August 26, 2025 • 35 mins
In Episode 49 of Think Like a Pancreas—The Podcast, host Gary Scheiner is joined by Integrated Diabetes Services clinician, Dr. Paula Diab. Together they discuss the off-label use of type 2 diabetes medications in type 1 patients.
Paula and Gary describe the hormonal balance necessary for blood sugar management and how the off-label use of medications like metformin, GLP-1 receptor agonists, and SGLT2 inhibitors can help.
During their conversation, they emphasize the importance of patient education and informed discussions with healthcare providers regarding medication options.
Meet Your Host and His GuestGary Scheiner, MS, CDCES, is the award-winning author of Think Like a Pancreas as well as numerous other books that act as guides for people living with diabetes. A Certified Diabetes Care & Education, ADCES Fellow, Masters-level Exercise Physiologist, and person living with type 1 diabetes since 1985, Gary was named 2014 Diabetes Educator of the Year by the American Association of Diabetes Educators. He trained at the Joslin Diabetes Center and has dedicated his career to helping others live well with diabetes through education, advocacy, and innovation.
Dr Paula Diab PhD, CDCES is a Family Physician and Diabetologist who runs a multi-disciplinary practice specializing in the management of chronic diseases, particularly diabetes and obesity in South Africa. Her approach is to walk the journey with her patients and to allow them to manage their disease rather than allow the disease to define who they are.
Despite carrying the burden of being the only member of the IDS clinical team without type 1 Diabetes, her skills and passion for diabetes care & education are exemplary (she did successfully manage her own gestational diabetes during her pregnancies).
What you will learn:✔️ The role of other hormones in managing type 1 diabetes
✔️How biguanides, SLGT-2 inhibitors, and GLP-1s work in people with diabetes.
✔️What is double diabetes?
✔️ The safety of metformin use for people with diabetes
✔️ How to safely use SLGT-2s when you have diabetes
✔️ The benefits of GLP-1s.
Chapters
00:11 Welcome and introduction
02:19 Gary Scheiner--ADCES Fellow
02:50 Meet Dr. Paula Diab
05:20 The hormones involved in diabetes management
09:19 Why are there so few medications available to manage type 1 diabetes?
11:27 Understanding off-label use of diabetes medication
14:44 Type 2 diabetes medications that are prescribed off-label to people with type 1 diabetes
28:17 The best candidates for biguanides, SLGT-2 inhibitors, or GLP-1s use.
30:57 What to do if your doctor is uncomfortable prescribing drugs off-label?
Resources Mentioned
https://pubmed.ncbi.nlm.nih.gov/28615149/
DEPICT study – SGLT2 inhibitors (dapaglif) in T1D https://pubmed.ncbi.nlm.nih.gov/30352894/
EASE study – SGLT2 inhibitors (empaglif) in T1D https://pubmed.ncbi.nlm.nih.gov/30287422/
Liraglutide (GLP-1 RA) Trials in T1D
https://www.thelancet.com/journals/landia/article/PIIS2213-8587%2815%2900436-2/abstract
Semaglutide (Weekly GLP-1 RA) Trials in T1D
https://pubmed.ncbi.nlm.nih.gov/39794615/
Connect with Us🔵Website: integrateddiabetes.com
🔵 Follow on Social Media: @integrated_diabetes_services and @ integrateddiabetesservices on Facebook
🔵To work with the Integrated Diabetes Services Team , visit https://integrateddiabetes.com/how-to-start-the-process/ , or email info@integrateddiabetes.com
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Disclaimer
The information contained in this program is based on the experience and opinions of the Integrated Diabetes Services clinical team. Please dis
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Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
(00:11):
Welcome to Think Like a Pancreas,the podcast where our goal is to keep
you informed, inspired, and a littleentertained on all things diabetes.
The information contained in thisprogram is based on the experience
and opinions of the IntegratedDiabetes Services clinical team.
Please discuss any changes to yourtreatment plan with your personal
(00:31):
healthcare provider before implementing.
Welcome everyone to ThinkLike a Pancreas--The Podcast.
I'm Gary Scheiner, owner and ClinicalDirector of Integrated Diabetes
Services and Type one now for 40 years.
I just hit my 40 year anniversary.
Proud to be your hostfor the program today.
The topic is type two diabetes medicationsfor people with Type one diabetes.
(00:55):
You think about it, you know we, we've hadinsulin now for over a hundred years and
it's still the only approved medicationfor the treatment of type one diabetes.
We do have Symlin, you know, the amylinhormone analog, but that's coming off the
market shortly 'cause no one was using it.
So we really just have insulinas treatment for-- approved
treatment for type one.
(01:16):
But when you think about it,you know, blood sugar management
is a multi hormone process.
In healthy people, there's a multitude ofdifferent hormones that are used to, uh,
keep glucose levels within a normal range.
So it really does beg the questionof why we only have one hormone
that we're using for type one care?
And keep in mind also that withoutproduction of the amylin hormone,
(01:41):
which is the case in people withtype one, it creates a significant
challenge for everybody to managetheir weight, their appetite, their
food intake, makes post-meal bloodsugars control a major challenge.
So this whole questionabout, what's the deal?
Why, why are we only usinginsulin in type one care?
And that's gonna be the topic today, andwe're gonna hear from a diabetologist
(02:04):
and, uh, also a member of the IDSclinical team whose expertise includes
the multidimensional managementof diabetes, Dr. Paulaa Diab.
So Paulaa, welcome.
I think everybody wouldlike to hear more about you.
Thank you.
Before I introduce myself, I havea feeling that I'm the first on
this podcast since you receivedyour fellowship for the ADCES.
(02:24):
And we were just chatting beforethe recording started and I said,
congratulations and, and in yournormal and assuming and humble way,
you don't think it's a big deal,but it actually is a very big deal
and it's a remarkable achievement.
So I just wanna say congratulations.
You're embarrassing me, Paulaa.
I appreciate that.
No, but it's a testimony to alifetime of dedication to diabetes
(02:46):
and it's very well deserved.
So congratulations.
So I'm as a diabetologist and a familyphysician, but I don't like to be
boxed into that little box because Ithink doctors sometimes just are well
known for writing scripts and sendingpeople on their way in 10 minutes.
And I think just like diabetes doesn'tcome in, neat little boxes, I enjoy
the creativity of finding differentsolutions for different people.
(03:07):
I think that's a bit of whatwe're gonna touch on today.
I think in order to do that, you needto understand the medication that
you're working with in order to exercisethat flexibility and that creativity.
I got my basic degree in medicine andthen I was launched into the world in the
middle of an HIV, um, pandemic and a ruralunderserved and under-resourced hospital.
So every time someone complains to me thatthe insurance won't pay and they can't
(03:28):
get access to medication, I always thinkback to those days and I think, well,
life isn't actually that bad anymore.
But yeah, then I completed my master's anda PhD and worked in the field of diabetes
for about 20 years and more recentlyin the field of obesity management.
And then about two years ago, decidedto study further and qualified as
a diabetes education specialist.
(03:48):
But I think I've learned more from the IDSteam than I ever have in the 20 years of
working in clinical medicine and diabetes.
And I think a couple of years ago if youhad asked me about this topic, I would've
said to you, no, type one and type twoare two very different diseases and
you can't mix and mash the medications.
But I think when you understand howthe drugs work and what they do,
(04:10):
that's when you can start to mix andmatch and, and be a bit more creative.
Yeah.
Paula, you, you came to us severalyears ago with an interest in
becoming a certified diabetescare and education specialist.
And yeah, it's not a, not a lot ofphysicians are interested in that and
I, I was very impressed by your passionfor the diabetes care field and you did
(04:34):
spend a lot of time with our team and, andthere was a lot of back and forth 'cause
clearly, you know, as a physician, there'sa lot we've learned from you as well.
But you should also mentionthat you're, you're a mom.
You've got, uh, how many--you've got three kids, right?
Two.
A son and a daughter.
It just seems like three sometimes'cause they've got so many
activities there're involved in.
It seems like thirty-three sometimes.
Yeah.
(04:54):
And, and you're in South Africa, so you'redoing this from quite a distance as well.
But you work with, um, our IntegratedDiabetes patients on weight management
and, keeping glucose managedduring, during that weight management
process, which is tricky, but youfind a way to balance all of that.
Yep.
Lots of balls in the air.
I'm the chief clown.
(05:16):
Yeah.
All right.
So I mentioned before thatglucose management is not
a simple matter of insulin.
