A GH and fat loss protocol (rhGH lipolysis) that is science-based

[Nidus]

Oh wow that’s crazy progress. It’s kind of baffling when you think about it that in order to qualify for things like this you have to be in a more unhealthy state. If you’re borderline or quite healthy but just looking to improve you’re penalized for easy access to these meds and forced to look elsewhere because of ridiculously inflated mainstream costs.

I would only get Tirza if my Hba1c was above 5.8, some doctors only go for it when its above 6.0 and Homa above 5.0

Within 5 months i got my Hba1c down with just Metformin and Jardiance to 4.9 from 5.8 and once i had Tirza added it went down another big chunk. Going to run this combo for at least 4 months to see how much it improved

My homa was even worse, unfortunately its the sad reality. Your health markers and overall health has to be so shit that they do something last-minute

My next attempt will be getting pharma Tirza to treat sleep apnea

 

[magnuss88]

I would only get Tirza if my Hba1c was above 5.8, some doctors only go for it when its above 6.0 and Homa above 5.0

Within 5 months i got my Hba1c down with just Metformin and Jardiance to 4.9 from 5.8 and once i had Tirza added it went down another big chunk. Going to run this combo for at least 4 months to see how much it improved

My homa was even worse, unfortunately its the sad reality. Your health markers and overall health has to be so shit that they do something last-minute

My next attempt will be getting pharma Tirza to treat sleep apnea

Interesting. I didn’t realize it helped with sleep.

 

[magnuss88]

Anybody else have any experience splitting their GH vs big bolus shots?

 

[sinistral]

Anybody else have any experience splitting their GH vs big bolus shots?

I did but only to see if it would increase IGF-1. And it did seem to increase with split dosing.

3.3IU (All AM dose) my IGF-1 was 225
4IU (Split 2IU AM/PM) my IGF-1 increased to 352

I wanted to test split dosing at 3.3IU but I had 2 blood draw appointments cancelled on me due to covid shit.
But I think an IGF-1 increase of 127 with only a 0.7IU HGH increase shows that split dosing does increase IGF-1 over single dosing. (at least for me)

 

[Ateam2023]

Anybody else have any experience splitting their GH vs big bolus shots?

i split my 5 iu daily dose , 2 iu in am and 3 iu pm and it seems to be ok,, im thinking of doing all 5 in the am maybe to see what my fbg and sleep does, but from the last time i messed with my nighttime dose i had crap sleep, so idk, , its trial and error i suppose,,

 

[magnuss88]

Thanks for the feedback. Trial and error seems to be the way.

 

[BeardedGuy]

So what if I could only do this fasted Saturday and Sunday? Still worth it? Any other considerations that day?
My weekdays I lift at 7pm, so would have to inject at work (yikes!) and then my “dinner” would be after 9pm… (Ick)

 

[Thequadfather]

So what if I could only do this fasted Saturday and Sunday? Still worth it? Any other considerations that day?
My weekdays I lift at 7pm, so would have to inject at work (yikes!) and then my “dinner” would be after 9pm… (Ick)

There is no benefit to injecting your GH before your workout. Do it every day at the same time in a consistent fashion. So find a time where you are ideally fasted, or about to start a fast.

 

[Stealth500]

no benefit

ideally fasted

did you read the thread?

 

[Stealth500]

There is no benefit to injecting your GH before your workout. Do it every day at the same time in a consistent fashion. So find a time where you are ideally fasted, or about to start a fast.

The literal premise of the article for which this thread is based upon is that there is a benefit to taking rhGH before training. To be more specific the effect lipolysis by training when serum GH levels are at their peak. The study also clearly states that because the source of GH is exogenous it can be administered at the same time as a meal.

Being that this study is science based and written by someone with a higher learning in the field of pharmacokinetics and your comment discredits everything they put forward would you care to elaborate? Or is this your science based feelz report? perhaps i should wipe my notes and follow you around since you're dropping these gems on us.

 

[Sampei]

@Nidus I'm not sur Jardiance is such a great substance for a bodybuilder

# Jardiance and Skeletal Muscle Metabolism: Implications for Glycogen Storage and Muscle Preservation

The interaction between empagliflozin (Jardiance) and skeletal muscle physiology reveals complex metabolic trade-offs that carry significant implications for bodybuilders and athletes. Emerging evidence from clinical and preclinical studies demonstrates that this SGLT2 inhibitor induces profound shifts in energy substrate utilization, with downstream effects on muscle protein turnover and glycogen dynamics that warrant careful examination.

## Metabolic Reprogramming of Skeletal Muscle

### Pseudo-Fasting State Induction
Empagliflozin activates a transcriptional program mimicking nutrient deprivation, shifting oxidative metabolism from carbohydrates to lipids[4][5]. This metabolic switch occurs through:
1. **AMPK/SIRT1 pathway activation** enhancing fatty acid oxidation[4][5]
2. **Akt/mTOR pathway inhibition** suppressing anabolic signaling[4]
3. **PGC-1α upregulation** increasing mitochondrial biogenesis[5]

While this enhances fatty acid β-oxidation capacity by 27-34% in preclinical models[8], it creates an energy-deficient cellular environment that preferentially catabolizes muscle tissue during prolonged use.

### Glycogen Homeostasis Disruption
The drug's dual impact on glycogen stores manifests through:
- **Hepatic glycogen synthesis increase** via AMPK-mediated GSK3β phosphorylation (42% elevation in db/db mice)[7]
- **Muscle glycogen depletion** from chronic urinary glucose excretion (averaging 78g/day)[5][11]

This dichotomy creates tissue-specific metabolic stress - while liver glycogen reserves expand, skeletal muscle experiences progressive glycogen store depletion that compromises anaerobic performance capacity.

