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.
— cardio-met (@cardiomet_CE) July 7, 2021
Losing 5% to 10% of body weight through diet and exercise has been associated with a reduced risk of cardiovascular disease in adult patients with obesity or overweight pic.twitter.com/I4pk824CKi
— cardio-met (@cardiomet_CE) July 7, 2021
So – whilst we are talking about GLP-1 today a quick look at Liraglutide 3mg for the treatment of obesity… pic.twitter.com/iQmpf4dfDu
— cardio-met (@cardiomet_CE) July 7, 2021
— cardio-met (@cardiomet_CE) July 7, 2021
— cardio-met (@cardiomet_CE) July 7, 2021
So… what of semaglutide? pic.twitter.com/c3iWQPVXw9
— cardio-met (@cardiomet_CE) July 7, 2021
We know about the weight loss effects of GLP-1 RAs in T2DM…https://t.co/UNNi5meQsT pic.twitter.com/60tv3CsHHn
— cardio-met (@cardiomet_CE) July 7, 2021
So whilst this is effective, semaglutide 2.4mg has been aimed at supporting weight loss in those with obesity not specifically T2 diabetes . Will this high dose GLP-1 be any more effective? STEP this way… pic.twitter.com/gh09BSZf9K
— cardio-met (@cardiomet_CE) July 7, 2021
Check out this nice overview by @DrRobertKushner @profmjdavies et al https://t.co/r2hRNvUUXH
— cardio-met (@cardiomet_CE) July 7, 2021
Mean change in body weight from baseline to week 68 was:
— cardio-met (@cardiomet_CE) July 7, 2021
⬇️14.9% in the semaglutide group (-15.3kg) vs
⬇️2.4% with placebo (-2.6kg)
Weight loss
5% or more 1047[86.4%] vs.182 [31.5%]
10% or more 838 [69.1%] vs. 69 [12.0%]
15% or more 612 [50.5%] vs. 28 [4.9%] (P<0.001 for all)
— cardio-met (@cardiomet_CE) July 7, 2021
– Estimated change in mean bodyweight from baseline to week 68 was ⬇️9·6% with semaglutide 2·4 mg vs ⬇️3·4% with placebo.
— cardio-met (@cardiomet_CE) July 7, 2021
– More patients on semaglutide 2·4 mg than on placebo achieved weight reductions of at least 5% [68·8% vs 28·5%] (p<0·0001)
Gastrointestinal adverse events, which were mostly mild to moderate, were reported
— cardio-met (@cardiomet_CE) July 7, 2021
256 (63·5%) of 403 patients with semaglutide 2·4 mg
231 (57·5%) of 402 with semaglutide 1·0 mg
138 (34·3%) of 402 with placebo.
But it’s not just about adding a medication, what about in addition to lifestyle and diet? STEP forward…STEP 3 pic.twitter.com/yM4i5LB8RJ
— cardio-met (@cardiomet_CE) July 7, 2021
— cardio-met (@cardiomet_CE) July 7, 2021
803 participants
— cardio-met (@cardiomet_CE) July 7, 2021
20 week run in with semaglutide 2.4mg and mean weight loss 10.6%
Randomised to placebo or to continue semaglutide 2.4mg for 48 weeks
Mean body weight change from week 20 to week 68 was ⬇️7.9% vs ⬆️6.9% with the switch to placebo (p< .001)
— cardio-met (@cardiomet_CE) July 7, 2021
Waist circumference ⬇️9.7 cm, systolic BP ⬇️3.9 mm Hg and SF-36 physical functioning score all improved with continued subcutaneous semaglutide vs placebo (p<0.001)
Mean body weight change from week 20 to week 68 was ⬇️7.9% vs ⬆️6.9% with the switch to placebo (p< .001)
— cardio-met (@cardiomet_CE) July 7, 2021
Waist circumference ⬇️9.7 cm, systolic BP ⬇️3.9 mm Hg and SF-36 physical functioning score all improved with continued subcutaneous semaglutide vs placebo (p<0.001)
Albeit in a clinical trial setting…
— cardio-met (@cardiomet_CE) July 7, 2021
1. Semaglutide 2.4mg may provide significant weight loss in those with obesity/overweight with or w/out IBT in those with or w/out T2DM.