You know, when the, when a healthy person,non--a person who doesn't have diabetes,
they manage their glucose through amultitude of, of hormonal balances.
Can you just kind of give us anoverview of what that involves?
Sure.
So I think when I'm explainingto my patients what I generally
(05:39):
say to them, I, I say, think ofglucose as fuel for your body.
So if you think ofputting gas in your car.
It's a similar sort of process and theaim is to keep that glucose between
about 70 and 125 milligrams per deciliter.
And you want the glucose to be insidethe cells and you want it to be stored.
So again, going back to the analogyof the car, you don't want the,
(06:00):
the gas sitting on the sidewalk.
You want it actually in the engine.
So it has to be in-- the glucosehas to be inside the cells.
So the key players that, that are involvedare the beta cells in your pancreas, which
obviously produce insulin, and that'sinvolved in the glucose uptake in storage
and in the alpha cells in the pancreas,which produce glucagon and that stimulates
glucose released from the liver.
(06:21):
The liver is kind of yourbuffer that's stores and
releases glucose as it's needed.
And then you've got your adipose tissueor your fat tissue, and then there are
various other organs, your muscles, um,and in fact also the brain that comes into
the whole mechanism, how it all works.
And basically what happens is aftera meal, the glucose gets pulled up
(06:42):
into the muscles and what's not beingused is then sent off to the liver.
Stored glycogen is synthesizedin the liver and it's stored.
And then between meals, when you're noteating, then the body can then pull that
stored form of glucose out of the liverand bring it back into usable form.
If that fasting state is prolonged, thebody is able to use amino acids, which
(07:04):
is proteins and various other substratesto, to produce glucose if necessary.
But that's topic fora whole other podcast.
And then there's other, there'sother hormones and that sort
of play a more supportive role.
Your, your increase in hormones inthe gut, and they amplify the insulin
release after meals as well asadrenaline, cortisol, growth hormone
(07:25):
that all impact onto that whole story.
You know, it's, it's kind of likethe thermostat in your house as soon
as your, the pancreas turns on thecooling system, so as your temperature
rises or as your blood sugar rises.
The pancreas turns on the, the coolingsystem, and insulin then moves the
glucose into the muscles and the fats inthe liver or to be stored or to be used.
And then when you haven't eaten for awhile, that temperature then starts to
(07:47):
drop and the pancreas then flips theswitch to glucagon and tells the liver to
release the stored glucose and to make newglucose, to keep things more comfortable.
And then there's, as I said,there's all the other gut hormones
and that, that interact to sortof balance it out a little bit.
Yeah, I often, I think about the caranalogy, the, the insulin driving the
glucose down and that's accelerating thecar, and the glucagon's like the brakes
(08:10):
to, to slow down that drop and help,you know, maybe bring it back up again.
But you mentioned, you know, there's alot of other hormones involved as well.
The amylin hormone, which is also secretedby the beta cells, helps to slow down the
appearance of sugar in the bloodstream.
Uhm, you know, it keeps foodfrom digesting too quickly.
It blunts appetite, so itplays an important role.
(08:32):
The adrenal hormones, uh, cause therelease of sugars into the bloodstream
whenever we're under any form of stress.
And that can be emotional stress, physicalstress, any kind of stress that can occur.
You know, and that's where the braingets involved, is causing the production
of those stress hormones when thesituation arises and the gut hormones,
(08:52):
which also regulate the movement offood through the digestive tract.
So the appearance of thesugars is regulated to a large
extent by other hormones.
So, you know, given that, you know,there are so many different hormones and
systems involved in blood sugar regulationand there are so many other medications
(09:12):
that can help to manage those for peoplewith type two diabetes, why are there so
few available for those with type one?
So I think it, there aremany different reasons.
I think one of the reasons is becauseof the primary difference between
type one and type two diabetes.
The primary problem in type onediabetes is that that thermostat
is not working and there's a lackof insulin being being produced.
(09:32):
And so you can't bring the glucose downand so you need to replace that insulin.
You've got an insulin deficiency andyou need to replace that insulin.
Whereas in type two, the keyproblem is that, is to do with the
sensitivity of your target organs.
And there are multiple ways toencourage these organs to either
become more sensitive or to utilizethe the glucose in a better way, or
(09:54):
to accept the glucose in a better way.
So I think that is the main reason,because of that underlying difference
in that you basically have togive insulin in type one diabetes.
I think also what plays into it hugely isthat the risk of diabetes ketoacidosis and
hypoglycemia is a lot greater in type onediabetes than it is in type two diabetes.
So you're very much focused on preventingthose highs and lows and you, there's a,
(10:18):
there's less wiggle room, should I say.
The Type one population is muchsmaller than the type two population.
Probably about a 90 10%split um, worldwide.
Now, if you're looking at doing atrial or you're looking at marketing
a drug that's gonna be cost effectiveand have a big population to take
it up, there just aren't the numberof people in Type one diabetes.
(10:39):
Yeah.
So a lot of it comes down to dollars.
Absolutely the pharmaceutical companieswanna return on their investment and it
is a huge investment to develop a drug,to test it, to submit it, to market it.
It's a huge, an investment, andthey don't always see the type one
population as large enough to help themrecoup that investment, unfortunately.
(11:02):
You know, the government'snot really helping at this
point in that regard either.
So we're counting on thefree market system to dictate
what drugs come to market.
And if there were 10 times as manytype ones as there are, yeah, there'd
probably be more, more medications, moretreatments available than what we have.
But I think having said that, the waythat we currently doing it, where we are
(11:23):
developing and marketing drugs for typetwo and then using them off-label in a
type one situation, um, we kind of do
Tell me more about that.
Off-label.
I want people tounderstand what that means.
So off-label, basically... so any drugthat's produced basically gets a package
insert attached to it that tells youhow you can use it, when you can use
it, what dosage, what the side effectsare, what the contraindications are.
(11:45):
So in other words, when you absolutelycan't use it, and which populations
you can use it with, which other, whatinteractions it's got with other drugs.
Although we doctors like to be quitecreative, we actually are bound by
those rules that come with each.
Which, and if you're using somethingoff-label, it means that you're going
outside of those boundaries that areprescribed in that package insert.
(12:06):
So what is happening at the moment ispeople are using type two, or drugs that
are developed in marketed for type twodiabetes, in the type one population.
And that's not always completely unsafe,and I'll explain, we can chat about that
a little bit later and which populationsand who you, you want to give it to.
But you do have to be careful fora number of different reasons.
(12:28):
Yeah.
So, um, off label, it, it soundslike, uh, you're, you're going against
the established guidelines that thegovernment at least has set for each drug.
Can you go to jail fordoing something like that?
How risky is it?
Generally if you explain to the patientand you document that you, you explained
(12:49):
to the patient you're using it off labeland certainly not in South Africa, I
don't think anyone's gone to jail for it.
I don't dunno about in the states.
We have a lot more lawyershere, unfortunately.
But yeah, I mean basically it is just,we, we do it quite often with pregnant
patients because you can't, it's veryrisky to run a trial in a pregnant patient
on a drug that you, you're not sure of.
(13:10):
But what tends to happen is peoplefall pregnant without really
knowing that they're not meantto be taking a specific drug.
And so by trial and error we realizeactually drug A can actually be
used fairly safely in pregnancy.
And that's kind of what's happening atthe moment with, with a lot of these
drugs being used in type one diabetes.
And if you also think about howthey work, you can sort of logically
(13:31):
deduce, okay, this one will besafe in these circumstances and I
can use that drugs fairly safely.
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(14:15):
So pretty much anything that's beenapproved by the FDA for any indication,
for any health state, any type ofperson, it can be also prescribed to
someone else in an off-label fashion aslong as the physician or the prescriber
explains the risks to the patientand the patient's willing to accept
(14:36):
those, and I guess that's documentedsomewhere that it more or less protects
you against, against legal action.
What are some of the more common drugs ordrug classes that are prescribed off-label
to people with type one diabetes?
Yeah, so I think at the momentthere's probably about three
different classes of drugs that we'reusing on a fairly regular basis.
(14:58):
The first one is, and I'll, I'llsort of briefly just go over each
of them and then we can go intomore detail in each one of them.
But the first drug class is thebiguanides or the Metformin or Glucophage.
It's been around for donkeys years.
The second group is theSGLT two inhibitors.
Whoa, wait!
Donkeys years?
Is that not an American?
No, but I like it.
(15:18):
I like that.
I'm gonna start using that term.
Donkey's years is a long time.
Okay, let's go with that.
Alright.
You can take, you can take donkey'stime to explain this if you want.