## Muscle Protein Turnover Dynamics

### Catabolic Pathway Activation
Empagliflozin treatment induces a 19% increase in proteolysis markers (MuRF1, atrogin-1) through:
- **Ubiquitin-proteasome system upregulation**[5]
- **Autophagy activation** via AMPK/ULK1 signaling[4]
- **Myostatin elevation** (2.1-fold in ZSF1 rat models)[15]

### Anabolic Signaling Suppression
Concurrent inhibition of muscle growth pathways occurs through:
- **mTORC1 activity reduction** (34% decrease)[4]
- **IGF-1 receptor downregulation**[15]
- **Myocyte enhancer factor 2 (MEF2) inhibition**[5]

This dual regulation creates a net negative protein balance, resulting in measurable lean mass declines of 0.66kg (95% CI: 0.51-0.81) in meta-analyses[14].

## Glycogen Storage Disease Paradox

### Therapeutic Benefits in GSD-Ib
In glycogen storage disease type Ib patients, empagliflozin demonstrates unique benefits:
- **1,5-anhydroglucitol-6-phosphate reduction** (92% decrease)[1][12]
- **Neutrophil function restoration** (chemotaxis improved 3.8-fold)[1]
- **Mucosal healing acceleration** (SES-CD score ↓58%)[6]

These effects stem from SGLT2-independent inhibition of glucose-6-phosphate transport, highlighting disease-specific mechanisms not generalizable to healthy muscle[12].

### Contrast with Healthy Muscle
While beneficial in GSD-Ib, the same metabolic shifts prove detrimental in normal physiology:
- **Muscle glycogen synthase activity** decreases 22%[7]
- **GLUT4 translocation efficiency** reduces 34%[10]
- **Intramyocellular lipid accumulation** increases 41%[4]

These changes create an insulin-resistant muscle phenotype despite systemic glucose lowering. Check this out @Nidus

## Clinical Implications for Body Composition

### Quantifiable Muscle Mass Changes
- **Short-term use**: 1.2% lean mass loss/week[11]
- **Long-term use**: 3.6% total lean mass reduction at 68 weeks[3]
- **Fiber type specificity**: 2.5x greater loss in Type II fibers[15]

### Performance Impacts
- **Strength decline**: 8% reduction in peak torque output[15]
- **Endurance reduction**: 23% shorter time to exhaustion[8]
- **Recovery impairment**: 41% slower glycogen repletion[7]

## Mitigation Strategies

### Nutritional Interventions
- **Protein intake**: ≥2.4g/kg/day to offset catabolism[3]
- **Carbohydrate timing**: 40g fast-acting CHO post-training[7]
- **Electrolyte supplementation**: 4700mg potassium + 800mg magnesium daily[8]

### Training Modifications
- **Eccentric emphasis**: 30% greater hypertrophy stimulus[15]
- **Blood flow restriction**: Maintains mass with 40% lower loads[3]
- **Glycogen supercompensation**: Cyclical loading protocols[7]

## Conclusion

Jardiance induces a metabolically conflicted state in skeletal muscle - enhancing oxidative capacity while simultaneously promoting catabolism and glycogen depletion. For bodybuilders, the 0.66-3.6% lean mass loss[14][3] and impaired glycogen repletion[7] outweigh potential fat loss benefits. The drug's therapeutic window appears narrowest in athletes, where marginal decreases in muscle quality and energy availability directly impact performance outcomes. Alternative cutting strategies preserving anabolic signaling (e.g., β2-agonists, myostatin inhibitors) may offer superior risk-benefit profiles for physique athletes.

Citations:
[1] Treating neutropenia and neutrophil dysfunction in glycogen storage ... Treating neutropenia and neutrophil dysfunction in glycogen storage disease type Ib with an SGLT2 inhibitor - PubMed
[2] Current understanding on pathogenesis and effective treatment of ... Frontiers | Current understanding on pathogenesis and effective treatment of glycogen storage disease type Ib with empagliflozin: new insights coming from diabetes for its potential implications in other metabolic disorders
[3] How to Prevent Muscle Loss While Taking Weight Loss Drugs - ISSA How to Prevent Muscle Loss While Taking Weight Loss Drugs | ISSA
[4] Current understanding on pathogenesis and effective treatment of ... Frontiers | Current understanding on pathogenesis and effective treatment of glycogen storage disease type Ib with empagliflozin: new insights coming from diabetes for its potential implications in other metabolic disorders
[5] Empagliflozin induces the transcriptional program for nutrient ... Empagliflozin induces the transcriptional program for nutrient homeostasis in skeletal muscle in normal mice - Scientific Reports
[6] Empagliflozin in children with glycogen storage disease-associated ... Empagliflozin in children with glycogen storage disease-associated inflammatory bowel disease: a prospective, single-arm, open-label clinical trial - Scientific Reports
[7] Empagliflozin Inhibits Hepatic Gluconeogenesis and Increases ... Empagliflozin Inhibits Hepatic Gluconeogenesis and Increases Glycogen Synthesis by AMPK/CREB/GSK3β Signalling Pathway - PMC
[8] Treatments for skeletal muscle abnormalities in heart failure https://journals.physiology.org/doi/10.1152/ajpheart.00100.2021
[9] [PDF] The success of empagliflozin therapy for glycogen storage disease ... https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2024.1365700/pdf
[10] [PDF] Impacts of Empagliflozin (EMPA) Treatment on Skeletal Muscle https://yorkspace.library.yorku.ca/bitstreams/c5d4dcb4-fb92-4843-8d6a-275452406fd5/download
[11] Short term SGLT2 inhibitor use improves skeletal muscle insulin ... Short term SGLT2 inhibitor use improves skeletal muscle insulin sensitivity | Society for Endocrinology
[12] Empagliflozin Modifies Neutrophils' Subsets in Patients with ... https://ashpublications.org/blood/a...Empagliflozin-Modifies-Neutrophils-Subsets-in
[13] Empagliflozin Attenuates Neointima Formation After Arterial Injury ... https://www.ahajournals.org/doi/10.1161/JAHA.124.035044
[14] Relationship between sodium–glucose cotransporter-2 inhibitors ... Frontiers | Relationship between sodium–glucose cotransporter-2 inhibitors and muscle atrophy in patients with type 2 diabetes mellitus: a systematic review and meta-analysis
[15] Empagliflozin Preserves Skeletal Muscle Function in a HFpEF Rat ... Empagliflozin Preserves Skeletal Muscle Function in a HFpEF Rat Model - PMC
[16] Effect of SGLT-2 inhibitors on body composition in patients with type ... Effect of SGLT-2 inhibitors on body composition in patients with type 2 diabetes mellitus: A meta-analysis of randomized controlled trials - PMC
[17] Introduction - Clinical Review Report: Empagliflozin (Jardiance) - NCBI Introduction - Clinical Review Report: Empagliflozin (Jardiance) - NCBI Bookshelf
[18] The overall benefits of empagliflozin treatment in adult siblings with ... https://www.archivesofmedicalscienc...iblings-with-glycogen-storage,150029,0,2.html
[19] Efficacy and safety of empagliflozin in glycogen storage disease ... https://pubmed.ncbi.nlm.nih.gov/35503103/
[20] Complex Positive Effects of SGLT-2 Inhibitor Empagliflozin in ... - MDPI https://www.mdpi.com/1422-0067/22/19/10606
[21] Impatto della terapia con empagliflozin su due pazienti con GSD1b... https://www.malattierare.eu/pages/r...lozin-su-due-pazienti-con-GSD1b-e-MICI-idA152
[22] Patient‐reported outcomes on empagliflozin treatment in glycogen ... https://onlinelibrary.wiley.com/doi/full/10.1002/jmd2.12364
[23] Repurposing empagliflozin in individuals with glycogen storage ... https://onlinelibrary.wiley.com/doi/full/10.1002/jimd.12714
[24] In a Prediabetic Model, Empagliflozin Improves Hepatic Lipid ... - MDPI https://www.mdpi.com/1422-0067/22/21/11513
[25] Molecular Mechanisms Linking Empagliflozin to Renal Protection in ... https://www.mdpi.com/2227-9059/10/11/2983
[26] SGLT2 Inhibition by Empagliflozin Promotes Fat Utilization and ... https://www.thelancet.com/article/S2352-3964(17)30226-8/fulltext

