#1085

Nope no access to that.

1 Like
#1086

I read this more carefully, and with my limited English skills, I concluded that it lists three categories: insulin analogues, empagliflozin, and canagliflozin, and states that their potential effect on EF are limited. So, it doesnā€™t claim that empagliflozin or canagliflozin are insulin analogues :slightly_smiling_face:

3 Likes
#1087

I have been feeling rather sleepy, weak and craving carbs in the past few weeks and my HbA1c is nearing the the lower 4.0 mark, so I am considering multiple options.

  1. lowering my current 12.5mg dose to 6.25mg
  2. taking 12.5mg in the evening only so that during the day my body has more sugar available
  3. taking it less regularly

Which option would you go for and why?

#1088

4% HbA1c?! This means an average glucose of 3.8 mg/dL so you might often be in hypoglycemia. Do you wear a CGM? Which other glucose lowering drugs do you take? (telmisartan lowers it a bit)

2 Likes
#1089

I only take 12.5mg empagliflozin and 20mg telmisartan. And yeah I think I could be in hypoglycemia although it hasnā€™t harmed my gym performance yet.

1 Like
#1090

Wear a CGM and check. Over time you can develop hypoglycemia unawareness.

5 Likes
#1091

Tj-long, I thinnk you are right! Yeah, now everything makes sense.

2 Likes
#1092

ā€œThe efficacy of combining two beneficial antidiabetes interventions, regular endurance exercise and SGLT2 inhibition, was not supported. SGLT2 inhibition blunted endurance exercise training-induced improvements in insulin sensitivity, independent of effects on aerobic fitness or body composition.ā€ :thinking:

My theory on this is that the SGLT2i group has better fat metabolism, and glycogen stores are significantly depleted due to the SGLT2i medication and exercise, leading to a sharper rise in blood sugar after the workout. Iā€™ve personally noticed, even without SGLT2 medications, that my blood sugar rises very easily after a long Zone 1-2 workout. I once posted a study here showing that well-trained individuals experienced a higher rise in blood sugar after a post-workout meal compared to less fit individuals.

Itā€™s also interesting that endurance sports increase plasma volume, whereas SGLT2i reduces it. As I understand it, an increased plasma volume is one reason for a drop in resting heart rate. Has anyone noticed that SGLT2i raises resting heart rate?

Btw, some interesting comments in the study about metformin, statins, etc

5 Likes
#1093

Probably (hopefully!) not applicable to the audience of that forum.

#1094

Have you looked at creatinine clearance before cana and after?

1 Like
#1095

I havenā€™t noticed this.

3 Likes
#1096

SGLT2 inhibitors protect against diabetic cardiomyopathy and atrial fibrillation through a CaMKII independent mechanism 2024

:warning: Preprint (but Johns Hopkins University) :warning:

Ca2+/calmodulin-dependent protein kinase II (CaMKII) has been implicated as an important mediator of the increasingly evident cardioprotective benefits exerted by sodium- glucose transport protein 2 channel inhibitors (SGLT2i). However, the exact nature of the relationship between CaMKII and SGLT2i remains unclear. Here, we find that empagliflozin but not dapagliflozin attenuated susceptibility to atrial fibrillation (AF) in a type 2 diabetic (T2D) mouse model. However, both empagliflozin and dapagliflozin protected from diabetic cardiomyopathy in T2D mice. We then used real-time microscopy of neonatal rat ventricular cardiomyocytes (NRVMs) with the CaMKII biosensor - CaMKAR to demonstrate that direct inhibition of CaMKII is not essential for the effects of SGLT2i in these cells. Therefore, we conclude that the benefits of SGLT2i in heart disease likely occur through indirect modulation of CaMKII activity, or possibly through an alternative pathway altogether.

4 Likes
#1097

On the other hand:

This realā€world, populationā€based study demonstrates that patients with type 2 diabetes using dapagliflozin may have a lower risk of developing nonvalvular atrial fibrillation than those using empagliflozin.

4 Likes
#1098

That study is a very interesting find, tj-long. I have some thoughts on this which Iā€™ll put down when I have a bit of time. Meanwhile, hereā€™s a funny counterpoint, reaching the opposite conclusions, which wouldā€™ve been very interesting, except it is in mice - and mice that have been brutalized into diabetes - and using canagliflozin instead of dapagliflozin, by folks associated with Pfizer, so not exactly actionable material by any sane person:

However I may have been a bit unfair, since a different group, although still somewhat pharma adjacent came to the same result (again, mice bludgeoned into diabetes, exercise and canagliflozin):

https://journals.physiology.org/doi/full/10.1152/ajpendo.00401.2019?rfr_dat=cr_pub++0pubmed&url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org

And of course a study in humans (in this case not diabetic, although overweight and sedentary), trumps mice every day of the week and twice on Sunday :slight_smile:

Though in all fairness, is it possible that if they used canagliflozin like in the mice, is it conceivable that the results may have been different, or more remote possibility, perhaps itā€™s specific to dapagliflozin and a different SGLT2i, say empagliflozin might give a different outcome (seems very unlikely!)?

1 Like
#1099

I personally believe that itā€™s due to the simple fact that the SGLT2i group has, on average, fewer glycogen stores available, and the body adapts more to fat burning. When you eat after a workout, this is just a temporary reaction, and I donā€™t think it has any negative impact on health. Overall, SGLT2i reduces insulin resistance.

3 Likes
#1100

That makes sense to me as I no longer develop a ā€œcarb-stomachā€ even after eating lots of carbs.

1 Like
#1101

Here is a chart from this paper:

image
image1920Ɨ1321 216 KB

VO2 Max looks good in EX + SGLT2, but itā€™s calculated per kg. So if we care about absolute VO2 Max (volume per minute), we can multiply by weight. This would give us:
EX: 2,385
EX + SGLT2: 2,250

1 Like
#1102

Chinese paper, fwiw: The role and mechanism of dapagliflozin in Alzheimer disease: A review 2024

This article offers a comprehensive overview of the research progress on DAPA in AD, encompassing key findings from preclinical studies to clinical trials. The abundance of in vivo and in vitro evidence indicates that DAPA exerts a beneficial impact on reducing the risk of dementia. Its mechanisms may encompass antioxidative stress, antineuroinflammation, upregulation of autophagy, antiapoptosis, AChE inhibitor activity, and protection of endothelial cells against AS and BBB damage.

5 Likes
#1103

I challenge anyone to start on top of this tread and read everything including all links attached.

9 Likes
#1104

Korean paper: Sodium-glucose Cotransporter-2 Inhibitors versus Dipeptidyl Peptidase IV Inhibitors and Risk of Dementia Among Patients with Type 2 Diabetes and Comorbid Mental Disorders: A Population-based Cohort Study 2024

Over a 4.8-year median follow-up, SGLT2 inhibitors were associated with a 12% lower risk of dementia compared with DPP4 inhibitors (11.31 vs. 12.86 events per 1000 person years; HR 0.88, 95% CI 0.84 to 0.92; RD -1.55, -2.13 to -0.97). The results were consistent when stratified by age, sex, individual component, severe mental disorders, presence of insulin, history of cardiovascular disease, or history of hypertension.

The HR is not as good as previous studies. Is it because itā€™s a very high-risk population? Or because the HR is per year (instead of over the whole follow-up period?)?

3 Likes