Go right ahead.
See, I'm, I'm already using that term.
The SGLT two inhibitors, which act mainlyon the kidneys and pull glucose outta
the kidneys, and then the new kids on theblock, which is the GLP-1 inhibitors that
(15:42):
everyone's kind of got on board with.
But if we go back to, so the Metformin,glucophage, it's basically, what it
does is improves insulin sensitivity.
So type two diabetes, your primary problemis that you've got insulin resistance.
And so in other words, the gates ofthose cells are not opening and they're
not allowing the glucose into the cells.
This drug is absolutely essentialfor any type two diabetic.
(16:06):
Anyone with pre-diabetes, anyonewith metabolic syndrome because
there is that basic underlyingproblem of insulin resistance.
But what we're starting to see is thisissue of double diabetes, and I wanna
flag that and then maybe just come backto it a bit later, but double diabetes
basically just refers to a dual diagnosisof type one and type two diabetes.
(16:27):
And we are starting to see a lot morepeople being diagnosed with, or a lot
of, yeah, a lot of people being diagnosedwith type one and type two, but a lot more
people who live with type one diabetes whohave some degree of insulin resistance.
Mm-hmm.
Whether it's because they have a familyhistory of diabetes, whether it's
because we have sedentary lifestyles,whether it's because our population
(16:48):
is becoming more overweight, andthat's leading to this whole issue
of insulin resistance, I'm not sure.
But Metformin becomes very useful thereand I was actually just having a look.
There was actually a, a trial that theydid called the REMOVAL trial, where they
looked at the use of metformin in typeone diabetes to reduce the, and looked at
its effect on the arterial wall lining.
(17:11):
So one of the main problems in type twodiabetes is that you get atherosclerosis,
which is a thickening and a plaqueformation on the arterial walls.
That then leads to yourstrokes and heart attacks.
And so if you can reduce thatintimal thickening, you can
very often reduce your risk.
And they looked at the use ofmetformin in order to reduce this.
It didn't reach the primary endpoint.
(17:31):
In other words, the primaryreason for what the, the, the
trial was, was set up for.
But it did have a small reductionin hbA1c, so your average glucose,
a reduction in weight, a reductionin LDL, which is one of your
cholesterol markers, and a reductionin the amount of insulin used.
And that kind of makes sense becauseyou may, um, you making the body more
insulin sensitive and it also improvedrenal functioning to a certain extent.
(17:55):
We know that metformin is avery inexpensive medication
Absolutely.
Relative to most others.
What are some of the potentialside effects of using it?
There really aren't any.
I mean, we've been using it for so long.
A lot of people used tocomplain of some gastric side,
gastrointestinal side effects.
They'll feel a bit of nausea orconstipation or diarrhea, but now
(18:16):
they have extended release forms andthat people can take at nighttime.
And quite honestly, I've got a handfulof patients that still complain about
the side effects on the XR format.
As you say, it's exceptionallycheap because it's been
around for donkeys years.
And yeah, it's really very safe.
I can think of certain populationswithin the Type one space
(18:37):
who become insulin resistant.
You know, maybe it'stemporary, maybe it's not like,
yeah.
During adolescence we see on teenagersinsulin needs skyrocket a lot of times.
Certainly people who are, who gain weight.
Anybody
who's in a family history of diabetes.
Yeah.
Of type 2 diabetes and familyhistory of cardiovascular disease.
Yeah.
And you know, if it, if it makes thebody more sensitive to insulin and,
(18:59):
and keeps the liver from overproducingglucose, it can keep blood sugars
much more stable and, uh, yourequire far less insulin to do it.
Yep.
Makes sense for morepeople to be using it.
Yep.
All right.
The second class you mentionedwere the GLP-1 receptor agonists.
That's, uh, one of themore popular meds now.
(19:21):
I read recently that in the US 6% ofthe entire population is already using
one of these drugs and it's growing,and so tell us a little more about that.
So they're a very interesting class ofdrugs because one of the main problems
with insulin a few years ago waspeople didn't like taking injections.
Now you bring GLP-1s on themarkets and no one's got a
(19:43):
problem with injections anymore.
They're all pretty happy.
And there's the rub.
Insulin will tend to lead to someweight gain, but what did the GLP-1s do?
Weight loss.
Weight loss.
Amazing what people will, will putthemselves through to lose some weight.
Absolutely.
It's amazing.
Sorry to interrupt.
Go ahead.
As you say, what the othermisconception about the GLP-1s is
(20:03):
that they suppress your appetite.
They don't suppress your appetite.
They promote satiety, and it might soundlike we're splitting hairs, but it's
quite an important difference to make.
They're not suppressing your appetite.
So you sit down for your eveningmeal and you feel nauseous and you
can't eat, and you know, you don'teat anything for the whole day.
All they're doing is they're allowingyou to differentiate between what you
(20:24):
need to eat and what you want to eat.
So as soon as you've eaten thecalories that you need to for the
day, or in a specific meal, that youthen feel satisfied and you don't
feel like you need to eat anymore.
And I've had patients describing exactlythat, that they sit down, they look at a
big chocolate cake, and they think, no,that chocolate cake looks great, but I
actually don't need to eat it right now.
(20:45):
I don't think I'll ever get there.
Even on the drug looking atchocolate and not wanting to eat it.
Yeah.
So that's the, one of theirmain mechanisms of action
that happens in the brain.
And then they promote insulin secretion,but a glucose dependent insulin secretion.
So if you're glucose, there was a
And so this is only in peoplewho can make insulin still.
So someone with type one who has no betacell function, you wouldn't see that.
(21:07):
So yeah, I mean, yeah, basically, yes.
Um, quite a lot of type ones for someor other reasons still do have a little
bit of residual beta cell function,and very often you do see that it
actually does enhance a little bit more.
But yeah, it also suppresses theglucagon, so in between meals you're
not getting that glucagon surge.
So it's really good at stoppingthose postprandial glucose
(21:29):
spikes, um, decreasing insulindoses that are required.
And then it also slowsdown your gastric emptying.
So in other words, your stomachempties itself slower, so you digest
the food better, you can absorbthe nutrients from the food better,
and you just feel full of longer.
So it really does help thosepostprandial or post-meal glucose
spikes and then obviously helpswith the weight management as well.
(21:50):
Wow.
It has a multitude of benefitspotentially for people with type
one, even if it doesn't helpmuch with the insulin production.
You know, you got slower digestion, youget a sense of fullness-- satiety, you
know, early on when you start eating.
It prevents the glucagon productionthat happens inappropriately
sometimes after we eat.
(22:11):
Uh, 'cause you know, protein intake causesglucagon production and that can make
the sugar spike even more after meals.
So it, it sounds like it could offer alot of benefits for people with type one.
Not, not to mention, you know,that over time the, the, the
gradual weight loss that occurs.
Absolutely.
What are, what are some of thedrawbacks to using a GLP-1?
(22:32):
So I think the biggest drawback is, again,a misconception that a GLP-1 is insulin
because they're both injections and I'veoften, people heard people talking about
my new insulin that they're taking.
It's completely not insulin.
And if you understand that people withtype one diabetes require insulin,
it's not a replacement for insulin.
(22:53):
So I think that's the biggestthing to just drive home and it's,
it's certainly not a replacement.
The other problem is that itcan still cause hypoglycemia if
you don't adjust the insulin.
So, because it's... so making you alittle bit more insulin sensitive and
and enhancing the insulin secretion.
Very often we find that people do needto reduce their insulin, um, doses
(23:15):
and if you're not doing that, thenyou can obviously get hypoglycemia.
Yeah.
If you get hypoglycemic andovertreat them like I do, the
weight's not gonna come off.
Absolutely.
You're still packing on the calories.
Yeah.
Yeah.
I still use my lows as a, Idon't know, an opportunity to
just devour mass quantities.
(23:35):
I gotta, I really have to work on that.
Just one more thing on the GLP-1s, Ithink, um, one of the main benefits in
type two diabetes is that they offersome cardiovascular protection in type
two diabetes, which is obviously amassive problem in type two diabetes.
Mm-hmm.
But the trials haven't yetbeen published on whether you
still get that cardiovascularprotection in type one diabetes.
(23:55):
That hasn't yet been proven.
I suppose it stands to reason that theywould, but it hasn't yet been proven.
Now, is that cardiovascular benefit,is that dependent on one losing weight
or would it happen even if somebodydidn't lose weight with those drugs?
So in type two diabetes, it'snot dependent on the weight.
