#1606

Dapagliflozin alleviates mitochondrial damage in the myocardium under diabetic conditions by targeting sortilin 2025

Our findings uncover a novel molecular mechanism through which dapagliflozin improves myocardial mitochondrial injury under diabetic conditions, suggesting SORT1 as a potential therapeutic target for treating myocardial injury in diabetes.

3 Likes
#1607

Can you talk more to this?

1 Like
#1608

Will take a look.

@AnUser @adssx - Is this a 2013 packet? But the result was never published in a paper?

2 Likes
#1609

Thatā€™s from the 104 week (2-year) carcinogenicity rat or mouse study that it seems most drugs have to do.

See this post:

3 Likes
#1610

blsm, I think of exercise as being 4 to 5 zones with a level 2 being a steady walk (and talk) for a mile or two before moving into a fast walk with very limited conversation as zone 3. From there itā€™s jogging (level 3) and sprinting (level 4). Can you describe your zone 2? I ask because Iā€™ll be trying Empagliflozin soon, but I hate to think that it could mess up my exercise routines.

1 Like
#1611

@AnUser @adssx

Did you see Matt Kā€™s comment on the other thread:

ā€(2) Lifespan studies are not carcinogenicity studies. Perhaps that wasnā€™t what the comment intended, but this is what it sounded like.ā€

What are your thoughts? Iā€™d rather believe your point that this FDA packet provided longevity data - but is Matt saying that it is not that helpful? Or did he not understand the packet?

1 Like
#1612

I think Matt was addressing a separate point as

ā€œā€¦ at relativley low cost (compared to the cost of moving an unworthy drug forward) in less than a year by starting in 24 month old mice.ā€ and

ā€œā€¦ assuming the goal is a geroprotector, not an incremental disease drug.ā€, etc, sound to me that Matt believes they were carcinogenicity studies in name only, basically what those studies are called.

The everolimus study I posted in that thread seems to have had a nice +25% effect on 104 week lifespan compared with control, and decrease in age-related effects, statistical significance testing aside, if you can take a look and if you agree.

2 Likes
#1613

Sure, I canā€™t decide if this change is good or bad yet. At first I was leaning towards good but now Iā€™m not so sure. Hereā€™s a little background and caveats: Iā€™m a 55 y/o female, not an athlete or very knowledgeable about fitness but Iā€™m pretty active. Fitbit fwiw gives me an excellent cardio fitness score of 43-47.
I average 10k steps per day, do sprint intervals for 15 minutes 1x/week, ruck for @40 minutes with 10-25% of my body weight 4-5x/week and lift weights 2-3x/week. I could easily achieve my goal of 40 total zone minutes per day without having to try before starting dapagliflozin. Fitbit breaks them down into moderate, vigorous and peak and around 75-80% of my zone minutes would be moderate and the remaining 20-25% vigorous/peak. I also wear a 10% weighted vest around doing my normal daily activities for a minimum of 2-4 hours daily but sometimes more.
I used to at least be in zone 2 or moderate for most of the time anytime I rucked and now doing the same thing I may not get my heart rate above 100 at all or for less than 5 minutes. I ruck on uneven terrain with small hills. I did discover recently that I can get into zone 3 or higher fairly easily on a stationary bike at the gym so perhaps itā€™s coincidental that I noticed this shortly after starting dapagliflozin and Iā€™m simply adapted to rucking and needed a new challenge?!?!
It seems to be doing something good for my cardiovascular system so far where I have to work harder than I used to get into zone 2 or higher but perhaps Iā€™m interpreting things incorrectly? Iā€™m considering getting a more detailed tracker and Iā€™m trying to learn and understand all of this more. I didnā€™t really start working on my fitness until 5 years ago and didnā€™t really need to understand it much to see results until recently. My husband says Iā€™ve plateaued. I hope that long winded rambling helps!

3 Likes
#1614

@blsm

Fitbit fwiw gives me an excellent cardio fitness score of 43-47.
I average 10k steps per day, do sprint intervals for 15 minutes 1x/week, ruck for @40 minutes with 10-25% of my body weight 4-5x/week and lift weights 2-3x/week.

Just had to commentā€¦ pretty impressive! Finding the time to do all that is part of the difficulty. I do a walk the dog ruck that helps kill two birds.

I think the Attia/Inigo San millan crowd defines exercise routines into three zones. Zone 1 is (I believe) similar metabolically to zone 2 but not maxing out the pathway. Zone 2 is defined as the point where you are maximizing your mitochondrial respiration for the production of ATP and generally corresponds to somewhere around 80% of maximal heart rate. Thus you are burning fats and getting maximal ATP from the process and not producing a lot of lactic acid. As you hit the next zone 3 you are unable to keep up with the activity using respiration so you begin using less efficient but more readily available energy substrates that are converted to ATP by anaerobic pathways and you begin to accumulate lactic acid.

2 Likes
#1615

Thank you! Iā€™m trying to understand all of the better! @Joseph_Lavelle has been very helpful as well! I love this place.

1 Like
#1616

Effects of Empagliflozin on Sarcopenia Risk, Body Composition, and Muscle Strength in Type 2 Diabetes: A 24-Week Real-World Observational Study 2025

Turkish paper + MDPI so low quality but:

Results: The empagliflozin group showed significant improvements in HbA1c, fasting plasma glucose, body weight, waist circumference, and fat mass (p < 0.05 for all). No significant changes were observed in the empagliflozin group after 6 months in appendicular skeletal muscle mass index (from 7.81 Ā± 1.33 kg/m2 to 7.84 Ā± 1.38 kg/m2, p = 0.154). No statistically significant changes were observed in handgrip strength in either group.
Conclusions: Empagliflozin treatment over six months led to favorable changes in metabolic parameters and fat mass without detrimental effects on skeletal muscle mass or muscle strength. In clinical practice, the selection of antidiabetic therapies should consider individual glycemic targets, cardiovascular and renal risks, weight management, comorbidities and sarcopenia risk. Resistance exercises and adequate dietary protein intake should be recommended to preserve muscle mass in at-risk patients. Larger randomized trials are needed to confirm the long-term effects of SGLT2 inhibitors on body composition particularly in older adults.

9 Likes