents and if
you look at this lives after age 9 13 to
8 to 10 years of of diabetes most people
are insulin opening so we tell our
patients that sooner or later that very
likely in the natural history of the
disease they will require and this is
where we have to accept as
and it's not that the patient is not
control because they don't take care of
themselves it's just the natural history
of the disease so in the last two years
in the last few years really this is the
ACE recommendations you see that the
first thing that we recommend is to star
or a legends lifestyle therapy for
everybody and then we go to mono therapy
and we would like everybody to be
treated with metformin because it's as
effective as most of the other medicines
is safe we have 40 50 years experience
abusing as cardiovascular protection and
if metformin is not enough three months
later we would like you to combine
metformin with G up to 180 LT 2 DP
before or all the other agents that you
see in this slide the other thing here
to your right is when does insulin is
needed so if you have a patient with a
couple of oral agents or more
importantly if you have the patient with
symptomatic diabetes so with polyuria
polydipsia weight-loss they are carbolic
because of the hyperglycemia you must
consider insulin in patient with type 2
diabetes we would like you always start
metformin in combination with basal
insulin anything under and that's the
best way to do it and metformin is
important when you start insulin because
metformin reduces the need for insulin
but about 20 to 30 percent so the
insulin dose that is requiring a daily
basis is Markley diminished with
metformin
so if I have a patient for example that
present to my clinic with glucose at 3
400 I would start metformin 500
milligrams twice a day with meals and I
peeve an insulin a basal insulin once
daily that we will discuss in the next
few minutes when do I use basal balls
only for type 1 diabetes
okay so had been
meeting with hyperglycemic crisis but
let's review how we start insulin
therapy so these are the recommendation
of the American Diabetes Association and
the American cause of endocrinologist at
we said before you start with lifestyle
changes plus one or two oral agents and
then you go to basically insulin therapy
following that how much and here is
basically insulin we would like you to
consider analog on top of NPA's however
NPH works well if you decide to use
analog the American College of
endocrinology will recommend you to look
at the hemoglobin a1c of the pace if the
hemoglobin a1c is less than eight so if
somebody's taking one or two oral agents
who contrast our insulin they were
starting point one to point two units
per kilo so it's somewhere around 6 to
12 14 units for most people and if the
hemoglobin was seized greater than eight
percent eight nine ten you start on
point 2 to point 3 units per kilo so
when do you use the point to where
elderly people patient wise home keep
the kidney compromise I'm point three
for the more of these younger patient
normal kidney function so if somebody
like me that I'm about 80 kilos I will
start myself on 20 units of insulin once
daily in combination of the oral agents
and this is shown in this life so rule
number one is that you continue the oral
ages second you are and even those of
NPH
can also be large in order a meal or
take later and you start on point to 0.3
in is pretty low and what you're going
to do you're going to look at the blood
glucose next morning the fasting blood
glucose so if you use mph that is very
good insulin in patients who are normal
kidney function eating well you're going
to start on point two point three so 20
years or 15 years and you look at the
fasting blood glucose and you'll then
you're going
to adjust the insulin daily or every
other day with twice a week increasing
the dose of insulin till the fasting
blood glucose is within your range in
this case less than 130 could be less
than 150 do you have to decide what the
fact in glucose targets should be so why
if you use NPH you must give it at the
even in those because of the short
half-life of the MTA's insulin and when
you are in your mind what you're doing
is to regulate the exaggerated hepatic
glucose production that is present
overnight in patients with type 2
diabetes if you are using large in for
you 100 you 300 if you use in datameer
or deadly tech you can give the insulin
dose at any time during the day in a
patient with type 2 diabetes
do you give 10 20 units of insulin at
any time and you talk to the patient and
ask what is preferable for each
individual and then you continue the
oral agents and these are declared in
third
so when you talk about basal insulin you
have the human instruments or mph that
have been around to the 1950 you have
the analogs the loan act in analogs then
you have large and you 300 you 100
datameer you 100 and we have also basic
law of biosimilar that is also you 100
and in the last five years we have the
law knocked in insulin that is you 300
they will take you 100 or you 200 so you
have a large number in reality we have
12 different formulation of insulin for
the treatment of type 2 diabetes so here
at this table and the table shows the