It's independent of the weight lossand of the HbA1c, but that's what
(24:20):
we don't know in type one diabetes.
Okay.
It seems to reason that it would probably
absolutely
apply.
And we're human beings.
It seems like it wouldwork in both populations.
Absolutely.
Yeah.
Um, and then the third class ofdrugs are called SGLT two inhibitors.
Now, these have been outlonger, even in the GLP-1s.
And I remember when these firstcame out and I, I gave it a try.
(24:42):
It's an oral medication.
If you know-- why not?
Uh, and it brought me back to the dayswhen I was first diagnosed with diabetes
where I was just peeing my brains out'cause my sugars were high all the time.
And now all of a sudden.
Even with blood sugars thatwere in a decent range, I was
still peeing my brains out.
So tell us about the SGLT twoinhibitors and what they do.
Well, that's, that'sexactly how they work.
(25:04):
They basically just make you pee outall the glucose that you don't need.
And so they act on the kidneys.
They act on intraarterial,and they pull out all the, the
excess glucose into the kidneys.
So, immediately you can see what theproblem's going to be is that you've
now got a bladder full of glucose.
And because you're pulling out all thatglucose and from the kidneys, your, your
urine's going through into the bladder--infections, bugs, glucose, so all your
(25:27):
urinary infections, actually transmitinfections, that risk is increased if--
in someone taking an SGLT two inhibitor.
The other problem is that in typeone diabetes, we often get, well not
often, but you can get what's calleda Euglycemic Diabetic Ketoacidosis.
So in other words, you're getting aketotic state happening at a normal
(25:49):
sugar level because of the wayin which the, the drug is pulling
sugar out of the other kidneys.
And so you've gotta be really carefulof monitoring your ketones and alerting
patients who are on an SGLT two inhibitorthat they need to still think about it
at DKA, even at a normal glucose level.
Very often we say,
What are some things the user cando to prevent the ketotic state
(26:10):
when they're using these drugs?
So the main one is, is hydration.
So it's just drinking copious amountsof water and making sure that you
void the bladder on a regular basisso that you're not sitting there
with a full bladder full of sugaryurine waiting to get an infection.
To be quite honest if... I give thatinformation to all my patients, and
I've had very few having infections.
I've heard from colleagues who perhapsdon't give that same sort of information
(26:34):
out that they have a problem withpatients coming back with recurrent UTIs.
But I think it's a very simplemessage to give to patients.
And if you give the message, peopleare generally more aware of it.
I imagine that, uh, users have to beconscious to be consuming carbohydrates
as well, because if they're urinatingglucose away, you know, its taking
away from the energy their body needs.
(26:55):
So people who wanna follow lowcarb diets are probably not great
candidates for use of these.
Absolutely.
Okay.
Any other benefits that are seenwith the SGLT two inhibitors?
No.
So, I mean, there, they have showed, thereare trials that show modest improvements
in glucose, um, uh, reduction weightloss, a decreased in the insulin doses.
(27:18):
But the, the, the risk, as Isaid is that you've gotta care...
monitor it very carefully andselect your patients very carefully.
How about kidney function?
Now, one would think if it's causingthe kidneys to secrete sugar, then
it's gonna be harmful to the kidneys.
Is that the case?
So the interesting thing is youactually can take it down to quite
low levels of kidney function.
(27:38):
Um, and it's actually, uh,often benefits the kidneys,
certainly in type two diabetes.
I think, in South Africa, wecan use it to a GFR of 25.
I think internationally they've pushedit down to 20 or maybe even 15 I think.
So it is safe to use it in those.
Often, you just want to reduce thedose at those very lower levels.
But it is safe to use and it hasbenefits to the kidneys at that stage.
(28:02):
So again, it's one of those drugswhere it's not only helping the
glucose, but it's assisting yourcomplications and, and reducing the
risk of the complications that we arelooking out for in diabetes as well.
Okay.
So let's, let's take those three classesof meds and just kind of quickly summarize
the, the biguanides, specificallyMetformin and Metformin extended release.
(28:24):
Who might be a good candidatepotentially for using metformin?
So those are the ones that have gotthis double diagnosis of diabetes.
People are overweight, sedentarylifestyles, family history, and it
doesn't necessarily have to be amassive obese, massively obese person.
It can just be an overweight person.
Um, so that would be, and it'svery safe, very simple to take.
(28:46):
It's a single tabletthat you take at night.
So that would be that population.
The SGLT-2.
Before you move ahead, we, we'veactually found that patients who struggle
with irregularities in their bloodsugar overnight can sometimes benefit
because the overnight irregularitiesare due to the liver putting out
large amounts of glucose, and themetformin can suppress that and keep
(29:10):
things much more stable at night.
So that's, we found that tobe a, an effective use for it.
Yep.
SGLT twos.
I think here the key is patient selection.
You want to be really careful and you,you want a very well educated patients.
Not necessarily scholastically welleducated, but just diabetes, well
educated and very informed about theirdiabetes that you've told them about DKAs.
(29:34):
You've told them abouthydration and emptying their
bladders and things like that.
And given that it does promote someweight loss as well, since you're,
it does
urinating away glucosethroughout the day and night,
and it's got blood pressurebenefits and renal benefits as well.
Mm-hmm.
So that's the SGLT twosand then the GLP-1s.
Am I allowed to say that thatwould probably work for everybody?
(29:57):
You may.
But yeah, I mean, I really do likethe GLP-1 class of drug because
they are so multifactorial in theway that they're targeting the
glucose, uh, to hyperglycemia.
And it's happening at a brain level.
It's happening at a kidney level.
It's happening at a pancreatic level.
It's happening at a gastric level.
And yeah, so they're promoting satiety.
They're slowing gastric emptying down.
(30:19):
They're allowing you toabsorb the food better.
They're increasing insulinsecretion, uh, insulin secretion.
They're suppressing glucagon,they're suppressing those
postprandial post meal spikes.
They, um, decreasing insulindoses and promote, um,
promoting weight loss as well.
Yeah.
So we've got a lot of benef...potential benefits from these.
And, uh, you know, if you discussthem with your physician and have an
(30:39):
intelligent conversation about whyyou may wanna try one or the other.
See if your, your physicianis, is receptive to it.
They may have a specific reason thatthey may not want to prescribe it.
I would say that if they have agood medical reason for it, then
you should take their advice.
If their only reason for notprescribing it as, "well, that
would be off label." What advicewould you give somebody like that?
(31:02):
Should they probably seek out.
Another physician?
No, I think often physicians areafraid of using something off-label and
perhaps afraid of using something in a,a patient population that they're not
used to, um, and taking on that risk.
But I think if you've got the knowledgeand the information behind it and you
have a, a decent conversation with yourphysician, I don't think that too many
(31:24):
physicians these days, obviously thecost is a little bit prohibitive for some
people as well, but I don't think toomany physicians are completely against it.
Living with diabetes is scary.
We've got, besides all the extra work wehave to put into it, there's this constant
fear of serious health problems that itcan cause, as well as hypoglycemia that
(31:45):
is staring us in the face all the time.
If your physician isn't brave enoughto take a little bit of a leap of
faith that this med is gonna helpyou out of their fear for their,
their own personal, uh, wellbeing?
I don't know.
I, I, I would suggest seeing someone else.
I know your, your perspective's a littledifferent being a physician yourself.
No, I mean, I'm, I'm comfortableon prescribing it, so I don't mind.
(32:07):
It's, I think it is a lot more workfor the physician because you're
having to adjust the, the insulin alot more carefully and there's not
a lot of evidence to back you up.
But absolutely.
If the, if the patient is willingto take on some of that risk and
is well educated and happy to dothat, I don't see a problem with it.
Okay.
Well thank you.
The education is an important aspect ofall this and all, with all of our clients
(32:29):
at Integrated Diabetes, we empower them.
We, we teach them about theiroptions and not just their insulin
options or their pump options, etcetera, but we're teaching them
about their medication options.
And certainly if we, if it's somethingthat might benefit them, we'll discuss
the, the pros, the cons, and with allthree classes of drugs, you know, the
(32:50):
biguanides, the GLP-1s, and the SGLT-2s.
There are distinct advantages for peoplewith type one, but there are also some
trade-offs in terms of other healthrisks, nausea, and also potential cost.
Getting insurance to coverthem for someone with type
one isn't always possible.
Some cases it is, some cases it's not.
(33:11):
But until you try, youdon't really know for sure.
But they're certainly worth considering.
So I'd recommend everyone who's listening,if these medications are of interest
to you, if you think it's somethingyou might benefit from, talk to us.
