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Just to remind you guys
— cardio-met (@cardiomet_CE) October 4, 2021
The @GoggleDocs are a bunch of 🇬🇧 docs/🤓 who are fascinated about the cardio-metabolic conditions we are increasingly managing.
Please check out our @YouTube channelhttps://t.co/7eCvDl8Uu3 pic.twitter.com/bKD3Ja7Uli
Up first a bit of our own “Back to the Future”!
— cardio-met (@cardiomet_CE) October 4, 2021
At the #EASD2021 conference we learned more about the exciting new Dual (GIP/GLP-1) increatin agonist #tirzepatide
After this we will briefly cover the latest data coming from @LillyPad incretin lab LY343943 aka “Triple G” pic.twitter.com/8ywDPY2f8M
Up first a bit of our own “Back to the Future”!
— cardio-met (@cardiomet_CE) October 4, 2021
At the #EASD2021 conference we learned more about the exciting new Dual (GIP/GLP-1) increatin agonist #tirzepatide
After this we will briefly cover the latest data coming from @LillyPad incretin lab LY343943 aka “Triple G” pic.twitter.com/8ywDPY2f8M
SURPASS-3 MRI trial (1/3)
— cardio-met (@cardiomet_CE) October 4, 2021
📍sub-study of SURPASS-3 (n=296)
📍1ry objective – change liver fat change at 52w
📍2ry objective – volume abdominal visceral & sub-cut. abdominal fat volume, and change from baseline pic.twitter.com/M89IZoAsIj
SURPASS-3 MRI trial (3/3)
— cardio-met (@cardiomet_CE) October 4, 2021
📍tirzepatide (particularly 10-15mg doses) looks to be possible treatments for #NAFLD #NASH, as well as #type2diabetes
📍ongoing liver outcome RCT with liver biopsy
👉https://t.co/4FBjYdZMkR pic.twitter.com/Ej0PCrHjfS
SURPASS – CGM (2/2)
— cardio-met (@cardiomet_CE) October 4, 2021
tirzepatide treatment assoc with:
📍 Marked ⤴️ in Tight TIR compared to ins. degludec at 24w & 52w ✅
📍⤴️ standard TIR ✅
In addition to
⤵️ HbA1c
⤵️⤵️ wt
⤵️ time in hyperglycaemia range
⤵️ time in hypoglycaemia range
‼️Basically it does a fabulous job pic.twitter.com/nFLh5JzQGi
SURPASS-4 (2/5)
— cardio-met (@cardiomet_CE) October 4, 2021
tirzepatide (5-15mg) vs insulin glargine assoc with …
📍HbA1c ⤵️ 8.8-12.5 mmol/mol
📍wt ⤵️ 9.0-13.5 kg
📍66% on 15mg dose >10% wt loss❗️
📍37% on 15mg dose >15% wt loss ‼️ pic.twitter.com/p3Uw6ZDK2K
SURPASS-4 (4/5)
— cardio-met (@cardiomet_CE) October 4, 2021
Tolerability & safety of tirzpatide
📍Similar GI side-effects to GLP-1ra (i.e.🤢🤮💩)
📍Numerically fewer 4-point MACE events particularly after 52w 👍 pic.twitter.com/3K6m0cu5Tr
“Triple G” (1/4) pic.twitter.com/aWnwPH9jj9
— cardio-met (@cardiomet_CE) October 4, 2021
“Triple G” (3/4)
— cardio-met (@cardiomet_CE) October 4, 2021
📍🐭 study
✅ “Triple G” beats tirzepatide‼️ (well at least in 🐁)
⤵️ wt
⤴️ insulin secretion
⤴️ insulin sensitivity
⤵️ Liver fat content
👏👏👏 pic.twitter.com/MKOGj0ncST
Keep checking the @cardiomet_CE account for more from #EASD2021
— cardio-met (@cardiomet_CE) October 4, 2021
The @GoggleDocs never stop and it won’t be long before we are posting away as part of our #TAKEOVER of this account.
Next up will be away from drugs to food… pic.twitter.com/OIvZi5yPWE
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First up led by Prof. Roy Taylor of @UniofNewcastle in collaboration with the @UniofOxford Diabetes Trial Unit.
— cardio-met (@cardiomet_CE) October 5, 2021
You may remember Prof. Taylor from the seminal DiRECT Study 👉https://t.co/t5fcaPXsBW
Today I will be going through some of the preliminary data from the ReTune Study pic.twitter.com/keJoGidlHE
What is the ReTUNE Study?