3. Side effect profile is as expected with GLP-1RAs with GI side effects mild-moderate and overall discontinuation rates low
— cardio-met (@cardiomet_CE) July 7, 2021
As a result… Semaglutide 2.4mg has very recently been approved by FDA June 4th 2021 as an adjunct to diet and exercise in obesity (BMI>/= 30) or overweight (BMI >27) with one weight related comorbidity https://t.co/bjFFvEzHRd
— cardio-met (@cardiomet_CE) July 7, 2021
So one last question…Would you consider semaglutide 2.4mg (approval allowing) for your patients with obesity?
— cardio-met (@cardiomet_CE) July 7, 2021
If you have made it this far congratulations! You deserve a 👏👏👏 this is @GoggleDocs signing off! #MedEd #obesity pic.twitter.com/M0Irjv740e
— cardio-met (@cardiomet_CE) July 7, 2021
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.
— cardio-met (@cardiomet_CE) July 8, 2021
Does it matter what HbA1c is when looking at the cardio-renal benefits of SGLT2i?
— cardio-met (@cardiomet_CE) July 8, 2021
Not according to these data from the largest SGLT2i CVOT (DECLARE TIMI_58)
Benefits of dapagliflozin were INDEPENDENT of baseline HbA1c (i.e even below 7% / 53mmol/mol)
ref: 788-P — 2021 pic.twitter.com/8Zw4maNsOp
Now moving on to #CKD
— cardio-met (@cardiomet_CE) July 8, 2021
@brendonneuen presented this image
Projected from the CREDENCE Trial (https://t.co/n3Wg4N765o)
📍Canagliflozin 100mg given to people with #type2diabetes plus albuminuric CKD (>300mg/g)
✅cana 100 could lead to postpoing dialysis by 15 years❗️❗️❗️ pic.twitter.com/To6wUjohv0
Canagliflozin 100mg when given to people with #type2diabets PLUS albuminuric CKD can delay need for renal replacement therapy by?
— cardio-met (@cardiomet_CE) July 8, 2021
We will be back with more learnings about SGLT2i in #HeartFailure this time with Preseved ejection fracture and the brave DARE-19 trail where dapagliflozin was used in people hospitalised with #Covid_19 pic.twitter.com/KwVI3oQhfY
— cardio-met (@cardiomet_CE) July 8, 2021
First up for today is the fascinating trial DARE-19 led by @MkosiborodMD
— cardio-met (@cardiomet_CE) July 9, 2021
Where dapagliflozin was trialled in a high risk cohort of hospitalised people with #COVID19 pic.twitter.com/6xpogTdGJb
SGLT2i also
— cardio-met (@cardiomet_CE) July 9, 2021
⤵️🏥with #HeartFailure in stable patients. & those benefits are rapid
From Soloist WHF https://t.co/GF5s6MSJXW
we see the ⤵️ in HF events in inpatients or recently discharged patients
So could SGLT2i be beneficial in these sick people? pic.twitter.com/pfr72PWChU
The primary endpoint (organ failure or death) dapagliflozin vs. placebo, was: 11.2% vs. 13.8% (p = 0.17).
— cardio-met (@cardiomet_CE) July 9, 2021
Primary outcome of recovery: Win ratio, 1.09 (95% CI 0.97-1.22, p = 0.14)
☠️: 6.6% vs. 8.6% (p > 0.05)
So a non-significant trend to benefit pic.twitter.com/75kjtzjqQE
Overall conclusion.
