Thread by @cardiomet_CE

Welcome to our final Goggledocs tweetorial from this #EASD2021 takeover!
Over the last few days we have discussed all things cardio-reno-metabolic including SGLT2s, GLP1s, dual agonists, triple agonists….but not mentioned much about type 1 diabetes…

So today we are going to end on a cardiometabolic focused look at Type 1 Diabetes with data from #EASD2021 interwoven in... stay tuned!

One of the key sessions and guidance from @EASDnews #EASD2021 was the formalized joint ADA-EASD consesnsus report for management of type 1 diabetes… care.diabetesjournals.org/content/early/…

We have seen the impact of the ADA-EASD consensus on the management of #T2DM - so high expectations for #T1DM

The new guidelines cover a number of areas
➡️diagnosis
➡️schedule of care
➡️glucose monitoring
➡️therapy options including transplantation
➡️hypoglycaemia
➡️DKA and
... 🌟considerations for adjunctive therapy – an area we will focus on today...

But before that, an interesting look at diagnosing type 1 diabetes….

It might seem straightforward...test for auto-antibodies and if ➕ve ….there’s your diagnosis…

However….
We know the diagnosis is not always so clear cut, especially in
➡️older age groups
➡️➖ve antibodies

This suggests using age as an initial decision point and then considering options including genetic testing. Highlighting the importance of c-peptide testing to help support diagnosis…and management!

We are interested to know…do you routinely use/consider C-peptide testing in your patients? @EASDnews @EASDelearning @AmDiabetesAssn @SDelprato

Another key point is to remember that Hba1c is affected by a variety of factors not just glycaemia!
Interesting to see anaemia can ⬆️ apparent Hba1c but renal failure (which also can cause anaemia) ⬇️apparent Hba1c

But getting back to our @cardiomet_CE focus…
The guideline also discusses adjunctive therapies in those with #T1DM..

#EASD2021

Let’s look at metformin….

It’s use in T2DM is well known and accepted… but what about in T1DM and specifically - any evidence of CV benefit…

This is indeed the elephant in the room – CVOTs with SGLT2s and GLP-1s have clear evidence in T2DM but we know those with T1DM are also at risk of CV events…

care.diabetesjournals.org/content/37/10/… - worth a read!

So, with metformin, the main trial looking at this was called REMOVAL - Cardiovascular and metabolic effects of metformin in patients with type 1 diabetes
thelancet.com/journals/landi…

Aimed to investigate if metformin treatment (added to titrated insulin therapy) reduced atherosclerosis
➡️ measured by progression of common carotid artery intima-media thickness (cIMT)
➡️in adults with T1DM at increased risk CVD

✔️Adults aged 40 years and older
✔️type 1 diabetes of at least 5 years' duration
✔️at least three of ten specific cardiovascular risk factors
➡️ oral metformin 1000 mg twice daily vs placebo

1⃣ry outcome: mean far-wall cIMT (carotid intimal thickness)
2⃣ry outcomes:
➖ HbA1c
➖LDL cholesterol
➖estimated glomerular filtration rate (eGFR)
➖incident microalbuminuria and retinopathy, ➖bodyweight
➖insulin dose
➖endothelial function

➡️Progression of mean cIMT was not significantly reduced with metformin (−0·005 mm per year, 95% CI −0·012 to 0·002; p=0·1664)
➡️Maximal cIMT (a prespecified tertiary outcome) was significantly reduced (−0·013 mm per year, −0·024 to −0·003; p=0·0093)

Relevant?🤔

Small impact on
➡️Hba1c (-0.13%, seen mostly within first 3 months)
➡️Body weight (-1.17kg)
➡️LDL-c (-0.13mmol/l)
❌No real difference in insulin requirements.

Findings did not support use of metformin to improve glycaemic control in adults with T1DM….but what about the cardiovascular aspect…does maximal cIMT impact suggest some benefit even if mean cIMT unchanged? @DLBHATTMD @mvaduganathan @SABOURETCardio @ErinMichos @DrMarthaGulati

Well, ADA-EASD were not convinced and so metformin was not recommended from cardiovascular benefit perspective...or even a glucose lowering perspective either - though maybe some benefit in those with Polycystic Ovarian Syndrome

But what about the GLP-1s and SGLT2s?

.... we will get to that soon.... stay tuned!

Interesting to see GLP-1s - though not recommended from glucose lowering perspective, are considered in those with risk of CVD or renal disease….

