Thread by @cardiomet_CE

It's Monday and time for us @GoggleDocs to #takeover the @cardiomet_CE account for the next few days.

It's time to revisit the recent #EASD2021 conference.

Highlights in what's new in
#T1D
#type2diabetes
#NAFLD
#CKD
#HeartFailure

Just to remind you guys

The @GoggleDocs are a bunch of 🇬🇧 docs/🤓 who are fascinated about the cardio-metabolic conditions we are increasingly managing.

Please check out our @YouTube channel
youtube.com/channel/UC8Tzu…

This accredited educational program is intended for healthcare providers only, and is supported by grants from AstraZeneca, Bayer, Chiesi, and NovoNordisk. Follow this thread for a link to credit. CE/#CME credit for #physicians, #nurses, #pharmacists in US, Canada, GB, EU.

Up first a bit of our own "Back to the Future"!

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"

#tirzepatide an investigational molecule with impressive published phase 3 data

new at #EASD2021 3 x RCT
1⃣ SURPASS-3 MRI - Looking at Liver/abdominal fat etc...
2⃣SURPASS-3 CGM - looking at time in range
3⃣SURPASS - 5 - tirzepatide vs ins. glargine in High CV risk participants

For a reminder of this molecule and the benefits in terms of ⤵️ HbA1c and ⤵️weight even when compared with current 🥇 in class therapies like semaglutide 1mg check ou the following thread.
👇

https://twitter.com/cardiomet_CE/status/1413600236577099782?s=20

A reminder of the SURPASS-3 trial

📍52w open-label phase 3 RCT
📍Insulin naive #type2diabetes
📍QW tirzepatide 5, 10 & 15mg vs insulin degludec
📍Tirzepatide compared to ins. degludec assoc with:
▶️HbA1c⤵️ 0.59-1.03%
▶️wt⤵️ 9.8-15.2 kg

full paper 👉tinyurl.com/SURPASS3

SURPASS-3 MRI trial (1/3)

📍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

SURPASS-3 MRI trial (2/3)

📍treatment with tirzepatide 5-15mg compared to ins. degludec assoc with:

🌟Liver fat content (LFC)⤵️ 18-28%
Both ⤵️ in either HbA1c or weight assoc with ⤵️

✅ Both the visceral & subcutaneous abdominal fat ⤵️ equally

✅ ALT⤵️ 4-22%
✅ AST⤵️ 10-19%

SURPASS-3 MRI trial (3/3)

📍tirzepatide (particularly 10-15mg doses) looks to be possible treatments for #NAFLD #NASH, as well as #type2diabetes

📍ongoing liver outcome RCT with liver biopsy
👉clinicaltrials.gov/ct2/show/NCT04…

SURPASS-3 CGM (1/2)

📍 another sub-study of SURPASS-3 (n=243)

📍Dexcom G6 CGM used

📍1ry outcome - Time within Tight Target range 3.9-7.8 mmol/mol (71-140 mg/dL) at 24 + 52w

📍% time within standard target range 3.9-10 mmol/mol (71-180 mg/dL) at 52w

Presented by @TBattelino

SURPASS - CGM (2/2)

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

SURPASS-4 (1/5)

⚠️One concerns 1 from SURPASS-2 was a small excess in mortality seen in the tirzepatide arm vs the semaglutide arm.

📍52w open-label RCT
📍high CV risk #type2diabetes
📍tirzepatide 5-15mg) vs insulin glargine

📍study pop
63 yr
♀️ 37%
👴🏻81.8%
Hx CV dis 86%

SURPASS-4 (2/5)

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 ‼️

SURPASS-4 (3/5)

Tirzepatide treatment assoc with...

⤵️ Systolic BP
⤵️Diastolic BP

⤴️ HDL
⤵️ TG
⤵️ Tot Cholesterol

⤴️ Heart rate

⤴️ Hypoglycaemia (particularly if on sulfonylureas ‼️)

SURPASS-4 (4/5)

Tolerability & safety of tirzpatide

📍Similar GI side-effects to GLP-1ra (i.e.🤢🤮💩)

📍Numerically fewer 4-point MACE events particularly after 52w 👍

SURPASS-4 (5/5)

📍🏆 standard ⤵️ HbA1c & ⤵️ weight

📍No new safety signal

📍Improvements in traditional CV risk factors

📍Numerically fewer 4-point MACE events

👏👏👏

📍 SURPASS-CVOT powered to formally CV safety/benefit 👇
clinicaltrials.gov/ct2/show/NCT04……

"Triple G" (1/4)

"Triple G" (2/4)

With tirzepatide we can see the benefits of dual over single incretin agonists.

So what about triple agonists (GIP/GLP-1/Glucagon)⁉️

Let us introduce you to @LillyPad latest exciting molecule
📍LY3437943 aka "Triple G"

"Triple G" (3/4)
📍🐭 study

✅ "Triple G" beats tirzepatide‼️ (well at least in 🐁)
⤵️ wt
⤴️ insulin secretion
⤴️ insulin sensitivity
⤵️ Liver fat content

👏👏👏

"Triple G" (4/4)

📍data from the 1st in human phase 1 study (n=47)
⚠️healthy human subjects

▶️ 6 day half-life. Making it ideal for QW dosing✅
▶️ GI side-effects "similar" to other incretins✅
▶️⤵️ wt & appetite✅
▶️⤴️ heart rate⚠️

‼️keep your 👀 on "Triple G"‼️

Keep checking the @cardiomet_CE account for more from #EASD2021

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...