You know, reach out to your, yourIntegrated Diabetes clinician or, you
know, do some research on your own.
And then have a... Be prepared to have anintelligent conversation, uh, with, with
(33:36):
your physician, with your prescriber.
Paula, thank you so much for takingtime out of your very busy schedule.
I know you got a lot going on withyour kids, a lot of activities.
You're on your way to, uh, to seeone of your kids in a show, right?
She's choreographed the dancing in a show.
Yep.
What show?
Alice in Wonderland.
Alice in Wonderland.
Love it.
(33:56):
That should be a lot of fun.
So let's get you on your way.
Anyway, we'll have some links aboutthis topic in the show notes if
anybody would like to check those out.
I'm Gary Scheiner reminding all ofyou to keep thinking like a pancreas.
Thanks for tuning in to ThinkLike a Pancreas, the podcast.
If you enjoy today's episode, don'tforget to like, follow, or subscribe
(34:18):
on your favorite podcast app.
Think Like a Pancreas, thepodcast is brought to you by
Integrated Diabetes Services.
Where experience meets expertise,passion meets compassion and diabetes
care is personal because we live it too.
Our team of clinicians all livingwith type one diabetes, understands
the challenges firsthand.
(34:39):
We're here to help no matterwhere you are in the world.
From glucose management, to self-carestrategies, the latest tech,
sports and exercise, weight loss,type one pregnancy and emotional
wellbeing, we've got you covered.
We offer consultations inEnglish and Spanish via phone,
video, chat, email and text.
(35:00):
Wanna learn more?
Visit integrateddiabetes.com oremail info@integrateddiabetes.com
to schedule a consultation.
On behalf of Think Likea Pancreas, the podcast.
I'm Gary Scheiner wishing you afantastic week ahead, and don't
forget to think like a pancreas.
Welcome to Think Like a Pancreas,the podcast where our goal is to keep
you informed, inspired, and a littleentertained on all things diabetes.
The information contained in thisprogram is based on the experience
and opinions of the IntegratedDiabetes Services clinical team.
Please discuss any changes to yourtreatment plan with your personal
(00:31):
healthcare provider before implementing.
Welcome everyone to ThinkLike a Pancreas--The Podcast.
I'm Gary Scheiner, owner and ClinicalDirector of Integrated Diabetes
Services and Type one now for 40 years.
I just hit my 40 year anniversary.
Proud to be your hostfor the program today.
The topic is type two diabetes medicationsfor people with Type one diabetes.
(00:55):
You think about it, you know we, we've hadinsulin now for over a hundred years and
it's still the only approved medicationfor the treatment of type one diabetes.
We do have Symlin, you know, the amylinhormone analog, but that's coming off the
market shortly 'cause no one was using it.
So we really just have insulinas treatment for-- approved
treatment for type one.
(01:16):
But when you think about it,you know, blood sugar management
is a multi hormone process.
In healthy people, there's a multitude ofdifferent hormones that are used to, uh,
keep glucose levels within a normal range.
So it really does beg the questionof why we only have one hormone
that we're using for type one care?
And keep in mind also that withoutproduction of the amylin hormone,
(01:41):
which is the case in people withtype one, it creates a significant
challenge for everybody to managetheir weight, their appetite, their
food intake, makes post-meal bloodsugars control a major challenge.
So this whole questionabout, what's the deal?
Why, why are we only usinginsulin in type one care?
And that's gonna be the topic today, andwe're gonna hear from a diabetologist
(02:04):
and, uh, also a member of the IDSclinical team whose expertise includes
the multidimensional managementof diabetes, Dr. Paulaa Diab.
So Paulaa, welcome.
I think everybody wouldlike to hear more about you.
Thank you.
Before I introduce myself, I havea feeling that I'm the first on
this podcast since you receivedyour fellowship for the ADCES.
(02:24):
And we were just chatting beforethe recording started and I said,
congratulations and, and in yournormal and assuming and humble way,
you don't think it's a big deal,but it actually is a very big deal
and it's a remarkable achievement.
So I just wanna say congratulations.
You're embarrassing me, Paulaa.
I appreciate that.
No, but it's a testimony to alifetime of dedication to diabetes
(02:46):
and it's very well deserved.
So congratulations.
So I'm as a diabetologist and a familyphysician, but I don't like to be
boxed into that little box because Ithink doctors sometimes just are well
known for writing scripts and sendingpeople on their way in 10 minutes.
And I think just like diabetes doesn'tcome in, neat little boxes, I enjoy
the creativity of finding differentsolutions for different people.
(03:07):
I think that's a bit of whatwe're gonna touch on today.
I think in order to do that, you needto understand the medication that
you're working with in order to exercisethat flexibility and that creativity.
I got my basic degree in medicine andthen I was launched into the world in the
middle of an HIV, um, pandemic and a ruralunderserved and under-resourced hospital.
So every time someone complains to me thatthe insurance won't pay and they can't
(03:28):
get access to medication, I always thinkback to those days and I think, well,
life isn't actually that bad anymore.
But yeah, then I completed my master's anda PhD and worked in the field of diabetes
for about 20 years and more recentlyin the field of obesity management.
And then about two years ago, decidedto study further and qualified as
a diabetes education specialist.
(03:48):
But I think I've learned more from the IDSteam than I ever have in the 20 years of
working in clinical medicine and diabetes.
And I think a couple of years ago if youhad asked me about this topic, I would've
said to you, no, type one and type twoare two very different diseases and
you can't mix and mash the medications.
But I think when you understand howthe drugs work and what they do,
(04:10):
that's when you can start to mix andmatch and, and be a bit more creative.
Yeah.
Paula, you, you came to us severalyears ago with an interest in
becoming a certified diabetescare and education specialist.
And yeah, it's not a, not a lot ofphysicians are interested in that and
I, I was very impressed by your passionfor the diabetes care field and you did
(04:34):
spend a lot of time with our team and, andthere was a lot of back and forth 'cause
clearly, you know, as a physician, there'sa lot we've learned from you as well.
But you should also mentionthat you're, you're a mom.
You've got, uh, how many--you've got three kids, right?
Two.
A son and a daughter.
It just seems like three sometimes'cause they've got so many
activities there're involved in.
It seems like thirty-three sometimes.
Yeah.
(04:54):
And, and you're in South Africa, so you'redoing this from quite a distance as well.
But you work with, um, our IntegratedDiabetes patients on weight management
and, keeping glucose managedduring, during that weight management
process, which is tricky, but youfind a way to balance all of that.
Yep.
Lots of balls in the air.
I'm the chief clown.
(05:16):
Yeah.
All right.
So I mentioned before thatglucose management is not
a simple matter of insulin.
You know, when the, when a healthy person,non--a person who doesn't have diabetes,
they manage their glucose through amultitude of, of hormonal balances.
Can you just kind of give us anoverview of what that involves?
Sure.
So I think when I'm explainingto my patients what I generally
(05:39):
say to them, I, I say, think ofglucose as fuel for your body.
So if you think ofputting gas in your car.
It's a similar sort of process and theaim is to keep that glucose between
about 70 and 125 milligrams per deciliter.
And you want the glucose to be insidethe cells and you want it to be stored.
So again, going back to the analogyof the car, you don't want the,
(06:00):
the gas sitting on the sidewalk.
You want it actually in the engine.
So it has to be in-- the glucosehas to be inside the cells.
So the key players that, that are involvedare the beta cells in your pancreas, which
obviously produce insulin, and that'sinvolved in the glucose uptake in storage
and in the alpha cells in the pancreas,which produce glucagon and that stimulates
glucose released from the liver.
(06:21):
The liver is kind of yourbuffer that's stores and
releases glucose as it's needed.
And then you've got your adipose tissueor your fat tissue, and then there are
various other organs, your muscles, um,and in fact also the brain that comes into
the whole mechanism, how it all works.
And basically what happens is aftera meal, the glucose gets pulled up
(06:42):
into the muscles and what's not beingused is then sent off to the liver.
Stored glycogen is synthesizedin the liver and it's stored.
And then between meals, when you're noteating, then the body can then pull that
stored form of glucose out of the liverand bring it back into usable form.
If that fasting state is prolonged, thebody is able to use amino acids, which
(07:04):
is proteins and various other substratesto, to produce glucose if necessary.
But that's topic fora whole other podcast.
And then there's other, there'sother hormones and that sort
of play a more supportive role.
Your, your increase in hormones inthe gut, and they amplify the insulin
release after meals as well asadrenaline, cortisol, growth hormone
(07:25):
that all impact onto that whole story.