characteristics of each one of these
agents human instantly started working
in two to four hours impeaching about
four to ten it varies from patient to
patient then it has a duration of action
between 12 to 16 hours there are mirror
and large are not very similar
Guardian has a little longer duration of
action but not much different and in
contrast to the nth it doesn't has a
pronounced peak and this is shown in the
bottom on the different graph that we
see in this live and this is the mph the
problem with the mph that has a peak but
it worked well but the variability of
day to day is much larger than the
Damier show in the middle or the large
and shown in the right lower quadrant of
this line so how good is in pH in pH
worked very well and we have used mps in
combination with metformin for the last
40 years it has also been shown in
combination with sulfonylureas although
the reso hypoglycemia is higher if you
use MPs and sulfonylureas what you see
in these lines is data from Europe from
all data 20 years ago that is if you
have a patient take a bit time in pH
with oral agents and you see that they
reduction with metformin and MPs is
somewhere around 2 to 2.5 percent given
impedance at plates on the mph twice a
day so it worked very well
you start 15 20 units of NPH 20 no
metformin and it works very well in the
last few years in the last 12 years we
have the data from large in u-100 under
Emir and if you compare mph what is
shown here to the left versus large n
there is no difference in glycemic
control so if you titrate in pH at a
time or guardian at that time or any
time during the day and you increase the
dose progressively to achieve good
glucose control there is no different so
the efficacy of mph and Largent is very
similar and the same thing it could be
compared to their Amir in the right side
of this line but if you compare these
safety so the hypoglycemia risk between
NPS and large in or in
and their mission to the left large and
showing to the right and if you try to
achieve a fasting blood glucose less
than a hundred less than 110 you have
more hypoglycemia so if you're going to
use in pH you should not try to get yeah
you should not target a fasting blood
glucose less than 100 110 120 our target
a blood glucose fasting blood glucose
less than 140 in that case I don't get
much hypoglycemia but if you use the
analogues you can titrate through lower
blood glucose in the way that you have
less hypoglycemia so again this is how
you start in pH in the evening large and
at any time during the day you start
from 1 to point to a point two point
three dependence or hemoglobin a1c but
if you stop are let's say 15 20 units
for a patient with type 2 that's likely
it's not enough but you want to start at
a low dose because you want to prevent
hypoglycemia if you start in the higher
dose and the patient star will develop
hypoglycemia they get scared and we know
that patient have recurrent hypoglycemia
they don't titrate and they lose control
so what we want is to start low dose and
ask the patient to selfish-ass danger so
we tell the patient to increase the
insulin dose by 2 to 4 units every 3 to
5 days and the person can do that
himself and you have to teach him I ran
in the piece of paper the blood glucose
greater than 150 180 every day you
increased by 12 you two units hotel you
start on 20 you go to 22 24 26 every 3
to 5 days until you achieve goals there
are some other ways to do it you can
increase by 10% in the blood glucose
between 140 to 180 or by 20% the total
glucose total insulin those if the
fasting blood glucose greater than 180
it doesn't matter what formula you use
the patient should learn how to adjust
insulin therapy and
of course if you start 10 to 20 units is
not enough for it and this has been
shown in different studies like this one
that depicts the amount of insulin in
different studies the internal insulin
dose is somewhere around 40 to 80 unit
for most people so if you start with
just 10 20 units they need to self
adjust and this is important because in
most of the clinical studies for example
this is a meta-analysis in almost 17,500
patients the chances that somebody using
oral agents and area basically
instruments is not very good most people
do not achieve good glycemic control
only fifty percent but this is important
to keep in mind and you have to tell the
patients because the patient are
expecting that if you start insulin
they're going to be in control but
unfortunately not everybody achieve
control so you need to titrate the dose
up and of course keep in mind and the
patient should keep in mind that maybe
this is not enough and you need to have
combination therapy so why is not enough
because basal insulin control the blood
glucose during the night during the
fasting space and before meals but it
doesn't cover the postprandial glucose
excursion so if I have somebody taking
metformin is a sulfonylureas or
metformin
and you add insulin I'm going to control
the base so I'm going to control the pre
meals are going to control the overnight
low glucose but it's not going to
control the postprandial glucose
excursion and what is shown in this lies
is that the higher the hemoglobin a1c
