Tesarossa
𝓓𝓪𝔂𝓓𝓻𝓮𝓪𝓶𝓮𝓻
- Joined
- Jan 3, 2026
- Posts
- 10,937
- Reputation
- 26,799
All you iqlets loved the story style guide so heres another one.
Guide im referencing below
Every morning the scale showed the girl the same exact reading, maybe even worse than the day before. Every evening her reflection looked tired of the fight with her weight. Hunger wasn’t just physical anymore it was emotional, habitual, exhausting. The way she looked in the mirror basically told the story of the rest of her day. She wanted something that not only got rid of her insane hunger, but actually changed the
The first guy who showed up was Semaglutide .Their relationship wasn’t instant. It was slow, careful, respectful of her limits. Start low and Rise overtime. Consistent, Predictable. Once a week he showed up and did exactly what he promised, slowed everything in her body down, made her feel full sooner, took the erratic edge off her appetite. It worked, She lost weight. But there were nights when she still felt like she was fighting with her own metabolism instead of being met by it.
Semaglutide
Semaglutide is a long acting glucagon like peptide -1 (GLP-1) receptor agonist. It is the active ingredient in:
Ozempic (injectable) primarily for type 2 diabetes
Wegovy (injectable and oral tablet) primarily for chronic weight management and cardiovascular risk reduction
Rybelsus (oral tablet) for type 2 diabetes
It is structurally similar to human GLP-1 (94% homology) but modified with a fatty acid chain that allows albumin binding, giving it a half life of basically one week.
Mechanism of Action / Pathways
Semaglutide selectively binds to and activates the GLP-1 receptor. Key effects include:
Pancreas: Stimulates glucose dependent insulin secretion from beta cells and suppresses glucagon secretion from alpha cells (especially postprandially). This lowers blood glucose with a low intrinsic risk of hypoglycemia when used alone.
Stomach: Delays gastric emptying, which slows nutrient absorption and promotes earlier and prolonged feelings of fullness.
Brain: Acts on GLP-1 receptors in appetite regulating centers (including the hypothalamus and brainstem), reducing hunger, food intake, and “food noise”/cravings.
Overall metabolic effects: Leads to reduced caloric intake, preferential loss of fat mass over lean mass, improved glycemic control, and modest reductions in blood pressure and lipids. Cardiovascular risk reduction has been demonstrated, though the exact mechanism is not fully established and may involve weight loss plus direct vascular or anti inflammatory effects.
It does not significantly increase energy usage the way some multi agonists (e.g., those with glucagon activity) do.
Chronic weight management in adults with BMI >30 (or > 27 with at least one weight related health condition), used with diet and physical activity.
Reduction of major adverse cardiovascular events (cardiovascular death, nonfatal MI, nonfatal stroke) in adults with established CVD and obesity/overweight (SELECT trial data).
Additional emerging/approved uses in some regions include certain stages of metabolic dysfunction.
Dosage
Injectable (once weekly, subcutaneous — abdomen, thigh, or upper arm)
:Weeks 1-4 - Dose 0.5mg
:Weeks 5-8 - 0.5mg
:Weeks 9-12 - 1mg
Weeks 13- 16 - 1.7-2mg
Weight loss (STEP trials, 2.4 mg injectable): Average 15% body weight reduction at 68 weeks (vs 2–3% placebo) in people without diabetes. Higher proportions achieve >10%, >15%, and >20% loss compared with placebo.
Side Effects
Nausea (most frequent, up to 40–44% in weight loss trials), diarrhea, vomiting, constipation, abdominal pain, dyspepsia, bloating, eructation (burping), flatulence, GERD.
Headache, fatigue, dizziness, decreased appetite, hair loss ( related to weight loss), dysesthesia (altered skin sensation) in some reports.