You know, it's, it's kind of likethe thermostat in your house as soon
as your, the pancreas turns on thecooling system, so as your temperature
rises or as your blood sugar rises.
The pancreas turns on the, the coolingsystem, and insulin then moves the
glucose into the muscles and the fats inthe liver or to be stored or to be used.
And then when you haven't eaten for awhile, that temperature then starts to
(07:47):
drop and the pancreas then flips theswitch to glucagon and tells the liver to
release the stored glucose and to make newglucose, to keep things more comfortable.
And then there's, as I said,there's all the other gut hormones
and that, that interact to sortof balance it out a little bit.
Yeah, I often, I think about the caranalogy, the, the insulin driving the
glucose down and that's accelerating thecar, and the glucagon's like the brakes
(08:10):
to, to slow down that drop and help,you know, maybe bring it back up again.
But you mentioned, you know, there's alot of other hormones involved as well.
The amylin hormone, which is also secretedby the beta cells, helps to slow down the
appearance of sugar in the bloodstream.
Uhm, you know, it keeps foodfrom digesting too quickly.
It blunts appetite, so itplays an important role.
(08:32):
The adrenal hormones, uh, cause therelease of sugars into the bloodstream
whenever we're under any form of stress.
And that can be emotional stress, physicalstress, any kind of stress that can occur.
You know, and that's where the braingets involved, is causing the production
of those stress hormones when thesituation arises and the gut hormones,
(08:52):
which also regulate the movement offood through the digestive tract.
So the appearance of thesugars is regulated to a large
extent by other hormones.
So, you know, given that, you know,there are so many different hormones and
systems involved in blood sugar regulationand there are so many other medications
(09:12):
that can help to manage those for peoplewith type two diabetes, why are there so
few available for those with type one?
So I think it, there aremany different reasons.
I think one of the reasons is becauseof the primary difference between
type one and type two diabetes.
The primary problem in type onediabetes is that that thermostat
is not working and there's a lackof insulin being being produced.
(09:32):
And so you can't bring the glucose downand so you need to replace that insulin.
You've got an insulin deficiency andyou need to replace that insulin.
Whereas in type two, the keyproblem is that, is to do with the
sensitivity of your target organs.
And there are multiple ways toencourage these organs to either
become more sensitive or to utilizethe the glucose in a better way, or
(09:54):
to accept the glucose in a better way.
So I think that is the main reason,because of that underlying difference
in that you basically have togive insulin in type one diabetes.
I think also what plays into it hugely isthat the risk of diabetes ketoacidosis and
hypoglycemia is a lot greater in type onediabetes than it is in type two diabetes.
So you're very much focused on preventingthose highs and lows and you, there's a,
(10:18):
there's less wiggle room, should I say.
The Type one population is muchsmaller than the type two population.
Probably about a 90 10%split um, worldwide.
Now, if you're looking at doing atrial or you're looking at marketing
a drug that's gonna be cost effectiveand have a big population to take
it up, there just aren't the numberof people in Type one diabetes.
(10:39):
Yeah.
So a lot of it comes down to dollars.
Absolutely the pharmaceutical companieswanna return on their investment and it
is a huge investment to develop a drug,to test it, to submit it, to market it.
It's a huge, an investment, andthey don't always see the type one
population as large enough to help themrecoup that investment, unfortunately.
(11:02):
You know, the government'snot really helping at this
point in that regard either.
So we're counting on thefree market system to dictate
what drugs come to market.
And if there were 10 times as manytype ones as there are, yeah, there'd
probably be more, more medications, moretreatments available than what we have.
But I think having said that, the waythat we currently doing it, where we are
(11:23):
developing and marketing drugs for typetwo and then using them off-label in a
type one situation, um, we kind of do
Tell me more about that.
Off-label.
I want people tounderstand what that means.
So off-label, basically... so any drugthat's produced basically gets a package
insert attached to it that tells youhow you can use it, when you can use
it, what dosage, what the side effectsare, what the contraindications are.
(11:45):
So in other words, when you absolutelycan't use it, and which populations
you can use it with, which other, whatinteractions it's got with other drugs.
Although we doctors like to be quitecreative, we actually are bound by
those rules that come with each.
Which, and if you're using somethingoff-label, it means that you're going
outside of those boundaries that areprescribed in that package insert.
(12:06):
So what is happening at the moment ispeople are using type two, or drugs that
are developed in marketed for type twodiabetes, in the type one population.
And that's not always completely unsafe,and I'll explain, we can chat about that
a little bit later and which populationsand who you, you want to give it to.
But you do have to be careful fora number of different reasons.
(12:28):
Yeah.
So, um, off label, it, it soundslike, uh, you're, you're going against
the established guidelines that thegovernment at least has set for each drug.
Can you go to jail fordoing something like that?
How risky is it?
Generally if you explain to the patientand you document that you, you explained
(12:49):
to the patient you're using it off labeland certainly not in South Africa, I
don't think anyone's gone to jail for it.
I don't dunno about in the states.
We have a lot more lawyershere, unfortunately.
But yeah, I mean basically it is just,we, we do it quite often with pregnant
patients because you can't, it's veryrisky to run a trial in a pregnant patient
on a drug that you, you're not sure of.
(13:10):
But what tends to happen is peoplefall pregnant without really
knowing that they're not meantto be taking a specific drug.
And so by trial and error we realizeactually drug A can actually be
used fairly safely in pregnancy.
And that's kind of what's happening atthe moment with, with a lot of these
drugs being used in type one diabetes.
And if you also think about howthey work, you can sort of logically
(13:31):
deduce, okay, this one will besafe in these circumstances and I
can use that drugs fairly safely.
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three, and now back to our program.
(14:15):
So pretty much anything that's beenapproved by the FDA for any indication,
for any health state, any type ofperson, it can be also prescribed to
someone else in an off-label fashion aslong as the physician or the prescriber
explains the risks to the patientand the patient's willing to accept
(14:36):
those, and I guess that's documentedsomewhere that it more or less protects
you against, against legal action.
What are some of the more common drugs ordrug classes that are prescribed off-label
to people with type one diabetes?
Yeah, so I think at the momentthere's probably about three
different classes of drugs that we'reusing on a fairly regular basis.
(14:58):
The first one is, and I'll, I'llsort of briefly just go over each
of them and then we can go intomore detail in each one of them.
But the first drug class is thebiguanides or the Metformin or Glucophage.
It's been around for donkeys years.
The second group is theSGLT two inhibitors.
Whoa, wait!
Donkeys years?
Is that not an American?
No, but I like it.
(15:18):
I like that.
I'm gonna start using that term.
Donkey's years is a long time.
Okay, let's go with that.
Alright.
You can take, you can take donkey'stime to explain this if you want.
Go right ahead.
See, I'm, I'm already using that term.
The SGLT two inhibitors, which act mainlyon the kidneys and pull glucose outta
the kidneys, and then the new kids on theblock, which is the GLP-1 inhibitors that
(15:42):
everyone's kind of got on board with.
But if we go back to, so the Metformin,glucophage, it's basically, what it
does is improves insulin sensitivity.
So type two diabetes, your primary problemis that you've got insulin resistance.
And so in other words, the gates ofthose cells are not opening and they're
not allowing the glucose into the cells.
This drug is absolutely essentialfor any type two diabetic.
(16:06):
Anyone with pre-diabetes, anyonewith metabolic syndrome because
there is that basic underlyingproblem of insulin resistance.
But what we're starting to see is thisissue of double diabetes, and I wanna
flag that and then maybe just come backto it a bit later, but double diabetes
basically just refers to a dual diagnosisof type one and type two diabetes.
(16:27):
And we are starting to see a lot morepeople being diagnosed with, or a lot
of, yeah, a lot of people being diagnosedwith type one and type two, but a lot more
people who live with type one diabetes whohave some degree of insulin resistance.
Mm-hmm.
Whether it's because they have a familyhistory of diabetes, whether it's
because we have sedentary lifestyles,whether it's because our population
(16:48):
is becoming more overweight, andthat's leading to this whole issue
of insulin resistance, I'm not sure.
But Metformin becomes very useful thereand I was actually just having a look.
There was actually a, a trial that theydid called the REMOVAL trial, where they
looked at the use of metformin in typeone diabetes to reduce the, and looked at
its effect on the arterial wall lining.
(17:11):
So one of the main problems in type twodiabetes is that you get atherosclerosis,
which is a thickening and a plaqueformation on the arterial walls.
That then leads to yourstrokes and heart attacks.