they higher the pigs offering after
meals so if you have somebody on day so
insulin not enough you have to control
postprandial and how can you control
postprandial well you can do it with
insulin or with other agents so you can
change the patient to premix insulin or
you can are based on price or base of
also multiple those
insulin combination of basil and
rapid-acting insulin or more importantly
what we do right now is combine the
insulin with other agents so this is the
Emory algorithm that we tell our
patients how to manage patient with
premix so we start 70/30 insulin
remember this is can be analog - it can
be human insulin a human insulin is just
$25 a month a analogues are much more
expensive and if somebody you're going
to start on a 70/30
the patient is symptomatic we start on
point 2 to point 3 units per kilo and we
divide we give 2/3 of the dose in the
morning one fare in the evening so if
I'm going to start somebody on 30 units
of insulin and we start 20 units in the
morning 10 units in the evening and they
my going to ask the patient to attach
the insulin every buy two units in the
mornings on at 9:00 every two to three
days and more importantly I'm going to
continue the oral agents in most of
these places so how good is 70/30
compares to Largent with it earlier here
to the left this is study on 371 patient
with type 2 diabetes on a combination of
oral agents and you add of premix or
Largent to see that the glucose control
is very similar insulin is insulin and
bring the blood glucose down but to the
right is the rate of hypoglycemia and
you have more hypoglycemia with 70/30
compares to margin yes do titrate to a
blood glucose less than 100 110 this is
another study from Phil Raskin
in Dallas and it's also shows that they
have more hypoglycemia with premix
insulin compares to Arjun however the
other studies more recently that shows
if you don't titrate that aggressively
the difference is not much different so
you can also do low knocked in a
combination of Lord Acton and prandtl
insulin so what we call basal bolos
approach so the rapid acting insulin so
the least grow the a sporadic blue
lysine is giving before meals they pick
quite rapidly in about twenty to thirty
minute and prevent the glucose is course
enough for a meal and you keep the basal
insulin once daily so in the past we ask
the patients in baseball
most of the time what we would like to
do is what is called do a step
transition from basil to basil plus one
plus two plus three that means that you
keep basal insulin the same dose and you
are five to ten units of insulin before
the largest meal it doesn't matter now
if you go to the second largest meal it
has I don't know if you go to the full
bone base footballers approach given
basal insulin plus rapid acting insulin
before each meal and this is what the
American College of endocrinology
recommend you started the basal + 1 + 2
+ 3 + u star on five units for 10% of
the basal dose given before each meal
and you progress to how a 50% base of
50% brand of insulin and there is a
large number of studies that have shown
that glucose control is very similar if
you do from biggest balls or do progress
from basil one plus one plus two plus
three so how cool is baseball this booze
is excellent in the way that you will
increase the chances that somebody will
call from basil only 50% achieve goal if
you go to baseball is about 2/3 or 3/4
of the patient with a cheap call not
everybody not everybody but baseball is
much better but has some inconvenience
that's right the inconvenience is going
to be multiple injections of insulin per
day and patients don't like that second
weight gain in the way that insulin
tried to gain weight
tends to present an insulin game way so
- around two to three kilograms in
average and there's the reso
hypoglycemia so this is what we have
behind until very recently the analog
Delamere of collagen or the human
insulin analogs premix in the last few
years we have this lawn acting insulin
let me quickly review them for you so we
have large Indy 300 and we have de glue
take you 100 and do 200 they have a very
long half-life of about 24 hours for
Arjun and about 40 hours a 40 hours 36
hours for large in about 40 hours per
day gluten and what is happening is that
it steady state is achieved later but
the peak is very flat so it's very good
in the way that give you it's easier to
take the insulin if you don't take it at
age you can take it at 12 midnight or
even in next morning with good control
so large in you 300 it has low in
half-life duration of action about 36
hours and here you have comparative to
insulin glargine you 100 in blue is you
300 the effect is very flat must fly
flatter than patient with you 100
insulin therapy
so there are similar studies in type 1
and type 2 diabetes and if you compare
the efficacy so the ability to reduce
insulin he the hemoglobin a1c between 13
to 100 and large and you 300 there is no
difference but the rate of hypoglycemia
is much less with Clark and you 300
compared to you 100 days there are
several studies in patient with type 2
diabetes and impatient with type 2
diabetes and all of them has
that the efficacy in reducing hemoglobin
a1c is very similar to the you 100 and