Then Tirzepatide walked in , bolder ,pays her more attention. He not only calmed her hunger, he also rewired how her body handled energy. 2 things down , More complete. The scale moved wayyyy faster than she expected. Her clothes loosened in ways that felt surprising. Still, something in her sensed there was another layer waiting.
Tirzepatide
Tirzepatide is a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist (sometimes called a “twincretin”). It is the active ingredient in:
Mounjaro primarily for type 2 diabetes
Zepbound primarily for chronic weight management and moderate to severe obstructive sleep apnea (OSA) in adults with obesity
It is a single synthetic peptide engineered for once a week dosing via albumin binding, with a halflife of roughly five days.
Core Shared Signaling Pathway
Tirzepatide binds the extracellular domain and transmembrane core of the receptor.
The receptor undergoes a conformational change that recruits the heterotrimeric Gs protein.
Gαs exchanges GDP for GTP and activates adenylyl cyclase.
Adenylyl cyclase converts ATP → cyclic AMP (cAMP).
Elevated cAMP activates:
Protein kinase A (PKA)
Exchange protein activated by cAMP (Epac)
Mechanism of Action / Pathways
Tirzepatide activates both the GIP and GLP-1 receptors:
GLP 1 receptor effects: Stimulates glucose dependent insulin secretion, suppresses glucagon secretion (especially when glucose is elevated), slows gastric emptying, and reduces appetite via central nervous system pathways.
GIP receptor effects: Further enhances glucose dependent insulin secretion, improves insulin sensitivity, modulates adipose tissue metabolism, and appears to contribute additional effects on appetite regulation and energy balance. The dual action is believed to lie under the greater average weight loss compared with GLP-1 only agents.
Overall results: Improved glycemic control, largel reduction in caloric intake, l fat mass loss, and favorable effects on blood pressure, lipids, and (in some populations) heart failure outcomes.
Dosage
Start - 2.5mg - 4 weeks
Step 1 - 5mg - 4 weeks
Step 2 - 7.5mg - 4 weeks
Step 3 - 10mg - 4 weeks
Step 4 - 12.5 mg - 4 weeks
Maintaining - 15mg - Long as you desire
The 2.5 mg dose is for treatment initiation only and is not made to be a maintenance dose.
Increase in 2.5 mg increments after at least 4 weeks on the current dose, based on response and tolerability.
Recommended maintenance doses are typically 5 mg, 10 mg, or 15 mg once weekly (for OSA, often 10 mg or 15 mg).
Efficiency Highlights
Weight loss (SURMOUNT-1, people without diabetes): Mean reductions of approximately 15.0% (5 mg), 19.5% (10 mg), and 20.9% (15 mg) at 72 weeks versus 3% with placebo.
Side Effects
Nausea, diarrhea, vomiting, constipation, abdominal pain, dyspepsia, decreased appetite.
Other: Injection site reactions, fatigue, hypersensitivity reactions, hair loss (often related to rapid weight loss),heartburn
And then came Retatrutide.
He didn’t walk in extremely loud. He showed up and stayed. Three pathways at once appetite, metabolic flexibility, and genuine fat MELTING. He not only reduced what she took in, he also increased what her body was willing to let go of. Energy rose. Liver fat began to melt. The kind of weight loss that used to belong only to surgery started looking possible in her bedroom.
Their relationship wasn’t instant. It was slow, careful, respectful of her limits. Start low. Rise gradually. Let the nausea settle. Let the body adapt. Over months the transformation became undeniable. In the longest studies, people on the highest dose were losing close to 28 percent of their bodyfat. It wasnt punishing the body either it was like they made a handshake deal.
Retratrutide
Ret (also called “reta”) is an investigational triple hormone receptor agonist developed by Eli Lilly. It simultaneously activates the receptors for:
Glucose dependent insulinotropic polypeptide (GIP)
Glucagon like peptide-1 (GLP-1)
Glucagon
It is a single synthetic peptide.