— cardio-met (@cardiomet_CE) October 5, 2021
📍Similar to DiRECT except in non-obese (BMI<27) people with #type2diabetes
📍DM duration < 7 years
📍Similar intervention as DiRECT (i.e. at least 2 weeks of 800 Kcal/day meal replacement)
📍funded by @DUK_research 🙏
👉https://t.co/ThfLDgwn04
What does this mean?
— cardio-met (@cardiomet_CE) October 5, 2021
📍 Wt. ⤵️ of 10-15kg early in #type2diabetes REGARDLESS of BMI can lead to remission‼️
📍 Extends the hope of remission to people with lower BMI
📍Challenges our traditional view of #obesity
📍 Time to define #obesity on complications rather than BMI⁉️ pic.twitter.com/0Y19fyKmDW
📍Results
— cardio-met (@cardiomet_CE) October 5, 2021
⤵️ Post-prandial glucose by 22% (2h), 18% (3h)
⤵️ GLP-1 by 66%
⤵️ Insulin first phase by 61%
⚠️larger/longer studies planned
😒 not vegan friendly
Keep checking back to the @cardiomet_CE account as we have only just scratched the surface of the #EASD2021
— cardio-met (@cardiomet_CE) October 5, 2021
Later today we will be asking the Qusetion “what next after metformin?” in the drug management of #type2diabetes reflections from Grade to TriMaster. pic.twitter.com/SnlLsYqFUT
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Thus far we have covered…
— cardio-met (@cardiomet_CE) October 6, 2021
▶️ 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 pic.twitter.com/x485fCzXxe
📍So in summary GRADE showed
— cardio-met (@cardiomet_CE) October 6, 2021
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
Outcomes
— cardio-met (@cardiomet_CE) October 6, 2021
📍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 pic.twitter.com/URJlh2uIWl
Results of HbA1c change
— cardio-met (@cardiomet_CE) October 6, 2021
▶️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 pic.twitter.com/k1Kao2qdoA
📍All 💊 were prefered by some!
— cardio-met (@cardiomet_CE) October 6, 2021
📍overall SGLT2i>DPP4i>TZD
📍TZD
🙁wt gain
🙁change in appetite
🙁hypos
📍DPP4i
🤢feeling sick
📍SGLT2i
🙁passing more urine
🙁Thirst
🙁Feeling dehydrated
🙁Thrush
🤔Rashes pic.twitter.com/qBSGUxerrX
So what next after metformin?
— cardio-met (@cardiomet_CE) October 6, 2021
📍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! pic.twitter.com/JD7bKHtbj9
And finally (for now)….
— cardio-met (@cardiomet_CE) October 6, 2021
I think the ADA/EASD nailed this one back in 2018 👉https://t.co/UdLwxQVscG
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 pic.twitter.com/vTXARcrCl9
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Yesterday we had key messages from ReTune & diabetes remission & TriMASTER exploring “what next after metformin?”
— cardio-met (@cardiomet_CE) October 6, 2021
Today @goggledocs will take you through some SGLT2 inhibitor highlights from #EASD2021 – the gift that keeps on giving! pic.twitter.com/vr1QsbPioi
Phlorizin was first isolated from bark of apple tree in 1835
— cardio-met (@cardiomet_CE) October 6, 2021
Oral ingestion of phlorizin was observed to cause glycosuria & weight loss
Phlorizin was found to be a competitive inhibitor of SGLT1 & SGLT2
SGLT2i’s are more selective synthetic analogues of phlorizin pic.twitter.com/YtlclfNjUg
A small real-world study presented at #EASD2021 looked at effects of SGLT2i’s in 450 adults ≥70 years with T2D
— cardio-met (@cardiomet_CE) October 6, 2021
✅Significant reduction in average HbA1c 7.7%>7.4% at 1y
✅Only 65 participants (14.4%) discontinued SGLT2i rx after 1y mainly driven by GU tract infections pic.twitter.com/gBOFDgfJcG
Conclusion was that SGLT2i is a valid therapeutic option in older people but caution suggested in those who are frail with guarded life expectancy
— cardio-met (@cardiomet_CE) October 6, 2021
EMPA-ELDERLY is currently recruiting (@drpatrickholmes ?!) & is 1st RCT to assess effects of SGLT2i (empagliflozin) in older people pic.twitter.com/IUakLUalUB
Ultimately we need to make a joint & informed decision with our older patients living with T2D about the risk/benefit ratio depending on their medical, functional & nutritional status, co-morbidities, support network and personal outlook on life pic.twitter.com/2O5Dx4ocBv