— cardio-met (@cardiomet_CE) July 9, 2021
📍DARE-19 demonstrated dapagliflozin was safe in patients with #COVID19 in closely monitored in-patients
📍It is possible that they may well be some benefits of using SGLT2i in terms of renal & cardiac adverse events
❓time to reappraise sick day rules
The role of SGLT2i in HFpEF⁉️ pic.twitter.com/h52JWv7Apn
— cardio-met (@cardiomet_CE) July 9, 2021
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
— cardio-met (@cardiomet_CE) July 9, 2021
Efpeglenatide is a GLP-1 receptor agonist once weekly injection but is not a human analogue but Exendin based GLP-1 (similar class to Lixisenatide and Exenatide) – first identified from the saliva of the Gila monster! #lizardspit pic.twitter.com/Ulq6brKOrF
— cardio-met (@cardiomet_CE) July 9, 2021
Those were human analogue GLP-1s….the Exendin based – namely lixisenatide and exenatide… not so much success… pic.twitter.com/oyYy3kROhf
— cardio-met (@cardiomet_CE) July 9, 2021
Exenatide once weekly came close to showing benefit but just missed out…https://t.co/1MOqzrUZMW
— cardio-met (@cardiomet_CE) July 9, 2021
But there was more than that to consider… pic.twitter.com/9j56Y8jhjI
— cardio-met (@cardiomet_CE) July 9, 2021
Standard design…however they allowed for current and future SGLT2 use! pic.twitter.com/bQ1dgwb4u1
— cardio-met (@cardiomet_CE) July 9, 2021
These CVOTs are designed for glycaemic equipoise – i.e. blood sugars should be kept similar in both intervention and treatment groups. Despite this, due to the efficacy of the molecule, Efpeglenatide showed metabolic benefits…
— cardio-met (@cardiomet_CE) July 9, 2021
So… what of the CV outcomes….👇🏽 pic.twitter.com/y1ncmzfpK2
— cardio-met (@cardiomet_CE) July 9, 2021
Additionally an interesting 32% reduction in the renal composite outcome! pic.twitter.com/PU79LDNWc4
— cardio-met (@cardiomet_CE) July 9, 2021
⭐️ Benefits seen irrespective of baseline SGLT2 use⭐️ pic.twitter.com/yUEjvf27vf
— cardio-met (@cardiomet_CE) July 9, 2021
Some other points:
— cardio-met (@cardiomet_CE) July 9, 2021
➡️ Will the GLP-1/SGLT2 group show added benefit in further analyses? (not powered enough)
➡️ The renal data is one of the strongest for the GLP-1 class
➡️ Suggestion of heart failure benefit ( HR 0.61 CI 0.38-0.98) – a first for a GLP-1 ( but small numbers)
Very good data indeed…just one more thing….
— cardio-met (@cardiomet_CE) July 9, 2021
currently Efpeglenatide is not available to prescribe (🇺🇸🇬🇧🇪🇺) so similarly to Albiglutide…great data but not much we can do…for now!
That's all for now from @GoggleDocs Look forward to welcoming you to our final tweetorial later today on a new class of medications: the GIP-GLP1 dual agonists! pic.twitter.com/zGXfaiojCk
— cardio-met (@cardiomet_CE) July 9, 2021
So is Tirzepatide just a really good GLP-1ra or "does that GIP do the trick?"
— cardio-met (@cardiomet_CE) July 9, 2021
What does @DanielJDrucker think?
👇
From mice models
— cardio-met (@cardiomet_CE) July 9, 2021
GIP only lowers glucose when glucose close to normal
(data not shown)
In GLP-1 knockout mice Tirzepatide is much better at weight loss compared to semaglutide
So GIP may do the trick for weight, and.possibly in glucose if near normal. pic.twitter.com/MN5950yggf
Yup the 15mg dose of Tirzeptide
— cardio-met (@cardiomet_CE) July 9, 2021
⤵️weight by >10% = 47%❗️
⤵️weight by >15% = 27%🙂
⤴️⤴️🤢🤮💩 (To me the 5mg looks the best balanced) pic.twitter.com/5pM17cbTxl
A word of caution.
— cardio-met (@cardiomet_CE) July 9, 2021
Excess of deaths in all three of the Tirzepatide arms.
They have been reported as half from #covid19 and the others at very high CV risk.
Fortunately there is a Cardiovascular Outcome trial of Tirzepatide vs Dulaglutide.
SURPASS-CVOThttps://t.co/diGj6Aatfr pic.twitter.com/3tSthusQXO
Tirzepatide – "does it take two.."… "to make a dream come true?"
— cardio-met (@cardiomet_CE) July 9, 2021
⤵️HbA1c against 🥇 standard therapy
⤵️weight against 🥇gold standard therapy
⤴️🤢🤮💩
⚠️Investigational drug only
⚠️⤴️☠️ in one of 4 studies, although maybe related to #COVID19 pic.twitter.com/YjZhnfstjN
Now let's shift gear to p
— cardio-met (@cardiomet_CE) July 9, 2021
our favorite class of drug. Lets #flozinate !
No big presentation of a big #HeartFailure outcome trial 🙁. These days they are always it's @ESC_Journals or @AHAMeetings .
Maybe one of these days we will have a CaReMe/CadiometabolicConference?
So I for one can't wait for the @escardio conference for the results of the pivotal EMPEROR-Preserved Trial. pic.twitter.com/vXVv3iNAcJ
— cardio-met (@cardiomet_CE) July 9, 2021
Guess what? pic.twitter.com/c6O8BFPYxi
— cardio-met (@cardiomet_CE) July 9, 2021
"So that's all folks.
— cardio-met (@cardiomet_CE) July 9, 2021
Time to hand the key to the @cardiomet_CE account back to the magic wizard pic.twitter.com/toLQVvWQj3