Clarification: My excitement isn’t necessarily just about this one study, or these particular compounds. It’s the fact that there are massive incentives for pharmaceutical companies to come up with new solutions in the area of muscle maintenance, muscle gain and strength gain. This will have massive implications on society as a whole helping people who otherwise just don’t have the motivation to improve their body composition.
Original post:
Ok this is actually crazy.
The muscle loss side effects of GLP1 agonists come from poor doctor guidance and patient compliance with altering protein % of macronutrients and performing resistance training to make up for the lower calorie consumption that comes with GLP1 agonist use.
The bright side of this: Due to muscle loss side effects from GLP1 agonists pharma companies have been working on a brand new range of muscle building drugs.
2 new drugs are being tested in combination with semaglutide:
1. Trevogrumab - Myostatin inhibitor
2. Garetosmab - Activin-A inhibitor
4 different groups:
Group 1: Monkeys without semaglutide and on a diet lost 400g body fat and lost 15g muscle.
Group 2: Monkeys with semaglutide lost about 700g body fat but lost about 100g of muscle.
Group 3: Monkeys with semaglutide and trevogrumab lost about 1300g of body fat and lost about 15g of muscle.
Group 4: Monkeys with semaglutide, trevogrumab and garetosmab lost about 1400g of body fat but gained 450g of muscle!
Unknown side effects aside I think this is very impressive.
My main concern with anything that can increase muscle is increasing the size of the heart.
There is evidence that GLP1 agonists prevent heart hypertrophy however:
Evidence that tirzepatide protects against diabetes-related cardiac damages: “Our findings indicate that TZT has beneficial effects on cardiac cells by positively modulating cardiomyocyte death, fibrosis, and hypertrophy in the presence of high glucose concentrations. This suggests that TZT may reduce the risk of diabetes-related cardiac damage, highlighting its potential as a therapeutic option for heart failure management clinical trials. Our study strongly supports the rationale behind the clinical trials currently underway, the results of which will be further investigated to gain insights into the cardiovascular safety and efficacy of TZT.”
Tirzepatide Reduces LV Mass and Paracardiac Adipose Tissue in Obesity-Related Heart Failure: SUMMIT CMR Substudy: “The CMR substudy of the SUMMIT trial demonstrated that tirzepatide therapy in obesity-related HFpEF led to reduced LV mass and paracardiac adipose tissue as compared with placebo, and the change in LV mass paralleled weight loss. These physiologic changes may contribute to the reduction in heart failure events seen in the main SUMMIT trial. (A Study of Tirzepatide [LY3298176] in Participants With Heart Failure With Preserved Ejection Fraction [HFpEF] and Obesity: The SUMMIT Trial”
Tirzepatide attenuates lipopolysaccharide-induced left ventricular remodeling and dysfunction by inhibiting the TLR4/NF-kB/NLRP3 pathway: “In brief, tirzepatide attenuates LPS-induced left ventricular remodeling and dysfunction by inhibiting the TLR4/NF-kB/NLRP3 pathway.”
Effects of tirzepatide on circulatory overload and end-organ damage in heart failure with preserved ejection fraction and obesity: a secondary analysis of the SUMMIT trial: “Tirzepatide reduced cardiac injury, reflected by decreases in troponin T, and reduced wall stress, reflected by decreases in NT-proBNP”