— cardio-met (@cardiomet_CE) October 6, 2021
Allopurinol & febuxostat reduce the risk of gout attacks; however, a recent RCT demonstrated an association between febuxostat & ⬆️CVD & all-cause mortality compared with allopurinol
— cardio-met (@cardiomet_CE) October 6, 2021
People living with T2D are at increased risk of gout & CVD
This posthoc analysis of EMPAREG OUTCOME study explored the impact of empagliflozin on new-onset gout& anti-gout meds in T2D
— cardio-met (@cardiomet_CE) October 6, 2021
✅Empa ⬇️serum uric acid by 37%
✅Empa ⬇️time to new-onset gout or antigout meds by 33%
SGLT2i may be ideal rx for gout as ⬇️risk of gout & CVD! pic.twitter.com/qOVxu9Gu0J
Worringly, NAFLD accounts for 8.4% of liover transplantations annually in Europe
— cardio-met (@cardiomet_CE) October 6, 2021
There is a bidirectional relationship with features of the metabolic syndrome and NAFLD
The presence of T2D increases the risk of cirrhosis, AF, MI, ischameic stroke & CV mortality pic.twitter.com/AhiH4TOmRL
@ABCDiab audit programme has suggested SGLT2i use associated with sig ⬇️ in ALT levels & we know ALT correlates with liver inflammation
— cardio-met (@cardiomet_CE) October 6, 2021
Other trials have demonstrated improvements in transient elastography (e.g. Fibroscan) & LFTs with dapa pic.twitter.com/LkqZPToLqE
#EASD2021 tirzepatide found to reduce liver fat by nearly half in SURPASS-3 MRI trial with associated improvements in ALT & AST
— cardio-met (@cardiomet_CE) October 6, 2021
However histopathological improvements in NASH were not assessed
Currently @NICEComms recommend pioglitazone & vitamin E regardless of diabetes status pic.twitter.com/ZPEPoHZHiD
Dapaglifozin reduced albuminuria by 29% compared with placebo
— cardio-met (@cardiomet_CE) October 6, 2021
This effect was observedd to be greater in those living with T2D pic.twitter.com/ws7iMITgl4
The benefit of dapagliflozin in DAPA-CKD on the primary composite endpoint was consistent across a range of HbA1c levels pic.twitter.com/tglHAK2lTs
— cardio-met (@cardiomet_CE) October 6, 2021
Dapagliflozin ⬇️ new onset diabetes by 33% in addition to its cardiorenal benefits
— cardio-met (@cardiomet_CE) October 6, 2021
This might appear entirely predictable given SGLT2i’s are antidiabetic drugs…
But there were no significant hba1c differences between placebo & dapa groups suggesting a possible direct effect pic.twitter.com/MAPavLMvAe
SGLT2i’s remind me of the below quote from Sir William Osler (whom i believe went to medical school with @drpatrickholmes …)
— cardio-met (@cardiomet_CE) October 6, 2021
Over my 21-year medical career to date SGLT2i’s are the most compelling therapeutic option spanning a number of comorbidities available to me in PC pic.twitter.com/d7eY0gRZbf
And it’s a wrap for today folks! Join us tomorrow for our last day of #EASD2021 key take-home messages from @GoggleDocs @cardiomet_CE takeover! @drkevinfernando @drpatrickholmes @dr_amritlamba
— cardio-met (@cardiomet_CE) October 6, 2021
Check out our YouTube channel https://t.co/4vZO59FPBB
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So today we are going to end on a cardiometabolic focused look at Type 1 Diabetes with data from #EASD2021 interwoven in… stay tuned! pic.twitter.com/4F4KE6sYCl
— cardio-met (@cardiomet_CE) October 7, 2021
We have seen the impact of the ADA-EASD consensus on the management of #T2DM – so high expectations for #T1DM pic.twitter.com/CpmjRf4mtQ
— cardio-met (@cardiomet_CE) October 7, 2021
But before that, an interesting look at diagnosing type 1 diabetes…. pic.twitter.com/gp6ZP8GxdJ
— cardio-met (@cardiomet_CE) October 7, 2021
However….
— cardio-met (@cardiomet_CE) October 7, 2021
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!
— cardio-met (@cardiomet_CE) October 7, 2021
Another key point is to remember that Hba1c is affected by a variety of factors not just glycaemia!