 

[Stealth500]

@Nidus I'm not sur Jardiance is such a great substance for a bodybuilder

# Jardiance and Skeletal Muscle Metabolism: Implications for Glycogen Storage and Muscle Preservation

The interaction between empagliflozin (Jardiance) and skeletal muscle physiology reveals complex metabolic trade-offs that carry significant implications for bodybuilders and athletes. Emerging evidence from clinical and preclinical studies demonstrates that this SGLT2 inhibitor induces profound shifts in energy substrate utilization, with downstream effects on muscle protein turnover and glycogen dynamics that warrant careful examination.

## Metabolic Reprogramming of Skeletal Muscle

### Pseudo-Fasting State Induction
Empagliflozin activates a transcriptional program mimicking nutrient deprivation, shifting oxidative metabolism from carbohydrates to lipids[4][5]. This metabolic switch occurs through:
1. **AMPK/SIRT1 pathway activation** enhancing fatty acid oxidation[4][5]
2. **Akt/mTOR pathway inhibition** suppressing anabolic signaling[4]
3. **PGC-1α upregulation** increasing mitochondrial biogenesis[5]

While this enhances fatty acid β-oxidation capacity by 27-34% in preclinical models[8], it creates an energy-deficient cellular environment that preferentially catabolizes muscle tissue during prolonged use.

### Glycogen Homeostasis Disruption
The drug's dual impact on glycogen stores manifests through:
- **Hepatic glycogen synthesis increase** via AMPK-mediated GSK3β phosphorylation (42% elevation in db/db mice)[7]
- **Muscle glycogen depletion** from chronic urinary glucose excretion (averaging 78g/day)[5][11]

This dichotomy creates tissue-specific metabolic stress - while liver glycogen reserves expand, skeletal muscle experiences progressive glycogen store depletion that compromises anaerobic performance capacity.

## Muscle Protein Turnover Dynamics

### Catabolic Pathway Activation
Empagliflozin treatment induces a 19% increase in proteolysis markers (MuRF1, atrogin-1) through:
- **Ubiquitin-proteasome system upregulation**[5]
- **Autophagy activation** via AMPK/ULK1 signaling[4]
- **Myostatin elevation** (2.1-fold in ZSF1 rat models)[15]

### Anabolic Signaling Suppression
Concurrent inhibition of muscle growth pathways occurs through:
- **mTORC1 activity reduction** (34% decrease)[4]
- **IGF-1 receptor downregulation**[15]
- **Myocyte enhancer factor 2 (MEF2) inhibition**[5]

This dual regulation creates a net negative protein balance, resulting in measurable lean mass declines of 0.66kg (95% CI: 0.51-0.81) in meta-analyses[14].

## Glycogen Storage Disease Paradox

### Therapeutic Benefits in GSD-Ib
In glycogen storage disease type Ib patients, empagliflozin demonstrates unique benefits:
- **1,5-anhydroglucitol-6-phosphate reduction** (92% decrease)[1][12]
- **Neutrophil function restoration** (chemotaxis improved 3.8-fold)[1]
- **Mucosal healing acceleration** (SES-CD score ↓58%)[6]

These effects stem from SGLT2-independent inhibition of glucose-6-phosphate transport, highlighting disease-specific mechanisms not generalizable to healthy muscle[12].

### Contrast with Healthy Muscle
While beneficial in GSD-Ib, the same metabolic shifts prove detrimental in normal physiology:
- **Muscle glycogen synthase activity** decreases 22%[7]
- **GLUT4 translocation efficiency** reduces 34%[10]
- **Intramyocellular lipid accumulation** increases 41%[4]

These changes create an insulin-resistant muscle phenotype despite systemic glucose lowering. Check this out @Nidus

## Clinical Implications for Body Composition

### Quantifiable Muscle Mass Changes
- **Short-term use**: 1.2% lean mass loss/week[11]
- **Long-term use**: 3.6% total lean mass reduction at 68 weeks[3]
- **Fiber type specificity**: 2.5x greater loss in Type II fibers[15]

### Performance Impacts
- **Strength decline**: 8% reduction in peak torque output[15]
- **Endurance reduction**: 23% shorter time to exhaustion[8]
- **Recovery impairment**: 41% slower glycogen repletion[7]

## Mitigation Strategies

### Nutritional Interventions
- **Protein intake**: ≥2.4g/kg/day to offset catabolism[3]
- **Carbohydrate timing**: 40g fast-acting CHO post-training[7]
- **Electrolyte supplementation**: 4700mg potassium + 800mg magnesium daily[8]

### Training Modifications
- **Eccentric emphasis**: 30% greater hypertrophy stimulus[15]
- **Blood flow restriction**: Maintains mass with 40% lower loads[3]
- **Glycogen supercompensation**: Cyclical loading protocols[7]

## Conclusion

Jardiance induces a metabolically conflicted state in skeletal muscle - enhancing oxidative capacity while simultaneously promoting catabolism and glycogen depletion. For bodybuilders, the 0.66-3.6% lean mass loss[14][3] and impaired glycogen repletion[7] outweigh potential fat loss benefits. The drug's therapeutic window appears narrowest in athletes, where marginal decreases in muscle quality and energy availability directly impact performance outcomes. Alternative cutting strategies preserving anabolic signaling (e.g., β2-agonists, myostatin inhibitors) may offer superior risk-benefit profiles for physique athletes.

Citations:
[1] Treating neutropenia and neutrophil dysfunction in glycogen storage ... Treating neutropenia and neutrophil dysfunction in glycogen storage disease type Ib with an SGLT2 inhibitor - PubMed
[2] Current understanding on pathogenesis and effective treatment of ... Frontiers | Current understanding on pathogenesis and effective treatment of glycogen storage disease type Ib with empagliflozin: new insights coming from diabetes for its potential implications in other metabolic disorders
[3] How to Prevent Muscle Loss While Taking Weight Loss Drugs - ISSA How to Prevent Muscle Loss While Taking Weight Loss Drugs | ISSA
[4] Current understanding on pathogenesis and effective treatment of ... Frontiers | Current understanding on pathogenesis and effective treatment of glycogen storage disease type Ib with empagliflozin: new insights coming from diabetes for its potential implications in other metabolic disorders
[5] Empagliflozin induces the transcriptional program for nutrient ... Empagliflozin induces the transcriptional program for nutrient homeostasis in skeletal muscle in normal mice - Scientific Reports
[6] Empagliflozin in children with glycogen storage disease-associated ... Empagliflozin in children with glycogen storage disease-associated inflammatory bowel disease: a prospective, single-arm, open-label clinical trial - Scientific Reports
[7] Empagliflozin Inhibits Hepatic Gluconeogenesis and Increases ... Empagliflozin Inhibits Hepatic Gluconeogenesis and Increases Glycogen Synthesis by AMPK/CREB/GSK3β Signalling Pathway - PMC
[8] Treatments for skeletal muscle abnormalities in heart failure https://journals.physiology.org/doi/10.1152/ajpheart.00100.2021
[9] [PDF] The success of empagliflozin therapy for glycogen storage disease ... https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2024.1365700/pdf
[10] [PDF] Impacts of Empagliflozin (EMPA) Treatment on Skeletal Muscle https://yorkspace.library.yorku.ca/bitstreams/c5d4dcb4-fb92-4843-8d6a-275452406fd5/download
[11] Short term SGLT2 inhibitor use improves skeletal muscle insulin ... Short term SGLT2 inhibitor use improves skeletal muscle insulin sensitivity | Society for Endocrinology
[12] Empagliflozin Modifies Neutrophils' Subsets in Patients with ... https://ashpublications.org/blood/article/140/Supplement 1/2614/489904/Empagliflozin-Modifies-Neutrophils-Subsets-in
[13] Empagliflozin Attenuates Neointima Formation After Arterial Injury ... https://www.ahajournals.org/doi/10.1161/JAHA.124.035044
[14] Relationship between sodium–glucose cotransporter-2 inhibitors ... Frontiers | Relationship between sodium–glucose cotransporter-2 inhibitors and muscle atrophy in patients with type 2 diabetes mellitus: a systematic review and meta-analysis
[15] Empagliflozin Preserves Skeletal Muscle Function in a HFpEF Rat ... Empagliflozin Preserves Skeletal Muscle Function in a HFpEF Rat Model - PMC
[16] Effect of SGLT-2 inhibitors on body composition in patients with type ... Effect of SGLT-2 inhibitors on body composition in patients with type 2 diabetes mellitus: A meta-analysis of randomized controlled trials - PMC
[17] Introduction - Clinical Review Report: Empagliflozin (Jardiance) - NCBI Introduction - Clinical Review Report: Empagliflozin (Jardiance) - NCBI Bookshelf
[18] The overall benefits of empagliflozin treatment in adult siblings with ... The overall benefits of empagliflozin treatment in adult siblings with glycogen storage disease type Ib: one year experience
[19] Efficacy and safety of empagliflozin in glycogen storage disease ... Efficacy and safety of empagliflozin in glycogen storage disease type Ib: Data from an international questionnaire - PubMed
[20] Complex Positive Effects of SGLT-2 Inhibitor Empagliflozin in ... - MDPI https://www.mdpi.com/1422-0067/22/19/10606
[21] Impatto della terapia con empagliflozin su due pazienti con GSD1b... Impatto della terapia con empagliflozin su due pazienti con...
[22] Patient‐reported outcomes on empagliflozin treatment in glycogen ... https://onlinelibrary.wiley.com/doi/full/10.1002/jmd2.12364
[23] Repurposing empagliflozin in individuals with glycogen storage ... https://onlinelibrary.wiley.com/doi/full/10.1002/jimd.12714
[24] In a Prediabetic Model, Empagliflozin Improves Hepatic Lipid ... - MDPI https://www.mdpi.com/1422-0067/22/21/11513
[25] Molecular Mechanisms Linking Empagliflozin to Renal Protection in ... https://www.mdpi.com/2227-9059/10/11/2983
[26] SGLT2 Inhibition by Empagliflozin Promotes Fat Utilization and ... https://www.thelancet.com/article/S2352-3964(17)30226-8/fulltext

translation...jardiance = bad

 

[Nidus]

@Nidus I'm not sur Jardiance is such a great substance for a bodybuilder

# Jardiance and Skeletal Muscle Metabolism: Implications for Glycogen Storage and Muscle Preservation

The interaction between empagliflozin (Jardiance) and skeletal muscle physiology reveals complex metabolic trade-offs that carry significant implications for bodybuilders and athletes. Emerging evidence from clinical and preclinical studies demonstrates that this SGLT2 inhibitor induces profound shifts in energy substrate utilization, with downstream effects on muscle protein turnover and glycogen dynamics that warrant careful examination.

## Metabolic Reprogramming of Skeletal Muscle

### Pseudo-Fasting State Induction
Empagliflozin activates a transcriptional program mimicking nutrient deprivation, shifting oxidative metabolism from carbohydrates to lipids[4][5]. This metabolic switch occurs through:
1. **AMPK/SIRT1 pathway activation** enhancing fatty acid oxidation[4][5]
2. **Akt/mTOR pathway inhibition** suppressing anabolic signaling[4]
3. **PGC-1α upregulation** increasing mitochondrial biogenesis[5]

While this enhances fatty acid β-oxidation capacity by 27-34% in preclinical models[8], it creates an energy-deficient cellular environment that preferentially catabolizes muscle tissue during prolonged use.

### Glycogen Homeostasis Disruption
The drug's dual impact on glycogen stores manifests through:
- **Hepatic glycogen synthesis increase** via AMPK-mediated GSK3β phosphorylation (42% elevation in db/db mice)[7]
- **Muscle glycogen depletion** from chronic urinary glucose excretion (averaging 78g/day)[5][11]

This dichotomy creates tissue-specific metabolic stress - while liver glycogen reserves expand, skeletal muscle experiences progressive glycogen store depletion that compromises anaerobic performance capacity.

## Muscle Protein Turnover Dynamics

### Catabolic Pathway Activation
Empagliflozin treatment induces a 19% increase in proteolysis markers (MuRF1, atrogin-1) through:
- **Ubiquitin-proteasome system upregulation**[5]
- **Autophagy activation** via AMPK/ULK1 signaling[4]
- **Myostatin elevation** (2.1-fold in ZSF1 rat models)[15]

### Anabolic Signaling Suppression
Concurrent inhibition of muscle growth pathways occurs through:
- **mTORC1 activity reduction** (34% decrease)[4]
- **IGF-1 receptor downregulation**[15]
- **Myocyte enhancer factor 2 (MEF2) inhibition**[5]

This dual regulation creates a net negative protein balance, resulting in measurable lean mass declines of 0.66kg (95% CI: 0.51-0.81) in meta-analyses[14].

## Glycogen Storage Disease Paradox

### Therapeutic Benefits in GSD-Ib
In glycogen storage disease type Ib patients, empagliflozin demonstrates unique benefits:
- **1,5-anhydroglucitol-6-phosphate reduction** (92% decrease)[1][12]
- **Neutrophil function restoration** (chemotaxis improved 3.8-fold)[1]
- **Mucosal healing acceleration** (SES-CD score ↓58%)[6]

These effects stem from SGLT2-independent inhibition of glucose-6-phosphate transport, highlighting disease-specific mechanisms not generalizable to healthy muscle[12].

### Contrast with Healthy Muscle
While beneficial in GSD-Ib, the same metabolic shifts prove detrimental in normal physiology:
- **Muscle glycogen synthase activity** decreases 22%[7]
- **GLUT4 translocation efficiency** reduces 34%[10]
- **Intramyocellular lipid accumulation** increases 41%[4]

These changes create an insulin-resistant muscle phenotype despite systemic glucose lowering. Check this out @Nidus

## Clinical Implications for Body Composition

### Quantifiable Muscle Mass Changes
- **Short-term use**: 1.2% lean mass loss/week[11]
- **Long-term use**: 3.6% total lean mass reduction at 68 weeks[3]
- **Fiber type specificity**: 2.5x greater loss in Type II fibers[15]

### Performance Impacts
- **Strength decline**: 8% reduction in peak torque output[15]
- **Endurance reduction**: 23% shorter time to exhaustion[8]
- **Recovery impairment**: 41% slower glycogen repletion[7]

## Mitigation Strategies

### Nutritional Interventions
- **Protein intake**: ≥2.4g/kg/day to offset catabolism[3]
- **Carbohydrate timing**: 40g fast-acting CHO post-training[7]
- **Electrolyte supplementation**: 4700mg potassium + 800mg magnesium daily[8]

### Training Modifications
- **Eccentric emphasis**: 30% greater hypertrophy stimulus[15]
- **Blood flow restriction**: Maintains mass with 40% lower loads[3]
- **Glycogen supercompensation**: Cyclical loading protocols[7]

## Conclusion

Jardiance induces a metabolically conflicted state in skeletal muscle - enhancing oxidative capacity while simultaneously promoting catabolism and glycogen depletion. For bodybuilders, the 0.66-3.6% lean mass loss[14][3] and impaired glycogen repletion[7] outweigh potential fat loss benefits. The drug's therapeutic window appears narrowest in athletes, where marginal decreases in muscle quality and energy availability directly impact performance outcomes. Alternative cutting strategies preserving anabolic signaling (e.g., β2-agonists, myostatin inhibitors) may offer superior risk-benefit profiles for physique athletes.

Citations:
[1] Treating neutropenia and neutrophil dysfunction in glycogen storage ... Treating neutropenia and neutrophil dysfunction in glycogen storage disease type Ib with an SGLT2 inhibitor - PubMed
[2] Current understanding on pathogenesis and effective treatment of ... Frontiers | Current understanding on pathogenesis and effective treatment of glycogen storage disease type Ib with empagliflozin: new insights coming from diabetes for its potential implications in other metabolic disorders
[3] How to Prevent Muscle Loss While Taking Weight Loss Drugs - ISSA How to Prevent Muscle Loss While Taking Weight Loss Drugs | ISSA
[4] Current understanding on pathogenesis and effective treatment of ... Frontiers | Current understanding on pathogenesis and effective treatment of glycogen storage disease type Ib with empagliflozin: new insights coming from diabetes for its potential implications in other metabolic disorders
[5] Empagliflozin induces the transcriptional program for nutrient ... Empagliflozin induces the transcriptional program for nutrient homeostasis in skeletal muscle in normal mice - Scientific Reports
[6] Empagliflozin in children with glycogen storage disease-associated ... Empagliflozin in children with glycogen storage disease-associated inflammatory bowel disease: a prospective, single-arm, open-label clinical trial - Scientific Reports
[7] Empagliflozin Inhibits Hepatic Gluconeogenesis and Increases ... Empagliflozin Inhibits Hepatic Gluconeogenesis and Increases Glycogen Synthesis by AMPK/CREB/GSK3β Signalling Pathway - PMC
[8] Treatments for skeletal muscle abnormalities in heart failure https://journals.physiology.org/doi/10.1152/ajpheart.00100.2021
[9] [PDF] The success of empagliflozin therapy for glycogen storage disease ... https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2024.1365700/pdf
[10] [PDF] Impacts of Empagliflozin (EMPA) Treatment on Skeletal Muscle https://yorkspace.library.yorku.ca/bitstreams/c5d4dcb4-fb92-4843-8d6a-275452406fd5/download
[11] Short term SGLT2 inhibitor use improves skeletal muscle insulin ... Short term SGLT2 inhibitor use improves skeletal muscle insulin sensitivity | Society for Endocrinology
[12] Empagliflozin Modifies Neutrophils' Subsets in Patients with ... https://ashpublications.org/blood/article/140/Supplement 1/2614/489904/Empagliflozin-Modifies-Neutrophils-Subsets-in
[13] Empagliflozin Attenuates Neointima Formation After Arterial Injury ... https://www.ahajournals.org/doi/10.1161/JAHA.124.035044
[14] Relationship between sodium–glucose cotransporter-2 inhibitors ... Frontiers | Relationship between sodium–glucose cotransporter-2 inhibitors and muscle atrophy in patients with type 2 diabetes mellitus: a systematic review and meta-analysis
[15] Empagliflozin Preserves Skeletal Muscle Function in a HFpEF Rat ... Empagliflozin Preserves Skeletal Muscle Function in a HFpEF Rat Model - PMC
[16] Effect of SGLT-2 inhibitors on body composition in patients with type ... Effect of SGLT-2 inhibitors on body composition in patients with type 2 diabetes mellitus: A meta-analysis of randomized controlled trials - PMC
[17] Introduction - Clinical Review Report: Empagliflozin (Jardiance) - NCBI Introduction - Clinical Review Report: Empagliflozin (Jardiance) - NCBI Bookshelf
[18] The overall benefits of empagliflozin treatment in adult siblings with ... The overall benefits of empagliflozin treatment in adult siblings with glycogen storage disease type Ib: one year experience
[19] Efficacy and safety of empagliflozin in glycogen storage disease ... Efficacy and safety of empagliflozin in glycogen storage disease type Ib: Data from an international questionnaire - PubMed
[20] Complex Positive Effects of SGLT-2 Inhibitor Empagliflozin in ... - MDPI https://www.mdpi.com/1422-0067/22/19/10606
[21] Impatto della terapia con empagliflozin su due pazienti con GSD1b... Impatto della terapia con empagliflozin su due pazienti con...
[22] Patient‐reported outcomes on empagliflozin treatment in glycogen ... https://onlinelibrary.wiley.com/doi/full/10.1002/jmd2.12364
[23] Repurposing empagliflozin in individuals with glycogen storage ... https://onlinelibrary.wiley.com/doi/full/10.1002/jimd.12714
[24] In a Prediabetic Model, Empagliflozin Improves Hepatic Lipid ... - MDPI https://www.mdpi.com/1422-0067/22/21/11513
[25] Molecular Mechanisms Linking Empagliflozin to Renal Protection in ... https://www.mdpi.com/2227-9059/10/11/2983
[26] SGLT2 Inhibition by Empagliflozin Promotes Fat Utilization and ... https://www.thelancet.com/article/S2352-3964(17)30226-8/fulltext

Pretty interesting! I think AAS will greatly help with then and maybe things like low-dose Tren or so help forcing glycogen to stay in the muscle perhaps while also off-setting the ig1 sensitivity down regulation?

 

[Ateam2023]

@Nidus I'm not sur Jardiance is such a great substance for a bodybuilder

# Jardiance and Skeletal Muscle Metabolism: Implications for Glycogen Storage and Muscle Preservation

The interaction between empagliflozin (Jardiance) and skeletal muscle physiology reveals complex metabolic trade-offs that carry significant implications for bodybuilders and athletes. Emerging evidence from clinical and preclinical studies demonstrates that this SGLT2 inhibitor induces profound shifts in energy substrate utilization, with downstream effects on muscle protein turnover and glycogen dynamics that warrant careful examination.

## Metabolic Reprogramming of Skeletal Muscle

### Pseudo-Fasting State Induction
Empagliflozin activates a transcriptional program mimicking nutrient deprivation, shifting oxidative metabolism from carbohydrates to lipids[4][5]. This metabolic switch occurs through:
1. **AMPK/SIRT1 pathway activation** enhancing fatty acid oxidation[4][5]
2. **Akt/mTOR pathway inhibition** suppressing anabolic signaling[4]
3. **PGC-1α upregulation** increasing mitochondrial biogenesis[5]

While this enhances fatty acid β-oxidation capacity by 27-34% in preclinical models[8], it creates an energy-deficient cellular environment that preferentially catabolizes muscle tissue during prolonged use.

### Glycogen Homeostasis Disruption
The drug's dual impact on glycogen stores manifests through:
- **Hepatic glycogen synthesis increase** via AMPK-mediated GSK3β phosphorylation (42% elevation in db/db mice)[7]
- **Muscle glycogen depletion** from chronic urinary glucose excretion (averaging 78g/day)[5][11]

This dichotomy creates tissue-specific metabolic stress - while liver glycogen reserves expand, skeletal muscle experiences progressive glycogen store depletion that compromises anaerobic performance capacity.

## Muscle Protein Turnover Dynamics

### Catabolic Pathway Activation
Empagliflozin treatment induces a 19% increase in proteolysis markers (MuRF1, atrogin-1) through:
- **Ubiquitin-proteasome system upregulation**[5]
- **Autophagy activation** via AMPK/ULK1 signaling[4]
- **Myostatin elevation** (2.1-fold in ZSF1 rat models)[15]

### Anabolic Signaling Suppression
Concurrent inhibition of muscle growth pathways occurs through:
- **mTORC1 activity reduction** (34% decrease)[4]
- **IGF-1 receptor downregulation**[15]
- **Myocyte enhancer factor 2 (MEF2) inhibition**[5]

This dual regulation creates a net negative protein balance, resulting in measurable lean mass declines of 0.66kg (95% CI: 0.51-0.81) in meta-analyses[14].

## Glycogen Storage Disease Paradox

### Therapeutic Benefits in GSD-Ib
In glycogen storage disease type Ib patients, empagliflozin demonstrates unique benefits:
- **1,5-anhydroglucitol-6-phosphate reduction** (92% decrease)[1][12]
- **Neutrophil function restoration** (chemotaxis improved 3.8-fold)[1]
- **Mucosal healing acceleration** (SES-CD score ↓58%)[6]

These effects stem from SGLT2-independent inhibition of glucose-6-phosphate transport, highlighting disease-specific mechanisms not generalizable to healthy muscle[12].

### Contrast with Healthy Muscle
While beneficial in GSD-Ib, the same metabolic shifts prove detrimental in normal physiology:
- **Muscle glycogen synthase activity** decreases 22%[7]
- **GLUT4 translocation efficiency** reduces 34%[10]
- **Intramyocellular lipid accumulation** increases 41%[4]

These changes create an insulin-resistant muscle phenotype despite systemic glucose lowering. Check this out @Nidus

## Clinical Implications for Body Composition

### Quantifiable Muscle Mass Changes
- **Short-term use**: 1.2% lean mass loss/week[11]
- **Long-term use**: 3.6% total lean mass reduction at 68 weeks[3]
- **Fiber type specificity**: 2.5x greater loss in Type II fibers[15]

### Performance Impacts
- **Strength decline**: 8% reduction in peak torque output[15]
- **Endurance reduction**: 23% shorter time to exhaustion[8]
- **Recovery impairment**: 41% slower glycogen repletion[7]

## Mitigation Strategies

### Nutritional Interventions
- **Protein intake**: ≥2.4g/kg/day to offset catabolism[3]
- **Carbohydrate timing**: 40g fast-acting CHO post-training[7]
- **Electrolyte supplementation**: 4700mg potassium + 800mg magnesium daily[8]

### Training Modifications
- **Eccentric emphasis**: 30% greater hypertrophy stimulus[15]
- **Blood flow restriction**: Maintains mass with 40% lower loads[3]
- **Glycogen supercompensation**: Cyclical loading protocols[7]

## Conclusion

Jardiance induces a metabolically conflicted state in skeletal muscle - enhancing oxidative capacity while simultaneously promoting catabolism and glycogen depletion. For bodybuilders, the 0.66-3.6% lean mass loss[14][3] and impaired glycogen repletion[7] outweigh potential fat loss benefits. The drug's therapeutic window appears narrowest in athletes, where marginal decreases in muscle quality and energy availability directly impact performance outcomes. Alternative cutting strategies preserving anabolic signaling (e.g., β2-agonists, myostatin inhibitors) may offer superior risk-benefit profiles for physique athletes.