And so if you can reduce thatintimal thickening, you can
very often reduce your risk.
And they looked at the use ofmetformin in order to reduce this.
It didn't reach the primary endpoint.
(17:31):
In other words, the primaryreason for what the, the, the
trial was, was set up for.
But it did have a small reductionin hbA1c, so your average glucose,
a reduction in weight, a reductionin LDL, which is one of your
cholesterol markers, and a reductionin the amount of insulin used.
And that kind of makes sense becauseyou may, um, you making the body more
insulin sensitive and it also improvedrenal functioning to a certain extent.
(17:55):
We know that metformin is avery inexpensive medication
Absolutely.
Relative to most others.
What are some of the potentialside effects of using it?
There really aren't any.
I mean, we've been using it for so long.
A lot of people used tocomplain of some gastric side,
gastrointestinal side effects.
They'll feel a bit of nausea orconstipation or diarrhea, but now
(18:16):
they have extended release forms andthat people can take at nighttime.
And quite honestly, I've got a handfulof patients that still complain about
the side effects on the XR format.
As you say, it's exceptionallycheap because it's been
around for donkeys years.
And yeah, it's really very safe.
I can think of certain populationswithin the Type one space
(18:37):
who become insulin resistant.
You know, maybe it'stemporary, maybe it's not like,
yeah.
During adolescence we see on teenagersinsulin needs skyrocket a lot of times.
Certainly people who are, who gain weight.
Anybody
who's in a family history of diabetes.
Yeah.
Of type 2 diabetes and familyhistory of cardiovascular disease.
Yeah.
And you know, if it, if it makes thebody more sensitive to insulin and,
(18:59):
and keeps the liver from overproducingglucose, it can keep blood sugars
much more stable and, uh, yourequire far less insulin to do it.
Yep.
Makes sense for morepeople to be using it.
Yep.
All right.
The second class you mentionedwere the GLP-1 receptor agonists.
That's, uh, one of themore popular meds now.
(19:21):
I read recently that in the US 6% ofthe entire population is already using
one of these drugs and it's growing,and so tell us a little more about that.
So they're a very interesting class ofdrugs because one of the main problems
with insulin a few years ago waspeople didn't like taking injections.
Now you bring GLP-1s on themarkets and no one's got a
(19:43):
problem with injections anymore.
They're all pretty happy.
And there's the rub.
Insulin will tend to lead to someweight gain, but what did the GLP-1s do?
Weight loss.
Weight loss.
Amazing what people will, will putthemselves through to lose some weight.
Absolutely.
It's amazing.
Sorry to interrupt.
Go ahead.
As you say, what the othermisconception about the GLP-1s is
(20:03):
that they suppress your appetite.
They don't suppress your appetite.
They promote satiety, and it might soundlike we're splitting hairs, but it's
quite an important difference to make.
They're not suppressing your appetite.
So you sit down for your eveningmeal and you feel nauseous and you
can't eat, and you know, you don'teat anything for the whole day.
All they're doing is they're allowingyou to differentiate between what you
(20:24):
need to eat and what you want to eat.
So as soon as you've eaten thecalories that you need to for the
day, or in a specific meal, that youthen feel satisfied and you don't
feel like you need to eat anymore.
And I've had patients describing exactlythat, that they sit down, they look at a
big chocolate cake, and they think, no,that chocolate cake looks great, but I
actually don't need to eat it right now.
(20:45):
I don't think I'll ever get there.
Even on the drug looking atchocolate and not wanting to eat it.
Yeah.
So that's the, one of theirmain mechanisms of action
that happens in the brain.
And then they promote insulin secretion,but a glucose dependent insulin secretion.
So if you're glucose, there was a
And so this is only in peoplewho can make insulin still.
So someone with type one who has no betacell function, you wouldn't see that.
(21:07):
So yeah, I mean, yeah, basically, yes.
Um, quite a lot of type ones for someor other reasons still do have a little
bit of residual beta cell function,and very often you do see that it
actually does enhance a little bit more.
But yeah, it also suppresses theglucagon, so in between meals you're
not getting that glucagon surge.
So it's really good at stoppingthose postprandial glucose
(21:29):
spikes, um, decreasing insulindoses that are required.
And then it also slowsdown your gastric emptying.
So in other words, your stomachempties itself slower, so you digest
the food better, you can absorbthe nutrients from the food better,
and you just feel full of longer.
So it really does help thosepostprandial or post-meal glucose
spikes and then obviously helpswith the weight management as well.
(21:50):
Wow.
It has a multitude of benefitspotentially for people with type
one, even if it doesn't helpmuch with the insulin production.
You know, you got slower digestion, youget a sense of fullness-- satiety, you
know, early on when you start eating.
It prevents the glucagon productionthat happens inappropriately
sometimes after we eat.
(22:11):
Uh, 'cause you know, protein intake causesglucagon production and that can make
the sugar spike even more after meals.
So it, it sounds like it could offer alot of benefits for people with type one.
Not, not to mention, you know,that over time the, the, the
gradual weight loss that occurs.
Absolutely.
What are, what are some of thedrawbacks to using a GLP-1?
(22:32):
So I think the biggest drawback is, again,a misconception that a GLP-1 is insulin
because they're both injections and I'veoften, people heard people talking about
my new insulin that they're taking.
It's completely not insulin.
And if you understand that people withtype one diabetes require insulin,
it's not a replacement for insulin.
(22:53):
So I think that's the biggestthing to just drive home and it's,
it's certainly not a replacement.
The other problem is that itcan still cause hypoglycemia if
you don't adjust the insulin.
So, because it's... so making you alittle bit more insulin sensitive and
and enhancing the insulin secretion.
Very often we find that people do needto reduce their insulin, um, doses
(23:15):
and if you're not doing that, thenyou can obviously get hypoglycemia.
Yeah.
If you get hypoglycemic andovertreat them like I do, the
weight's not gonna come off.
Absolutely.
You're still packing on the calories.
Yeah.
Yeah.
I still use my lows as a, Idon't know, an opportunity to
just devour mass quantities.
(23:35):
I gotta, I really have to work on that.
Just one more thing on the GLP-1s, Ithink, um, one of the main benefits in
type two diabetes is that they offersome cardiovascular protection in type
two diabetes, which is obviously amassive problem in type two diabetes.
Mm-hmm.
But the trials haven't yetbeen published on whether you
still get that cardiovascularprotection in type one diabetes.
(23:55):
That hasn't yet been proven.
I suppose it stands to reason that theywould, but it hasn't yet been proven.
Now, is that cardiovascular benefit,is that dependent on one losing weight
or would it happen even if somebodydidn't lose weight with those drugs?
So in type two diabetes, it'snot dependent on the weight.
It's independent of the weight lossand of the HbA1c, but that's what
(24:20):
we don't know in type one diabetes.
Okay.
It seems to reason that it would probably
absolutely
apply.
And we're human beings.
It seems like it wouldwork in both populations.
Absolutely.
Yeah.
Um, and then the third class ofdrugs are called SGLT two inhibitors.
Now, these have been outlonger, even in the GLP-1s.
And I remember when these firstcame out and I, I gave it a try.
(24:42):
It's an oral medication.
If you know-- why not?
Uh, and it brought me back to the dayswhen I was first diagnosed with diabetes
where I was just peeing my brains out'cause my sugars were high all the time.
And now all of a sudden.
Even with blood sugars thatwere in a decent range, I was
still peeing my brains out.
So tell us about the SGLT twoinhibitors and what they do.
Well, that's, that'sexactly how they work.
(25:04):
They basically just make you pee outall the glucose that you don't need.
And so they act on the kidneys.
They act on intraarterial,and they pull out all the, the
excess glucose into the kidneys.
So, immediately you can see what theproblem's going to be is that you've
now got a bladder full of glucose.
And because you're pulling out all thatglucose and from the kidneys, your, your
urine's going through into the bladder--infections, bugs, glucose, so all your
(25:27):
urinary infections, actually transmitinfections, that risk is increased if--
in someone taking an SGLT two inhibitor.
The other problem is that in typeone diabetes, we often get, well not
often, but you can get what's calleda Euglycemic Diabetic Ketoacidosis.
So in other words, you're getting aketotic state happening at a normal
(25:49):
sugar level because of the wayin which the, the drug is pulling
sugar out of the other kidneys.
And so you've gotta be really carefulof monitoring your ketones and alerting
patients who are on an SGLT two inhibitorthat they need to still think about it
at DKA, even at a normal glucose level.