— cardio-met (@cardiomet_CE) October 7, 2021
Interesting to see anaemia can ⬆️ apparent Hba1c but renal failure (which also can cause anaemia) ⬇️apparent Hba1c pic.twitter.com/BJ7SOR2CV2
#EASD2021 pic.twitter.com/xbXK5MIxG5
— cardio-met (@cardiomet_CE) October 7, 2021
It’s use in T2DM is well known and accepted… but what about in T1DM and specifically – any evidence of CV benefit…
— cardio-met (@cardiomet_CE) October 7, 2021
https://t.co/UuUFUMFaAR – worth a read! pic.twitter.com/vMHn2thFSR
— cardio-met (@cardiomet_CE) October 7, 2021
Aimed to investigate if metformin treatment (added to titrated insulin therapy) reduced atherosclerosis
— cardio-met (@cardiomet_CE) October 7, 2021
➡️ measured by progression of common carotid artery intima-media thickness (cIMT)
➡️in adults with T1DM at increased risk CVD
1⃣ry outcome: mean far-wall cIMT (carotid intimal thickness)
— cardio-met (@cardiomet_CE) October 7, 2021
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)
— cardio-met (@cardiomet_CE) October 7, 2021
➡️Maximal cIMT (a prespecified tertiary outcome) was significantly reduced (−0·013 mm per year, −0·024 to −0·003; p=0·0093)
Relevant?🤔 pic.twitter.com/3WOthUwimi
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
— cardio-met (@cardiomet_CE) October 7, 2021
But what about the GLP-1s and SGLT2s?
— cardio-met (@cardiomet_CE) October 7, 2021
…. we will get to that soon…. stay tuned! pic.twitter.com/35dDoXBBVH
As of now, there is no real data in those with T1DM from a CV outcome perspective… pic.twitter.com/10DHU59qj3
— cardio-met (@cardiomet_CE) October 7, 2021
➡️52-week trial
— cardio-met (@cardiomet_CE) October 7, 2021
➡️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
With more participants achieving Hba1c <7% (53mmol/mol) with liraglutide 1.8mg pic.twitter.com/wlu0tnHgQQ
— cardio-met (@cardiomet_CE) October 7, 2021
But…
— cardio-met (@cardiomet_CE) October 7, 2021
⬆️ risk hypoglycaemia
⬆️ hyperglycaemia with ketosis
Still not enough for a recommendation from the ADA-EASD guideline for Hb1ac but… there is potential for weight reduction…
— cardio-met (@cardiomet_CE) October 7, 2021
And we have already covered semaglutide in overweight or obesity (STEP trials) previously ⬇️🙂https://t.co/cQZmeQEzWN
— cardio-met (@cardiomet_CE) October 7, 2021
Finally, what about SGLT2is? pic.twitter.com/qgPGGZOQa6
— cardio-met (@cardiomet_CE) October 7, 2021
TANDEM (Sotagliflozin), DEPICT (Dapagliflozin) and EASE (Empagliflozin) have all shown increased risk of DKA in their trials in people with T1DM pic.twitter.com/ZATbE7WK8y
— cardio-met (@cardiomet_CE) October 7, 2021
Dapagliflozin is recommended as an adjunct in T1DM by @NICEComms if patients have
— cardio-met (@cardiomet_CE) October 7, 2021
➡️BMI >/= 27
➡️Education programme including on DKA
➡️On at least 0.5units/kg/day of insulin
➡️Hba1c lowering of 3mmol/molhttps://t.co/z1wgjonRGt
Similarly to GLP-1s, no specific data on CV outcomes in those with T1DM… pic.twitter.com/mqejCMpXHg
— cardio-met (@cardiomet_CE) October 7, 2021
⬇️13.3% uACR with dapagliflozin 5mg
— cardio-met (@cardiomet_CE) October 7, 2021
⬇️31.1% uACR with dapagliflozin 10mg
↔️ eGFR however
Suggesting potential for some renal benefit….but no hard outcomes as of yet
Created to assess the risk of CVD or ESKD in those with T1DM https://t.co/WSU1UsBc9p
— cardio-met (@cardiomet_CE) October 7, 2021
SGLT2i induced change in the risk variables translated into
— cardio-met (@cardiomet_CE) October 7, 2021
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) pic.twitter.com/JOoq3W3cUv
All this highlights the need for further evidence and trials looking at cardiovascular outcomes in those with T1DM whilst not increasing adverse events…
— cardio-met (@cardiomet_CE) October 7, 2021
So to end this tweetorial with a question to check you were paying attention…
— cardio-met (@cardiomet_CE) October 7, 2021
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!
— cardio-met (@cardiomet_CE) October 7, 2021