It’s the beginning of the end for tirzepatide

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SUMMIT showed 38% risk reduction of heart failure outcomes, but with a numerical imbalance in both CV and all-cause mortality favouring placebo. Placebo patients gained weight and still had better CV and all-cause mortality outcomes.
 


anonymous said:
SUMMIT showed 38% risk reduction of heart failure outcomes, but with a numerical imbalance in both CV and all-cause mortality favouring placebo. Placebo patients gained weight and still had better CV and all-cause mortality outcomes.
Click to expand...
Hard numbers from SUMMIT TRIAL


1. Weight loss % of body weight Zepbound 15.7%, Placebo 2.2%


2. CV death Zepbound 2.2%, Placebo 1.4% 58% less CV death for placebo


3. All cause mortality Zepbound 5.2%, Placebo 4.1% 25% less all cause mortality deaths for placebo
 


anonymous said:
SUMMIT showed 38% risk reduction of heart failure outcomes, but with a numerical imbalance in both CV and all-cause mortality favouring placebo. Placebo patients gained weight and still had better CV and all-cause mortality outcomes.
Click to expand...
Hard numbers from SUMMIT TRIAL


1. Weight loss % of body weight Zepbound 15.7%, Placebo 2.2%


2. CV death Zepbound 2.2%, Placebo 1.4% 58% less CV death for placebo


3. All cause mortality Zepbound 5.2%, Placebo 4.1% 25% less all cause mortality deaths for placebo
 








Meh. Most people want these drugs for weight loss. Lilly will just drop the price for coverage sakes if needed.

Trulicity has a primary and secondary indication and it didn’t move the needle
 


anonymous said:
Hard numbers from SUMMIT TRIAL


1. Weight loss % of body weight Zepbound 15.7%, Placebo 2.2%


2. CV death Zepbound 2.2%, Placebo 1.4% 58% less CV death for placebo


3. All cause mortality Zepbound 5.2%, Placebo 4.1% 25% less all cause mortality deaths for placebo
Click to expand...
Thank you. This is very interesting. Up until now, there has been an assumption that weight loss correlates with CV event reduction. Seems like it depends on how you lose weight is what matters.
 


anonymous said:
Hard numbers from SUMMIT TRIAL


1. Weight loss % of body weight Zepbound 15.7%, Placebo 2.2%


2. CV death Zepbound 2.2%, Placebo 1.4% 58% less CV death for placebo


3. All cause mortality Zepbound 5.2%, Placebo 4.1% 25% less all cause mortality deaths for placebo
Click to expand...
Someone taking these types of drugs are likely weakening their heart due to a loss of heart muscle. Also, long-term use of these types of drugs will likely induce early onset of osteoporosis, or decrease bone density to some extent. I made similar predictions eighteen-ish months ago.
 


God said:
Someone taking these types of drugs are likely weakening their heart due to a loss of heart muscle. Also, long-term use of these types of drugs will likely induce early onset of osteoporosis, or decrease bone density to some extent. I made similar predictions eighteen-ish months ago.
Click to expand...
Meal associated bone remodeling increases with GLP-1, and it’s remodeling is double that with GIP. So both hormones do not decrease bone density but are active in bone density remodeling.
 


anonymous said:
Meal associated bone remodeling increases with GLP-1, and it’s remodeling is double that with GIP. So both hormones do not decrease bone density but are active in bone density remodeling.
Click to expand...
I've read that. I expect bone density to be negatively impacted through the decrease in skeletal muscles.
 




Usually, when people eat less the pancreas produces less needed insulin. With mega doses of these laboratory engineered synthetic long acting GLP1 hormones, the healthy pancreas is unnaturally and constantly stimulated to produce and store insulin that is needed less because of less consumed calories and weight loss. Slowed gastric emptying is separate from unnatural pancreatic stimulation. Pancreatitis is in package insert and is a known risk factor for pancreatic cancer. Lawyers are going to have a field day. Everyone’s pension will be affected and most will be fired. The body produces GLP1 that has a duration of action of a few minutes not weeks like laboratory engineered GLP1.
 


anonymous said:
Hard numbers from SUMMIT TRIAL


1. Weight loss % of body weight Zepbound 15.7%, Placebo 2.2%


2. CV death Zepbound 2.2%, Placebo 1.4% 58% less CV death for placebo


3. All cause mortality Zepbound 5.2%, Placebo 4.1% 25% less all cause mortality deaths for placebo
Click to expand...
where did you get access to this data?
 