in most series you decrease the
hemoglobin a1c between four and eight to
one point five milligrams so if you want
to change you 100 to you 300 to improve
glycemic control Ron you won't get that
they were as shown in this lies is that
several studies have indicated that you
300 because of the flat effects the long
duration of Marchen the rate of
hypoglycemia is reduced by about 15 to
30 percent
especially nocturnal hypoglycemic so the
reason why you will choose you 300
instead of you 100 is because of the
reduction in hypoglycemia it comes also
only in pens we don't have it in
syringes and if you want to change one
somebody from you 100 to 300 you do want
to want those conversion so you don't
need to change the dose just change the
device so what about instantly
definitely that's the new insulin and
newer insulin who has a duration of
action of I mentioned before about 40
hours half-life 3 24 25 hours and you
can be take insulin up to five days
after injections and the effect is very
flat as shown in this slide this is the
Lucas lowering effect and you see that
doses of point four point six point a
passing change so it doesn't have the
peak that we see with their Amir and we
see with larger so again if you want to
change you 100 or even ampere is too big
with it you don't do it because of you
want improve glycemic control the effect
is the same as shown in these lines in
the right upper quadrant in the left
upper quadrant
that is a short that is equal the
reduction hemoglobin a1c yeah you
titrated those until hemoglobin a1c
comes down the will is shown here in the
right is the rate of hypoglycemia and
the deck has been shown to significantly
reduce hypoglycemia compared to all of
the other incidents including you 180 it
comes in two concentrations in new 100
so 100 units per ml or you 200 200 units
per ml so good in the you 100 you can
deliver up to 80 unit per injection the
other up to 160 units per injection the
price is very similar and if you compare
you 100 with dignity a big lead egg has
significant less hypoglycemia as shown
in this devote trial pound is about a
couple years ago in that it showed that
you reduce hypoglycemia and it would be
the same for mph that's right
so Rajan is better than MPs and
reduction of hypoglycemia
Diglett egg has less hypoglycemia
compare it to you 100 and if you compare
you 100 and you 300 and dignity there is
no difference in the effects or the hypo
recipe so should we use what insulin so
we use one of the major problems that we
have especially in many areas and I work
a Grady Hospital with 32 percent of my
patient have no insurance so what about
cost classes have important factor as
shown in this life because of insulin
has increased significantly during the
last twenty to thirty years but they are
insulin especially the human insulin the
regular the NPA's the premix insulin a
70/30 with MP a 70% regular 30% that you
can get it by $25 of Walmart and inseong
pharmacies so human insulin is still
relatively cheap but if you look at the
cost of analogs
the class is somewhere well over two and
three hundred
and in many save in many areas is even
much higher so this is something that I
use I use a lot of 17th 800 mt/s at
bedtime or 1730 twice daily in many
patients and start on point two point
three units and I divide and I've
progressed if the patient have no
insurance so a the good thing about
basic policies that they achieve control
but it has multiple injections so what
do you do if the patient offer based on
insulin is not well control again just
to remind you that is because of the
postprandial glucose excursion so you
need to cover post Brando and the way to
cover post prandial is given multiple
injections a day or the other thing is
to combine basal insulin with a top-1
receptor agonist a dpp-4 or an SEO t2
inhibitors all these three ways three
regiments are effective in controlling
postprandial glucose is cursing so the
first one is top-1 this is my favorite
they are right now studies comparing
going from basal to basal follows from
basal plus one glp-1 daily or every week
and the glucose control is exactly the
same so why is that because glp-1 works
in multiple ways
it increases insulin secretion second it
reduced glucagon secretion so decrease
glycogenolysis or exaggerated hepatic
glucose production a slow down gastric
emptying so your sugar your glucose is
coarse enough for a meal is delay and of
course it's associated with decreased
appetite because of the central effect
of the top-1
in the brain so
combination of basil and GOP wine is
very attractive
GOP one has been shown to improve
hemoglobin a1c and the left decreased
body weight and merkley decreased the
insulin dose because your crew coach is
better and you have a delay in gastric
emptying it can be given once a day it
can be given once a week and there are
several once daily liraglutide the most
commonly used they live
top-1 but there are several once weekly
medications and we have a external time
once we click do like retire or
trulicity once weekly and we have
semi-retired once weekly so you need to
basil every day and once a week glp-1
these studies shows the combination of
large in bursts with placebo margin with
