Thread by @cardiomet_CE

Yes it's the @GoggleDocs as we continue our #takeover of the @cardiomet_CE account.

Reporting some of the things that interested us in the recent #EASD2021

Please check out our previous mini-tweetorials.

@EASDnews @EASDelearning @ADA_DiabetesPro

Thus far we have covered...

▶️ Latest data on tirzepatide (GIP/GLP-1 dual agonist)✅
▶️ "Triple G" - a new GIP/GLP-1/Glucagon agonist✅
▶️ Remission in non-obese #type2diabetes ✅

Next up is "what's next after metformin?" - what the GRADE & TriMaster Studies add

Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE)

📍Presented an update at the #EASD2021 , although little changed from the #ADA2021 presentation.

Please check out one of our own @GoggleDocs posts at the time

https://twitter.com/drpatrickholmes/status/1409832240473858052?s=20

📍So in summary GRADE showed
1) GLP-1ra. 🥇 - ⤵️HbA1c, 🥇 - ⤵️ Any CVD events
2) Insulin. 🥇 - ⤵️ HbA1c
3) SU - most hypos
4) DPP4i- earliest to need additional glucose lowering treatments
5) TZD & SGLT2i not tested!

.... Let's now move onto the TriMaster Study

TriMaster Trial

📍Study design paper👉tinyurl.com/TriMaster

📍 Testing two hypothesis (after metformin+/-SU)
▶️1) BMI modifies TZD Rx response
▶️2) eGFR modifies SGLT2i Rx response

📍both compared to a DPP4i

📍3-way crossover study design

Outcomes

📍Primary Outcome - Diff in HbA1c between strata at 12/52

📍Secondary outcomes - for each Hypothesis
✅Tolerability
✅Weight
✅Hypoglycaemia

📍Secondary outcomes - Overall
✅Patient preference for the 3 drugs

Baseline Characteristics

🇬🇧 study

📍♂️73%

📍👴🏻94% (3% 'Asian')

📍mean BMI=31.7

📍mean eGFR=89.7

📍mean HbA1c=69

💊 Chosen
DPP4i=sitagliptin
SGLT2i=canagliflozin
TZD=pioglitazone

Results of HbA1c change

▶️Hypothesis 1
✅if BMI >30 - TZD > DPP4i at ⤵️HbA1c
✅if BMI <30 - DPP4i > TZD at ⤵️HbA1c

▶️Hypothesis 2
✅if eGFR>90 - SGLT2i > DPP4i at ⤵️HbA1c
✅if eGFR 60-90 - DPP4i > SGLT2i at ⤵️HbA1c

⚠️small difference approx 3 mmol/mol (0.25%) between groups

Secondary outcomes

📍Between groups the only statistically difference was TZD ⤴️wt if BMI>30

📍Overall

No difference in HbA1c change between drugs

✅TZD best tolerated by participants (p=0.052)

✅DPP4i least side-effects reported

✅SGLT2i best at weight

📍All 💊 were prefered by some!

📍overall SGLT2i>DPP4i>TZD

📍TZD
🙁wt gain
🙁change in appetite
🙁hypos

📍DPP4i
🤢feeling sick

📍SGLT2i
🙁passing more urine
🙁Thirst
🙁Feeling dehydrated
🙁Thrush
🤔Rashes

Bottomline on patient preference

It appears to be the number of side-effects experienced, rather than weight ⤴️ ⤵️ or HbA1c⤵️ that impacts on patient preference.

So what next after metformin?

📍No simple one size fits all it depends on
▶️ What 💊/💉 the patient can tolerate
▶️ Patient factors (e.g. frailty, eGFR, weight)
▶️ co-morbidities (e.g. eASCVD, Heart Failure, CKD)

📍HCP:Patient communication
&
📍Shared-decision making are key!

And finally (for now)....

I think the ADA/EASD nailed this one back in 2018 👉rdcu.be/8JZn

Although studies like GRADE & TriMaster add granularity into the picture

... keep tuned to @cardiomet_ce as we will be back with SOON with more from the @GoggleDocs