Very often we say,
What are some things the user cando to prevent the ketotic state
(26:10):
when they're using these drugs?
So the main one is, is hydration.
So it's just drinking copious amountsof water and making sure that you
void the bladder on a regular basisso that you're not sitting there
with a full bladder full of sugaryurine waiting to get an infection.
To be quite honest if... I give thatinformation to all my patients, and
I've had very few having infections.
I've heard from colleagues who perhapsdon't give that same sort of information
(26:34):
out that they have a problem withpatients coming back with recurrent UTIs.
But I think it's a very simplemessage to give to patients.
And if you give the message, peopleare generally more aware of it.
I imagine that, uh, users have to beconscious to be consuming carbohydrates
as well, because if they're urinatingglucose away, you know, its taking
away from the energy their body needs.
(26:55):
So people who wanna follow lowcarb diets are probably not great
candidates for use of these.
Absolutely.
Okay.
Any other benefits that are seenwith the SGLT two inhibitors?
No.
So, I mean, there, they have showed, thereare trials that show modest improvements
in glucose, um, uh, reduction weightloss, a decreased in the insulin doses.
(27:18):
But the, the, the risk, as Isaid is that you've gotta care...
monitor it very carefully andselect your patients very carefully.
How about kidney function?
Now, one would think if it's causingthe kidneys to secrete sugar, then
it's gonna be harmful to the kidneys.
Is that the case?
So the interesting thing is youactually can take it down to quite
low levels of kidney function.
(27:38):
Um, and it's actually, uh,often benefits the kidneys,
certainly in type two diabetes.
I think, in South Africa, wecan use it to a GFR of 25.
I think internationally they've pushedit down to 20 or maybe even 15 I think.
So it is safe to use it in those.
Often, you just want to reduce thedose at those very lower levels.
But it is safe to use and it hasbenefits to the kidneys at that stage.
(28:02):
So again, it's one of those drugswhere it's not only helping the
glucose, but it's assisting yourcomplications and, and reducing the
risk of the complications that we arelooking out for in diabetes as well.
Okay.
So let's, let's take those three classesof meds and just kind of quickly summarize
the, the biguanides, specificallyMetformin and Metformin extended release.
(28:24):
Who might be a good candidatepotentially for using metformin?
So those are the ones that have gotthis double diagnosis of diabetes.
People are overweight, sedentarylifestyles, family history, and it
doesn't necessarily have to be amassive obese, massively obese person.
It can just be an overweight person.
Um, so that would be, and it'svery safe, very simple to take.
(28:46):
It's a single tabletthat you take at night.
So that would be that population.
The SGLT-2.
Before you move ahead, we, we'veactually found that patients who struggle
with irregularities in their bloodsugar overnight can sometimes benefit
because the overnight irregularitiesare due to the liver putting out
large amounts of glucose, and themetformin can suppress that and keep
(29:10):
things much more stable at night.
So that's, we found that tobe a, an effective use for it.
Yep.
SGLT twos.
I think here the key is patient selection.
You want to be really careful and you,you want a very well educated patients.
Not necessarily scholastically welleducated, but just diabetes, well
educated and very informed about theirdiabetes that you've told them about DKAs.
(29:34):
You've told them abouthydration and emptying their
bladders and things like that.
And given that it does promote someweight loss as well, since you're,
it does
urinating away glucosethroughout the day and night,
and it's got blood pressurebenefits and renal benefits as well.
Mm-hmm.
So that's the SGLT twosand then the GLP-1s.
Am I allowed to say that thatwould probably work for everybody?
(29:57):
You may.
But yeah, I mean, I really do likethe GLP-1 class of drug because
they are so multifactorial in theway that they're targeting the
glucose, uh, to hyperglycemia.
And it's happening at a brain level.
It's happening at a kidney level.
It's happening at a pancreatic level.
It's happening at a gastric level.
And yeah, so they're promoting satiety.
They're slowing gastric emptying down.
(30:19):
They're allowing you toabsorb the food better.
They're increasing insulinsecretion, uh, insulin secretion.
They're suppressing glucagon,they're suppressing those
postprandial post meal spikes.
They, um, decreasing insulindoses and promote, um,
promoting weight loss as well.
Yeah.
So we've got a lot of benef...potential benefits from these.
And, uh, you know, if you discussthem with your physician and have an
(30:39):
intelligent conversation about whyyou may wanna try one or the other.
See if your, your physicianis, is receptive to it.
They may have a specific reason thatthey may not want to prescribe it.
I would say that if they have agood medical reason for it, then
you should take their advice.
If their only reason for notprescribing it as, "well, that
would be off label." What advicewould you give somebody like that?
(31:02):
Should they probably seek out.
Another physician?
No, I think often physicians areafraid of using something off-label and
perhaps afraid of using something in a,a patient population that they're not
used to, um, and taking on that risk.
But I think if you've got the knowledgeand the information behind it and you
have a, a decent conversation with yourphysician, I don't think that too many
(31:24):
physicians these days, obviously thecost is a little bit prohibitive for some
people as well, but I don't think toomany physicians are completely against it.
Living with diabetes is scary.
We've got, besides all the extra work wehave to put into it, there's this constant
fear of serious health problems that itcan cause, as well as hypoglycemia that
(31:45):
is staring us in the face all the time.
If your physician isn't brave enoughto take a little bit of a leap of
faith that this med is gonna helpyou out of their fear for their,
their own personal, uh, wellbeing?
I don't know.
I, I, I would suggest seeing someone else.
I know your, your perspective's a littledifferent being a physician yourself.
No, I mean, I'm, I'm comfortableon prescribing it, so I don't mind.
(32:07):
It's, I think it is a lot more workfor the physician because you're
having to adjust the, the insulin alot more carefully and there's not
a lot of evidence to back you up.
But absolutely.
If the, if the patient is willingto take on some of that risk and
is well educated and happy to dothat, I don't see a problem with it.
Okay.
Well thank you.
The education is an important aspect ofall this and all, with all of our clients
(32:29):
at Integrated Diabetes, we empower them.
We, we teach them about theiroptions and not just their insulin
options or their pump options, etcetera, but we're teaching them
about their medication options.
And certainly if we, if it's somethingthat might benefit them, we'll discuss
the, the pros, the cons, and with allthree classes of drugs, you know, the
(32:50):
biguanides, the GLP-1s, and the SGLT-2s.
There are distinct advantages for peoplewith type one, but there are also some
trade-offs in terms of other healthrisks, nausea, and also potential cost.
Getting insurance to coverthem for someone with type
one isn't always possible.
Some cases it is, some cases it's not.
(33:11):
But until you try, youdon't really know for sure.
But they're certainly worth considering.
So I'd recommend everyone who's listening,if these medications are of interest
to you, if you think it's somethingyou might benefit from, talk to us.
You know, reach out to your, yourIntegrated Diabetes clinician or, you
know, do some research on your own.
And then have a... Be prepared to have anintelligent conversation, uh, with, with
(33:36):
your physician, with your prescriber.
Paula, thank you so much for takingtime out of your very busy schedule.
I know you got a lot going on withyour kids, a lot of activities.
You're on your way to, uh, to seeone of your kids in a show, right?
She's choreographed the dancing in a show.
Yep.
What show?
Alice in Wonderland.
Alice in Wonderland.
Love it.
(33:56):
That should be a lot of fun.
So let's get you on your way.
Anyway, we'll have some links aboutthis topic in the show notes if
anybody would like to check those out.
I'm Gary Scheiner reminding all ofyou to keep thinking like a pancreas.
Thanks for tuning in to ThinkLike a Pancreas, the podcast.
If you enjoy today's episode, don'tforget to like, follow, or subscribe
(34:18):
on your favorite podcast app.
Think Like a Pancreas, thepodcast is brought to you by
Integrated Diabetes Services.
Where experience meets expertise,passion meets compassion and diabetes
care is personal because we live it too.
Our team of clinicians all livingwith type one diabetes, understands
the challenges firsthand.
(34:39):
We're here to help no matterwhere you are in the world.
From glucose management, to self-carestrategies, the latest tech,
sports and exercise, weight loss,type one pregnancy and emotional
wellbeing, we've got you covered.
We offer consultations inEnglish and Spanish via phone,
video, chat, email and text.
(35:00):
Wanna learn more?
Visit integrateddiabetes.com oremail info@integrateddiabetes.com
to schedule a consultation.
On behalf of Think Likea Pancreas, the podcast.
I'm Gary Scheiner wishing you afantastic week ahead, and don't
forget to think like a pancreas.
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