As of now, there is no real data in those with T1DM from a CV outcome perspective…

There is some data on use in those with T1DM...
care.diabetesjournals.org/content/early/…

➡️52-week trial
➡️1,398 adults randomized
➡️3:1 to receive once-daily subcutaneous injections of liraglutide (1.8, 1.2, or 0.6 mg) or placebo added to insulin

The ADJUNCT ONE trial showed reductions in hba1c, mean body weight and reduction in insulin doses

With more participants achieving Hba1c <7% (53mmol/mol) with liraglutide 1.8mg

But...
⬆️ risk hypoglycaemia
⬆️ hyperglycaemia with ketosis

These finings were matched by ADJUNCT TWO care.diabetesjournals.org/content/39/10/…

Still not enough for a recommendation from the ADA-EASD guideline for Hb1ac but... there is potential for weight reduction...

Evidence of GLP-1 RAs in those without diabetes from SCALE (liraglutide 3mg/saxenda)...
nejm.org/doi/full/10.10…

And we have already covered semaglutide in overweight or obesity (STEP trials) previously ⬇️🙂

https://twitter.com/cardiomet_CE/status/1412750801399955457?s=20

Therefore suggesting that despite the lack of clear evidence, there might be a role for GLP-1RAs in overweight or obesity

Finally, what about SGLT2is?

The main concern is the risk of diabetic ketoacidosis (DKA) care.diabetesjournals.org/content/42/6/9…

TANDEM (Sotagliflozin), DEPICT (Dapagliflozin) and EASE (Empagliflozin) have all shown increased risk of DKA in their trials in people with T1DM

However whilst this DKA risk means they are not recommended by the FDA - this has not stopped some organisations from recommending based on the potential benefit of weight Hba1c reduction...both the EU and UK (NICE) have recommended SGLT2s as adjuncts in T1DM

Dapagliflozin is recommended as an adjunct in T1DM by @NICEComms if patients have
➡️BMI >/= 27
➡️Education programme including on DKA
➡️On at least 0.5units/kg/day of insulin
➡️Hba1c lowering of 3mmol/mol

nice.org.uk/guidance/ta597…

But what of this consideration by ADA/EASD for those with T1DM at risk of CV and renal disease?

Similarly to GLP-1s, no specific data on CV outcomes in those with T1DM...

There has even been a detailed consensus on reducing risk of DKA in those with T1DM on SGLT2s
care.diabetesjournals.org/content/42/6/1…

Though, there has been some data with post-hoc analysis of renal outcomes from the DEPICT trial (dapagliflozin) thelancet.com/journals/landi…

⬇️13.3% uACR with dapagliflozin 5mg
⬇️31.1% uACR with dapagliflozin 10mg
↔️ eGFR however

Suggesting potential for some renal benefit....but no hard outcomes as of yet

Which leads us back to #EASD2021 and this interesting risk calculator from @Stenodiabetes

Created to assess the risk of CVD or ESKD in those with T1DM
steno.shinyapps.io/T1RiskEngine/

Utilising the risk calculator, the team were able to calculate the potential risk reduction of SGLT2i usage on CV and renal disease

SGLT2i induced change in the risk variables translated into
5-year CVD ⬇️relative risk 6.1% (up to 11.1% in those with albuminuria)
5-year risk of ESKD ⬇️relative risk 5.3% (up to 7.6% in those with albuminuria)

Suggesting that this risk engine might be useful in aiding decisions on whether to start SGLT2s in those with T1DM when balancing the risks 🏅

All this highlights the need for further evidence and trials looking at cardiovascular outcomes in those with T1DM whilst not increasing adverse events...

Perhaps (as we discuss in @GoggleDocs HQ) this might be a future consideration for Finerenone given the data we see from FIDELIO and FIGARO and low DKA risk...

So to end this tweetorial with a question to check you were paying attention...
According to ADA-EASD guidelines, what C-peptide level suggests a preserved beta cell function hence suggesting type 2 diabetes diagnosis?

So there we are! 4 days of key take homes and education from #EASD2021 covering a broad range of topics, we hope to have got you thinking! This is @GoggleDocs - @drkevinfernando @AmarPut @drpatrickholmes @dr_amritlamba signing off...for now!

And that's it . . . the reins have been passed back to the home team @cardiomet_CE, who in recognition of all the expert education provided over the past four days by our friends @GoggleDocs, can now provide you with ONE HOUR CE/#CME CREDIT.

This is a first for us--an entire 1.0 CE/#CME via #tweetorials. Claim your credit 🇺🇸🇨🇦🇬🇧🇪🇺 #physicians #nurses #pharmacists at cardiometabolic-ce.com/cardiorenal11 and follow us for more programs! @MedTweetorials #cardiotwitter #FOAMed @EASDnews #meded #nephtwitter #MedTwitter @CardioNerds