Mechanism of Action / Pathways
Retatrutide’s triple agonism produces complementary effects:
GLP-1 receptor: Increases glucose dependent insulin secretion, suppresses glucagon (when glucose is high), slows gastric emptying, and reduces appetite via central nervous system pathways.
GIP receptor: Further enhances insulin secretion and sensitivity, modulates adipose tissue metabolism, and contributes to appetite and energy regulation.
Retatrutide binds the extracellular domain and transmembrane core of the receptor.
The receptor undergoes a conformational change that recruits the heterotrimeric Gs protein.
Gαs exchanges GDP for GTP and activates adenylyl cyclase.
Adenylyl cyclase converts ATP → cyclic AMP (cAMP).
Elevated cAMP activates:
Protein kinase A (PKA)
Exchange protein activated by cAMP (Epac)
Glucagon receptor (the differentiating feature): Increases energy expenditure, promotes hepatic fat oxidation and lipolysis, and helps mobilize stored fat. Partial agonism is designed to gain metabolic benefits while limiting hyperglycemia risk.
The result is reduced caloric intake plus increased caloric burn and preferential fat mobilization (including substantial reductions in liver fat in earlier studies). This dual sided action on energy balance makes it different from dual GIP/GLP-1 agonists such as tirzepatide and single GLP-1 agonists such as semaglutide.
Relative Potency
GIPR: highest potency (EC50 - 0.06 nM) — more potent than native GIP
GLP-1R: intermediate (EC50 - 0.78 nM) — somewhat less potent than native GLP-1
GCGR: lower but pharmacologically relevant (EC50 - 5.8 nM) — partial relative to native glucagon
Dosage
Target 4 mg: 2 mg → 4 mg 20 weeks
Target 9 mg: 2 mg → 4 mg → 6 mg → 9 mg up to 40 weeks
Target 12 mg: 2 mg → 4 mg → 6 mg → 9 mg → 12 mg off and on consistently
Side Effects
Nausea
Diarrhea
Vomiting
Constipation
Decreased appetite
Abdominal discomfort
Wraps the guide up
yk the drill
@Ponyville @j1gga @Regret @xye @RandomAutist
Guide im referencing below
Thread Song
Every morning the scale showed the girl the same exact reading, maybe even worse than the day before. Every evening her reflection looked tired of the fight with her weight. Hunger wasn’t just physical anymore it was emotional, habitual, exhausting. The way she looked in the mirror basically told the story of the rest of her day. She wanted something that not only got rid of her insane hunger, but actually changed the
The first guy who showed up was Semaglutide .Their relationship wasn’t instant. It was slow, careful, respectful of her limits. Start low and Rise overtime. Consistent, Predictable. Once a week he showed up and did exactly what he promised, slowed everything in her body down, made her feel full sooner, took the erratic edge off her appetite. It worked, She lost weight. But there were nights when she still felt like she was fighting with her own metabolism instead of being met by it.
Semaglutide
Semaglutide is a long acting glucagon like peptide -1 (GLP-1) receptor agonist. It is the active ingredient in:
Ozempic (injectable) primarily for type 2 diabetes
Wegovy (injectable and oral tablet) primarily for chronic weight management and cardiovascular risk reduction
Rybelsus (oral tablet) for type 2 diabetes
It is structurally similar to human GLP-1 (94% homology) but modified with a fatty acid chain that allows albumin binding, giving it a half life of basically one week.
Mechanism of Action / Pathways
Semaglutide selectively binds to and activates the GLP-1 receptor. Key effects include:
Pancreas: Stimulates glucose dependent insulin secretion from beta cells and suppresses glucagon secretion from alpha cells (especially postprandially). This lowers blood glucose with a low intrinsic risk of hypoglycemia when used alone.
Stomach: Delays gastric emptying, which slows nutrient absorption and promotes earlier and prolonged feelings of fullness.
Brain: Acts on GLP-1 receptors in appetite regulating centers (including the hypothalamus and brainstem), reducing hunger, food intake, and “food noise”/cravings.