excellent times in yellow and you see
that the addition of exenatide
markley improved less in control by 2%
without the weight gain that we see with
basil paulo therapy so the combination
of basil and GOP one is really great
this is another Spanish that is called
LIXIL on all in which patients were
receiving oral agent and with a
randomized to receive glargine in blue
links is an entire say top-1 in orange
and the glargine mixi in black and this
is the only way that you can achieve
racemic control with hemoglobin a1c less
than 7% here you have the starting with
the hemoglobin we see about a 8.2% the
end of the treatment at 30 weeks 26th
week the hemoglobin a1c was reduced a
6.5 without an increased risk of
hypoglycemia the other thing is that we
discussed in previous meetings is that
the GOP one has been shown to be cardio
protective
and for example this is the use of
liraglutide in the leader trial the
adding to oral agents another two
medication for diabetes it reduced the
maze outcome that included
cardiovascular death non-fatal marker
and partial or stroke so and this is
another study with similar type that
also reduce cardiovascular events so the
combination of basal insulin with
chilled pea one is the preferred way to
manage patient and instead of going to
play football the third so baseball's
premier care used love baseballs
endocrinologist do not put patient with
type two the different storage patient
with type 1 so baseball has great
efficacy most people achieve goes about
2/3 of them and we are used to do it but
basal plus top-1 have similar efficacy
at less injection that the three
shot-for-shot today they have low entry
so I pulled the Samia no weight gain and
may have cardiovascular risk with our
team
so cons or adverse experience baseball
have hypoglycemia weight gain
cardiovascular neutral if the GOP one of
course has the main problem that I have
is a GI adverse events about 30 percent
develop lost year during the first
couple weeks and cost cos is always a
big time consideration so what about DP
before an ACL - how well do they cover
for surrounding of glucoses course and
here you have data when they'll use OTP
before the DP before
works mainly in the post prandial state
so it could be basal with DP before
you're going to decrease the glucose
excursion after a meal and that's why
you reduce hemoglobin a1c and it's
weight neutral and cardiovascular
neutral so there are several studies
combining
Ezio today VP before an insolent I'm now
you said a lot especially in elderly
people with the hemoglobin a1c less than
8% the Amerigo I may add a bit before
you can also try the alt two alt to work
by flashing glucose in the urine
flashing sodium in the urine has
cardiovascular protection but also
covered post Brando and here you have
the effects the combination of a co2 to
plus basal insulin okay a great effects
I'm somewhere around pronate 21.5% a
more important with no increased risk of
hypoglycemia
so excellent medications to be used in
patient with insulin so in this line and
what this is my bias and I think
represent where the American College of
endocrinology and the American Diabetes
Association will suggest what to do so
you start life changes your admit form
and you combine or relations and then
you add basal insulin and in the past we
went to basal insulin to basal follows
there is no question that right now
anytime that I see a patient with type 2
after basal insulin and we going to base
or black teal t1 or dpp-4 initial T 2
because this agent do not produce weight
gain and maybe cardio protective I hope
that this lecture has been practical and
helped you to manage patient with
diabetes the things to keep in mind are
1 diabetes is a progressive disease
characterized by diminishing
beta cell function due to beta cell
apoptosis we decrease better cells where
the cells that make insulin in the
pancreas so you start with one to peel
the three peels and at the end you must
consider insulin therapy if the
hemoglobin a1c is not our goal basically
insulin is when we recommend and it
could be NPH
at nighttime and in the evening or one
of the analogues at anytime during the
day you can also use 70/30 or premix
insulin in most of the patients starting
point two point three units per kilo and
do titrate up because the usual dose is
much more than the point two point three
kilos that a patient would require if
basal insulin is not enough you might
our insulin increasing agent you can go
to base of balls multiples injections a
day well I will call you to think that
maybe the insulin plus co2 one or dpp-4
may be better in most people the same
night as your t2 maybe better than the
use of a base of power therapy
now keep in mind one thing that most
people most people will will need
insulin sooner or later in during the
lifetime of a patient with diabetes
patient who has symptomatic diabetes
should be on insulin therapy that
doesn't mean and always combined with
metformin if you're going to start based
on internal Baseball's insulin because
that reduces the insulin requirements
during the day I appreciate your
attention and you can get credit and you
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