anonymous said:
Usually, when people eat less the pancreas produces less needed insulin. With mega doses of these laboratory engineered synthetic long acting GLP1 hormones, the healthy pancreas is unnaturally and constantly stimulated to produce and store insulin that is needed less because of less consumed calories and weight loss. Slowed gastric emptying is separate from unnatural pancreatic stimulation. Pancreatitis is in package insert and is a known risk factor for pancreatic cancer. Lawyers are going to have a field day. Everyone’s pension will be affected and most will be fired. The body produces GLP1 that has a duration of action of a few minutes not weeks like laboratory engineered GLP1.
Click to expand...
Lolol
This guy again
 




anonymous said:
Thank you. This is very interesting. Up until now, there has been an assumption that weight loss correlates with CV event reduction. Seems like it depends on how you lose weight is what matters.
Click to expand...
yeah im confused this is directly from the NEJM:

A total of 364 patients were assigned to the tirzepatide group and 367 to the placebo group; the median duration of follow-up was 104 weeks. Adjudicated death from cardiovascular causes or a worsening heart-failure event occurred in 36 patients (9.9%) in the tirzepatide group and in 56 patients (15.3%) in the placebo group (hazard ratio, 0.62; 95% confidence interval [CI], 0.41 to 0.95; P=0.026). Worsening heart-failure events occurred in 29 patients (8.0%) in the tirzepatide group and in 52 patients (14.2%) in the placebo group (hazard ratio, 0.54; 95% CI, 0.34 to 0.85), and adjudicated death from cardiovascular causes occurred in 8 patients (2.2%) and 5 patients (1.4%), respectively (hazard ratio, 1.58; 95% CI, 0.52 to 4.83). At 52 weeks, the mean (±SD) change in the KCCQ-CSS was 19.5±1.2 in the tirzepatide group as compared with 12.7±1.3 in the placebo group (between-group difference, 6.9; 95% CI, 3.3 to 10.6; P<0.001). Adverse events (mainly gastrointestinal) leading to discontinuation of the trial drug occurred in 23 patients (6.3%) in the tirzepatide group and in 5 patients (1.4%) in the placebo group.
 


anonymous said:
yeah im confused this is directly from the NEJM:

A total of 364 patients were assigned to the tirzepatide group and 367 to the placebo group; the median duration of follow-up was 104 weeks. Adjudicated death from cardiovascular causes or a worsening heart-failure event occurred in 36 patients (9.9%) in the tirzepatide group and in 56 patients (15.3%) in the placebo group (hazard ratio, 0.62; 95% confidence interval [CI], 0.41 to 0.95; P=0.026). Worsening heart-failure events occurred in 29 patients (8.0%) in the tirzepatide group and in 52 patients (14.2%) in the placebo group (hazard ratio, 0.54; 95% CI, 0.34 to 0.85), and adjudicated death from cardiovascular causes occurred in 8 patients (2.2%) and 5 patients (1.4%), respectively (hazard ratio, 1.58; 95% CI, 0.52 to 4.83). At 52 weeks, the mean (±SD) change in the KCCQ-CSS was 19.5±1.2 in the tirzepatide group as compared with 12.7±1.3 in the placebo group (between-group difference, 6.9; 95% CI, 3.3 to 10.6; P<0.001). Adverse events (mainly gastrointestinal) leading to discontinuation of the trial drug occurred in 23 patients (6.3%) in the tirzepatide group and in 5 patients (1.4%) in the placebo group.
Click to expand...
Under primary endpoints and components (table 2), The very first heading is the Composite MACE for the trial stated "adjudicated death from cardiovascular causes OR a worsening of heart failure..." and yes that is positive when all the data is looked at together. Then all the sub headings under the first heading is each single MACE individually. Looking at the composite MACE only makes it look like there's not a potential issue because the data looks good because of the heart failure component in the MACE, so it makes everything look good. When you looks at the CV death and All cause death component individually that's when you seen that Placebo did better. Remember Jardiance did a three point composite MACE and only was awarded a CV death indication and not MI or Stroke because Individually MI and Stroke failed to meet a positive outcome.
 





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