Overall metabolic effects: Leads to reduced caloric intake, preferential loss of fat mass over lean mass, improved glycemic control, and modest reductions in blood pressure and lipids. Cardiovascular risk reduction has been demonstrated, though the exact mechanism is not fully established and may involve weight loss plus direct vascular or anti inflammatory effects.
It does not significantly increase energy usage the way some multi agonists (e.g., those with glucagon activity) do.
Chronic weight management in adults with BMI >30 (or > 27 with at least one weight related health condition), used with diet and physical activity.
Reduction of major adverse cardiovascular events (cardiovascular death, nonfatal MI, nonfatal stroke) in adults with established CVD and obesity/overweight (SELECT trial data).
Additional emerging/approved uses in some regions include certain stages of metabolic dysfunction.
Dosage
Injectable (once weekly, subcutaneous — abdomen, thigh, or upper arm)
:Weeks 1-4 - Dose 0.5mg
:Weeks 5-8 - 0.5mg
:Weeks 9-12 - 1mg
Weeks 13- 16 - 1.7-2mg
Weight loss (STEP trials, 2.4 mg injectable): Average 15% body weight reduction at 68 weeks (vs 2–3% placebo) in people without diabetes. Higher proportions achieve >10%, >15%, and >20% loss compared with placebo.
Side Effects
Nausea (most frequent, up to 40–44% in weight loss trials), diarrhea, vomiting, constipation, abdominal pain, dyspepsia, bloating, eructation (burping), flatulence, GERD.
Headache, fatigue, dizziness, decreased appetite, hair loss ( related to weight loss), dysesthesia (altered skin sensation) in some reports.
Then Tirzepatide walked in , bolder ,pays her more attention. He not only calmed her hunger, he also rewired how her body handled energy. 2 things down , More complete. The scale moved wayyyy faster than she expected. Her clothes loosened in ways that felt surprising. Still, something in her sensed there was another layer waiting.
Tirzepatide
Tirzepatide is a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist (sometimes called a “twincretin”). It is the active ingredient in:
Mounjaro primarily for type 2 diabetes
Zepbound primarily for chronic weight management and moderate to severe obstructive sleep apnea (OSA) in adults with obesity
It is a single synthetic peptide engineered for once a week dosing via albumin binding, with a halflife of roughly five days.
Core Shared Signaling Pathway
Tirzepatide binds the extracellular domain and transmembrane core of the receptor.
The receptor undergoes a conformational change that recruits the heterotrimeric Gs protein.
Gαs exchanges GDP for GTP and activates adenylyl cyclase.
Adenylyl cyclase converts ATP → cyclic AMP (cAMP).
Elevated cAMP activates:
Protein kinase A (PKA)
Exchange protein activated by cAMP (Epac)
Mechanism of Action / Pathways
Tirzepatide activates both the GIP and GLP-1 receptors:
GLP 1 receptor effects: Stimulates glucose dependent insulin secretion, suppresses glucagon secretion (especially when glucose is elevated), slows gastric emptying, and reduces appetite via central nervous system pathways.
GIP receptor effects: Further enhances glucose dependent insulin secretion, improves insulin sensitivity, modulates adipose tissue metabolism, and appears to contribute additional effects on appetite regulation and energy balance. The dual action is believed to lie under the greater average weight loss compared with GLP-1 only agents.
Overall results: Improved glycemic control, largel reduction in caloric intake, l fat mass loss, and favorable effects on blood pressure, lipids, and (in some populations) heart failure outcomes.
Dosage
Start - 2.5mg - 4 weeks
Step 1 - 5mg - 4 weeks
Step 2 - 7.5mg - 4 weeks
Step 3 - 10mg - 4 weeks
Step 4 - 12.5 mg - 4 weeks
Maintaining - 15mg - Long as you desire
The 2.5 mg dose is for treatment initiation only and is not made to be a maintenance dose.