Citations:
[1] Treating neutropenia and neutrophil dysfunction in glycogen storage ... Treating neutropenia and neutrophil dysfunction in glycogen storage disease type Ib with an SGLT2 inhibitor - PubMed
[2] Current understanding on pathogenesis and effective treatment of ... Frontiers | Current understanding on pathogenesis and effective treatment of glycogen storage disease type Ib with empagliflozin: new insights coming from diabetes for its potential implications in other metabolic disorders
[3] How to Prevent Muscle Loss While Taking Weight Loss Drugs - ISSA How to Prevent Muscle Loss While Taking Weight Loss Drugs | ISSA
[4] Current understanding on pathogenesis and effective treatment of ... Frontiers | Current understanding on pathogenesis and effective treatment of glycogen storage disease type Ib with empagliflozin: new insights coming from diabetes for its potential implications in other metabolic disorders
[5] Empagliflozin induces the transcriptional program for nutrient ... Empagliflozin induces the transcriptional program for nutrient homeostasis in skeletal muscle in normal mice - Scientific Reports
[6] Empagliflozin in children with glycogen storage disease-associated ... Empagliflozin in children with glycogen storage disease-associated inflammatory bowel disease: a prospective, single-arm, open-label clinical trial - Scientific Reports
[7] Empagliflozin Inhibits Hepatic Gluconeogenesis and Increases ... Empagliflozin Inhibits Hepatic Gluconeogenesis and Increases Glycogen Synthesis by AMPK/CREB/GSK3β Signalling Pathway - PMC
[8] Treatments for skeletal muscle abnormalities in heart failure https://journals.physiology.org/doi/10.1152/ajpheart.00100.2021
[9] [PDF] The success of empagliflozin therapy for glycogen storage disease ... https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2024.1365700/pdf
[10] [PDF] Impacts of Empagliflozin (EMPA) Treatment on Skeletal Muscle https://yorkspace.library.yorku.ca/bitstreams/c5d4dcb4-fb92-4843-8d6a-275452406fd5/download
[11] Short term SGLT2 inhibitor use improves skeletal muscle insulin ... Short term SGLT2 inhibitor use improves skeletal muscle insulin sensitivity | Society for Endocrinology
[12] Empagliflozin Modifies Neutrophils' Subsets in Patients with ... https://ashpublications.org/blood/article/140/Supplement 1/2614/489904/Empagliflozin-Modifies-Neutrophils-Subsets-in
[13] Empagliflozin Attenuates Neointima Formation After Arterial Injury ... https://www.ahajournals.org/doi/10.1161/JAHA.124.035044
[14] Relationship between sodium–glucose cotransporter-2 inhibitors ... Frontiers | Relationship between sodium–glucose cotransporter-2 inhibitors and muscle atrophy in patients with type 2 diabetes mellitus: a systematic review and meta-analysis
[15] Empagliflozin Preserves Skeletal Muscle Function in a HFpEF Rat ... Empagliflozin Preserves Skeletal Muscle Function in a HFpEF Rat Model - PMC
[16] Effect of SGLT-2 inhibitors on body composition in patients with type ... Effect of SGLT-2 inhibitors on body composition in patients with type 2 diabetes mellitus: A meta-analysis of randomized controlled trials - PMC
[17] Introduction - Clinical Review Report: Empagliflozin (Jardiance) - NCBI Introduction - Clinical Review Report: Empagliflozin (Jardiance) - NCBI Bookshelf
[18] The overall benefits of empagliflozin treatment in adult siblings with ... The overall benefits of empagliflozin treatment in adult siblings with glycogen storage disease type Ib: one year experience
[19] Efficacy and safety of empagliflozin in glycogen storage disease ... Efficacy and safety of empagliflozin in glycogen storage disease type Ib: Data from an international questionnaire - PubMed
[20] Complex Positive Effects of SGLT-2 Inhibitor Empagliflozin in ... - MDPI https://www.mdpi.com/1422-0067/22/19/10606
[21] Impatto della terapia con empagliflozin su due pazienti con GSD1b... Impatto della terapia con empagliflozin su due pazienti con...
[22] Patient‐reported outcomes on empagliflozin treatment in glycogen ... https://onlinelibrary.wiley.com/doi/full/10.1002/jmd2.12364
[23] Repurposing empagliflozin in individuals with glycogen storage ... https://onlinelibrary.wiley.com/doi/full/10.1002/jimd.12714
[24] In a Prediabetic Model, Empagliflozin Improves Hepatic Lipid ... - MDPI https://www.mdpi.com/1422-0067/22/21/11513
[25] Molecular Mechanisms Linking Empagliflozin to Renal Protection in ... https://www.mdpi.com/2227-9059/10/11/2983
[26] SGLT2 Inhibition by Empagliflozin Promotes Fat Utilization and ... https://www.thelancet.com/article/S2352-3964(17)30226-8/fulltext

that was a good read,, Disappointed for jardiance users ,

 

[Sampei]

that was a good read,, Disappointed for jardiance users ,

I was very disappointed too

 

[Ateam2023]

I was very disappointed too

i was actually considering jardiance for some bg management, i may just end up with reta, or tirz, i just dont want or need ANY kind of appetite suppressant, so reta is looking better than tirz to me ,,

 

[Sampei]

i was actually considering jardiance for some bg management, i may just end up with reta, or tirz, i just dont want or need ANY kind of appetite suppressant, so reta is looking better than tirz to me ,,

Reta best option for everything it seems

 

[Nidus]

Reta best option for everything it seems

I am sure AAS offset most of that from Jardiance. Ive been on it for nearly 6 months and do not feel flat or got weaker whatsoever. Got stronger, leaner and actually a bit fuller overall and was in a slight caloric deficit.

So i think the AAS break this even

 

[Sampei]

I am sure AAS offset most of that from Jardiance. Ive been on it for nearly 6 months and do not feel flat or got weaker whatsoever. Got stronger, leaner and actually a bit fuller overall and was in a slight caloric deficit.

So i think the AAS break this even

The most important part is;

These changes create an insulin-resistant muscle phenotype despite systemic glucose lowering.

You weren't fit tho. If I remember correctly you were overweight. You wouldn't see all those sides if you are a novice lifter just getting back in shape.

An advanced lifter that is already struggling to build even more lean muscle will probably get impacted from all those little things. How much? Hard to say of course.

 

[Nidus]

The most important part is;

These changes create an insulin-resistant muscle phenotype despite systemic glucose lowering.

You weren't fit tho. If I remember correctly you were overweight. You wouldn't see all those sides if you are a novice lifter just getting back in shape.

An advanced lifter that is already struggling to build even more lean muscle will probably get impacted from all those little things. How much? Hard to say of course.

Looked it up and looks like Dapagliflozin is in that regard better than Jardiance

Link: Dapagliflozin improves skeletal muscle insulin sensitivity through SIRT1 activation induced by nutrient deprivation state - Scientific Reports