Increase in 2.5 mg increments after at least 4 weeks on the current dose, based on response and tolerability.
Recommended maintenance doses are typically 5 mg, 10 mg, or 15 mg once weekly (for OSA, often 10 mg or 15 mg).
Efficiency Highlights
Weight loss (SURMOUNT-1, people without diabetes): Mean reductions of approximately 15.0% (5 mg), 19.5% (10 mg), and 20.9% (15 mg) at 72 weeks versus 3% with placebo.
Side Effects
Nausea, diarrhea, vomiting, constipation, abdominal pain, dyspepsia, decreased appetite.
Other: Injection site reactions, fatigue, hypersensitivity reactions, hair loss (often related to rapid weight loss),heartburn
And then came Retatrutide.
He didn’t walk in extremely loud. He showed up and stayed. Three pathways at once appetite, metabolic flexibility, and genuine fat MELTING. He not only reduced what she took in, he also increased what her body was willing to let go of. Energy rose. Liver fat began to melt. The kind of weight loss that used to belong only to surgery started looking possible in her bedroom.
Their relationship wasn’t instant. It was slow, careful, respectful of her limits. Start low. Rise gradually. Let the nausea settle. Let the body adapt. Over months the transformation became undeniable. In the longest studies, people on the highest dose were losing close to 28 percent of their bodyfat. It wasnt punishing the body either it was like they made a handshake deal.
Retratrutide
Ret (also called “reta”) is an investigational triple hormone receptor agonist developed by Eli Lilly. It simultaneously activates the receptors for:
Glucose dependent insulinotropic polypeptide (GIP)
Glucagon like peptide-1 (GLP-1)
Glucagon
It is a single synthetic peptide.
Mechanism of Action / Pathways
Retatrutide’s triple agonism produces complementary effects:
GLP-1 receptor: Increases glucose dependent insulin secretion, suppresses glucagon (when glucose is high), slows gastric emptying, and reduces appetite via central nervous system pathways.
GIP receptor: Further enhances insulin secretion and sensitivity, modulates adipose tissue metabolism, and contributes to appetite and energy regulation.
Retatrutide binds the extracellular domain and transmembrane core of the receptor.
The receptor undergoes a conformational change that recruits the heterotrimeric Gs protein.
Gαs exchanges GDP for GTP and activates adenylyl cyclase.
Adenylyl cyclase converts ATP → cyclic AMP (cAMP).
Elevated cAMP activates:
Protein kinase A (PKA)
Exchange protein activated by cAMP (Epac)
Glucagon receptor (the differentiating feature): Increases energy expenditure, promotes hepatic fat oxidation and lipolysis, and helps mobilize stored fat. Partial agonism is designed to gain metabolic benefits while limiting hyperglycemia risk.
The result is reduced caloric intake plus increased caloric burn and preferential fat mobilization (including substantial reductions in liver fat in earlier studies). This dual sided action on energy balance makes it different from dual GIP/GLP-1 agonists such as tirzepatide and single GLP-1 agonists such as semaglutide.
Relative Potency
GIPR: highest potency (EC50 - 0.06 nM) — more potent than native GIP
GLP-1R: intermediate (EC50 - 0.78 nM) — somewhat less potent than native GLP-1
GCGR: lower but pharmacologically relevant (EC50 - 5.8 nM) — partial relative to native glucagon
Dosage
Target 4 mg: 2 mg → 4 mg 20 weeks
Target 9 mg: 2 mg → 4 mg → 6 mg → 9 mg up to 40 weeks
Target 12 mg: 2 mg → 4 mg → 6 mg → 9 mg → 12 mg off and on consistently
Side Effects
Nausea
Diarrhea
Vomiting
Constipation
Decreased appetite
Abdominal discomfort
Wraps the guide up
yk the drill
@Ponyville @j1gga @Regret @xye @RandomAutist
Last edited:
