Fat Loss

“Landmark study identified MOTS-c as a novel 16-amino-acid mitochondrial-derived peptide encoded within the mitochondrial 12S rRNA gene. MOTS-c was observed to regulate metabolic homeostasis through AMPK activation by inhibiting the folate cycle and de novo purine biosynthesis pathway. In mouse models, MOTS-c administration prevented age-dependent and high-fat-diet-induced insulin resistance and reduced diet-induced obesity. The primary target organ was identified as skeletal muscle. This was the first report of a mitochondrial-encoded peptide functioning as a systemic metabolic regulator.”

“Peter Attia discussed MOTS-c on The Drive podcast in the context of mitochondrial efficiency and age-related metabolic decline. He described it as a mitochondrial-derived peptide that acts as an endogenous signaling molecule regulating metabolic homeostasis through AMPK-dependent pathways. Attia noted the preclinical data from Lee et al. (2015) showing MOTS-c prevented diet-induced obesity and reversed age-dependent insulin resistance in mice, but emphasized the lack of controlled human clinical trial data.”

“12-week MOTS-c cycle at 10mg 2x/week. Primary interest was insulin sensitivity and metabolic regulation. Female, early 40s, prediabetic range. HbA1c went from 5.8 to 5.5 over the cycle. Noticed better post-meal blood sugar readings on my CGM by week 4. Energy levels improved gradually. The research on MOTS-c as a mitochondrial-derived peptide with exercise mimetic properties is what drew me to it — all preclinical data so far but the metabolic pathway modulation is well-characterized.”

Cycle: 12 weeks

“Ran MOTS-c at 5mg 3x/week for 8 weeks targeting metabolic function and fat loss. Had mild flu-like symptoms the first 4-5 days that resolved. By week 3 I noticed improved exercise capacity — could push harder on HIIT sessions without the same level of fatigue. Lost about 4 lbs of body fat over 8 weeks while maintaining muscle mass per DEXA scan. Fasting glucose dropped from 98 to 89 mg/dL. This peptide acts as an exercise mimetic through AMPK activation and metabolic signaling.”

Cycle: 8 weeks

“Preclinical study examining 5-amino-1MQ as an NNMT inhibitor. In diet-induced obese mouse models, the compound was associated with reduced body weight, decreased adipose tissue mass, and smaller adipocyte size without changes in food intake. The authors noted increased cellular NAD+ and SAM levels, describing a mechanism of enhanced energy expenditure.”

“Paired 5-Amino with a caloric deficit and noticed more consistent energy throughout the day. Lost 5 lbs in 8 weeks. Felt like recovery from workouts was slightly better. Still gathering data on this one — there's almost no long-term anecdotal info out there yet.”

Cycle: 8 weeks

“Only ran this for 6 weeks so far. Down about 3 lbs. Felt like my metabolism was slightly elevated — running warmer and more energy. Not much community data to compare to. The NNMT inhibition mechanism is interesting but this is still very new territory.”

Cycle: 6 weeks

“Very early adopter here. Ran 5-Amino for 8 weeks at 100mg/day split into two doses. Lost about 6 lbs and noticed increased energy during workouts. Hard to find much info or other people running this compound yet. Tolerated it well overall.”

Cycle: 8 weeks

“Randomized controlled trial of berberine (1500 mg/day) in obese subjects over 12 weeks. Berberine administration was associated with a reduction in body weight (-2.3 kg vs placebo) and improvement in insulin sensitivity markers. The study noted improvements in triglycerides and total cholesterol.”

Cycle: 12 weeks

“Systematic review and meta-analysis of 12 RCTs (n=1,160). Berberine supplementation was associated with a significant reduction in body weight (WMD: -2.07 kg), BMI (WMD: -0.47 kg/m2), and waist circumference compared to placebo. GI adverse events were the most commonly reported side effects.”

“Dr. Mark Hyman discussed berberine as a plant alkaloid with reported associations to blood sugar regulation and metabolic health. He noted that some research has described berberine's impact on AMPK activation as comparable to mechanisms observed in metformin.”

“Ran berberine at a higher dose for 16 weeks. Dropped 14 lbs and A1c went from 5.9 to 5.4. The diarrhea at full dose was rough — had to split doses across meals. Felt like blood sugar regulation was the main mechanism. Would describe the weight loss as a secondary benefit.”

Cycle: 16 weeks

“Tried berberine after seeing the 'nature's Ozempic' posts everywhere. Lost about 5 lbs in 8 weeks which was fine but nowhere near what people online described. Blood sugar felt more stable and I had fewer carb cravings. The low energy in the afternoons was annoying.”

Cycle: 8 weeks

“The GI side effects were brutal for the first 2 weeks — almost quit. Started taking it with meals and it got much better. Lost about 9 lbs over 12 weeks. Fasting blood glucose dropped noticeably. Not dramatic fat loss but steady.”

Cycle: 12 weeks

“Comprehensive review of tesamorelin pharmacology and clinical data. The compound was noted to produce sustained reductions in visceral adipose tissue over 52 weeks in HIV-associated lipodystrophy, with reported improvements in trunk fat, lipid profiles, and patient-reported body image.”

Cycle: 52 weeks

“Randomized, double-blind, placebo-controlled trial in HIV-infected patients with lipodystrophy. Tesamorelin administration was associated with a significant reduction in trunk fat (-15.2%) compared to placebo over 26 weeks, as measured by CT scan.”

Cycle: 26 weeks

“Dr. Andrew Huberman discussed tesamorelin on his podcast as a GHRH analog that has been noted to increase growth hormone secretion and has been associated with reductions in visceral adipose tissue in clinical populations.”

“Used tesamorelin primarily for the sleep and GH-boosting benefits but was pleasantly surprised by the fat loss. Lost about 8 lbs and the midsection visibly tightened. Sleep was noticeably deeper within the first week.”

Cycle: 12 weeks

“Body recomposition was the main benefit — lost belly fat while maintaining muscle. DEXA scan showed a 14% reduction in trunk fat over 16 weeks. The increased appetite was unexpected and made dieting harder, but the results were still meaningful.”

Cycle: 16 weeks

“Noticeable reduction in visceral fat around week 6. Waist measurement dropped 2 inches over 12 weeks. Sleep quality improved significantly — deeper and more restorative. Felt like body composition shifted even though scale weight only changed 6 lbs.”

Cycle: 12 weeks

“Phase IIb clinical trial of oral AOD-9604 in obese subjects. The study reported that the HGH fragment 176-191 (AOD-9604) was associated with a reduction in body weight compared to placebo, with a favorable tolerability profile noted across dose groups.”

Cycle: 12 weeks

“Dr. Seeds discussed AOD-9604 as a fragment of human growth hormone (amino acids 176-191) and described its use in clinical settings for body composition, noting that it has been reported to act on fat tissue without the broader hormonal impact associated with full HGH.”

“Moderate fat loss noted around weeks 6-10, primarily in the abdominal area. The compound appeared well-tolerated but the results were underwhelming compared to expectations. Down about 5 lbs but also increased step count.”

Cycle: 12 weeks

“I noticed a gradual reduction in stubborn lower belly fat over 16 weeks — about 7 lbs total. No appetite changes, no energy changes. Very mild compound. Paired it with fasted cardio which may have contributed.”

Cycle: 16 weeks

“Ran AOD for 8 weeks and honestly noticed almost nothing. Injection sites were irritated constantly. Switched to a different protocol after. Disappointed given the hype in peptide forums.”

Cycle: 8 weeks

“Subtle changes around the midsection by week 8 but nothing dramatic. Lost about 4 lbs total. Hard to tell if it was the AOD or the fact that I cleaned up my diet at the same time.”

Cycle: 12 weeks

“The PIONEER 1 trial reported that oral semaglutide monotherapy (3 mg, 7 mg, and 14 mg) was associated with dose-dependent reductions in HbA1c and body weight over 26 weeks compared to placebo in patients with type 2 diabetes. The safety profile was consistent with the GLP-1 receptor agonist class, with gastrointestinal events being the most commonly reported adverse events.”

Cycle: 26 weeks

“The OASIS 1 trial (n=667) reported that oral semaglutide 50 mg once daily was associated with a mean body weight reduction of 15.1% vs 2.4% with placebo over 68 weeks in adults with overweight or obesity without type 2 diabetes. Gastrointestinal adverse events (mostly mild to moderate) were reported in 80% of the oral semaglutide group.”

Cycle: 68 weeks

“In Huberman Lab Episode 197, Dr. Craig Koniver and Dr. Huberman discussed GLP-1 analogs including oral formulations, noting the importance of sourcing from reputable FDA-regulated compounding pharmacies and the differences in bioavailability between oral and injectable routes of administration.”

“6 months on Rybelsus 14mg. Lost 20 lbs total which I'm happy with even though it's slower than injectable. The first 2 months were rough with nausea but it settled down. Having to plan my mornings around the fasting window is inconvenient but manageable. My A1C also dropped from 6.1 to 5.4.”

Cycle: 24 weeks

“Started on 3mg and titrated to 7mg over 8 weeks. Lost about 11 lbs in 3 months at the 7mg dose. Side effects have been very manageable compared to what people describe on injectables. The morning fasting routine took some getting used to but it's second nature now. No needle anxiety is worth the trade-off in slower results.”

Cycle: 12 weeks

“Rybelsus has been underwhelming compared to what I expected from all the Ozempic hype. Only about 10 lbs in 5 months. My doctor said the oral bioavailability is much lower than injectable. The acid reflux was unexpected and persistent. Considering switching to injectable if insurance will cover it.”

Cycle: 20 weeks

“Taking Rybelsus 14mg daily for weight loss. Down about 15 lbs in 4 months, which is slower than what people report on injectable sema. The fasting requirement is annoying — have to take it 30 min before eating or drinking anything, even water. But no needles is a huge plus for me.”

Cycle: 16 weeks

“The FDA issued a safety communication in July 2024 reporting multiple adverse events associated with compounded injectable semaglutide products, including cases requiring hospitalization. Dosing errors were identified as a primary concern, with reports of patients self-administering 5 to 20 times the intended dose. The FDA noted it had received 392 adverse event reports related to compounded semaglutide as of November 2024.”

“In AMA #64, Dr. Attia discussed how compounding pharmacies have affected the availability of GLP-1 drugs, noting that compounded formulations may offer customized dosages or alternative administration routes not available in FDA-approved versions, while also addressing quality control considerations for compounded drug formulations.”

“6 months on compounded sema, down 30 lbs. Price was the deciding factor — $150/month through a telehealth provider. Worried about the FDA crackdown on compounders now that the shortage is ending. If they shut it down I honestly don't know what I'll do, can't afford $1,000+/month.”

Cycle: 24 weeks

“Switched compounding pharmacies twice because the first batch felt way stronger than what I was used to on brand Ozempic. The second pharmacy felt weaker. Lost about 12 lbs in 12 weeks but the inconsistency made me nervous. Going back to brand when I can afford it.”

Cycle: 12 weeks

“Got compounded sema from a 503B pharmacy for about $200/month vs $1,300 for brand-name Wegovy. Results have been comparable to what people report on the brand version — 24 lbs down in 20 weeks. My main concern is whether the potency is consistent batch to batch.”

Cycle: 20 weeks

“This Phase 2 trial (n=338) reported that retatrutide, a GLP-1/GIP/glucagon triple-receptor agonist, was associated with dose-dependent body weight reductions of up to 24.2% at the 12 mg dose over 48 weeks. At 48 weeks, 100% of participants receiving 12 mg achieved at least 5% weight reduction, and 83% achieved at least 15%.”

Cycle: 48 weeks

“On the goop podcast, Huberman described retatrutide as a milder agonist of GLP-1 that also increases glucagon and GIP, noting it hits three different pathways each more subtly. He characterized it as a next-generation compound in the GLP-1 class, noting the Phase 2 data showed substantial body weight reductions of up to 24% at 48 weeks.”

“Only 8 weeks in at a lower dose. Lost about 12 lbs so far. Side effects are more tolerable than when I was on semaglutide, oddly enough. The triple-agonist mechanism is interesting but I'm cautious about using something still in trials. Hard to find reliable sourcing info.”

Cycle: 8 weeks

“Weight loss has been dramatic — 25 lbs in 16 weeks — but the nausea is worse than anything I experienced on tirzepatide. Had to slow the titration way down. Sourcing is the biggest concern — no way to verify purity without third-party testing. Waiting for the FDA-approved version.”

Cycle: 16 weeks

“Sourced research-grade retatrutide after reading the Phase 2 data. Down 30 lbs in 12 weeks which is beyond anything I experienced on semaglutide. GI sides were rough the first month but appetite suppression is on another level. Fully aware this is not FDA-approved — monitoring bloods closely.”

Cycle: 12 weeks

“The LEADER trial (n=9,340) reported that liraglutide 1.8 mg daily was associated with a lower rate of the composite cardiovascular outcome (death from cardiovascular causes, nonfatal MI, or nonfatal stroke) compared to placebo over a median follow-up of 3.8 years in patients with type 2 diabetes and high cardiovascular risk.”

Cycle: 197 weeks

“The SCALE trial (n=3,731) reported a mean weight loss of 8.4 kg with liraglutide 3.0 mg vs 2.8 kg with placebo over 56 weeks. Gastrointestinal events were the most commonly reported adverse events, with nausea observed in 40.2% of the liraglutide group vs 14.7% in the placebo group.”

Cycle: 56 weeks

“In AMA #29, Dr. Attia noted he first prescribed liraglutide in 2014, describing it as less impactful for most patients compared to semaglutide. He observed that appetite suppression and weight reduction were more modest with liraglutide, and the daily injection burden was a practical drawback compared to weekly alternatives.”

“Stayed at 1.8mg because the side effects were manageable there. Lost 22 lbs over 5 months. Not as fast as people on Ozempic, but I appreciated the more gradual loss. Less muscle wasting than what I've read about higher-dose GLP-1s.”

Cycle: 20 weeks

“Switched from Saxenda to Wegovy after 4 months. Daily injections were a hassle and the weight loss was underwhelming — only about 10 lbs. Nausea never fully went away. The convenience of weekly dosing with semaglutide was a game changer.”

Cycle: 16 weeks

“Lost about 18 lbs over 6 months. Not as dramatic as what people report on semaglutide, but the daily injection routine got old fast. Nausea was worst during the first 3 weeks of titration.”

Cycle: 24 weeks

“Dr. Rhonda Patrick discussed acetyl-L-carnitine on FoundMyFitness, noting its role in mitochondrial function and fatty acid oxidation. She described L-carnitine as a key nutrient for mitochondrial fatty acid transport and noted research on its potential to support metabolic function during aging.”

“A meta-analysis of 9 RCTs (911 participants) reported that participants receiving L-carnitine experienced a weight reduction of -1.33 kg (95% CI: -2.09 to -0.57) compared to control groups.”

“A meta-analysis of 37 randomized controlled trials (2,292 participants) reported that L-carnitine supplementation was associated with a body weight reduction of -1.21 kg and reduced fat mass. Dose-response analysis indicated that approximately 2,000 mg/day was associated with the greatest observed reduction. No significant changes in waist circumference or body fat percentage were noted.”

“Took 3g/day split into two doses. Lost about 5 lbs over 12 weeks while recomping. The body odor side effect at this dose is no joke — had to back down to 2g eventually. Felt like recovery between sessions improved.”

Cycle: 12 weeks

“Ran L-carnitine for 8 weeks alongside a caloric deficit and 5x/week training. Lost 3 lbs which is hard to attribute to the supplement vs the deficit. Didn't notice a dramatic difference but energy during fasted cardio felt slightly better.”

Cycle: 8 weeks

“Lost about 4 lbs over 12 weeks while keeping diet and training the same. Not dramatic but I noticed better endurance during cardio sessions. The fishy smell is real — had to take it with meals to manage it.”

Cycle: 12 weeks

“Peter Attia discussed GLP-1 agonists on The Drive podcast, noting that tirzepatide targets both the GLP-1 and GIP receptors. He described lean mass loss as a key concern, observing that approximately 39-40% of total weight lost in clinical trial data was lean mass, and emphasized the importance of resistance training and protein intake for users of these compounds.”

“In the SURMOUNT-4 trial, participants who continued tirzepatide after a 36-week run-in period (mean weight reduction of 20.9%) reported an additional -5.5% weight change versus +14.0% with placebo switch over the subsequent 52 weeks. At week 88, 89.5% of continued-treatment participants maintained at least 80% of initial weight reduction.”

Cycle: 88 weeks

“In a 72-week phase 3 trial of 2,539 adults, participants receiving tirzepatide reported mean weight reductions of -16.0% (5mg), -21.4% (10mg), and -22.5% (15mg) compared to -2.4% with placebo. The most common adverse events were gastrointestinal.”

Cycle: 72 weeks

“Lost 15 lbs at 12 weeks on 5mg dose. Results were decent but I'm concerned about what happens when I stop — everything I've read says the weight comes back. The fatigue in weeks 2-6 was hard to deal with while working full time.”

Cycle: 12 weeks

“Down 22 lbs at 12 weeks on 10mg. The sulfur burps are real and embarrassing but manageable. Appetite dropped significantly — I have to set reminders to eat. Prioritizing protein and resistance training to maintain muscle.”

Cycle: 12 weeks

“Switched from semaglutide to tirzepatide at month 4 and the difference was noticeable. Lost 35 lbs in 16 weeks on tirz. Nausea was there but less intense than what I experienced on sema. Energy levels stayed consistent.”

Cycle: 16 weeks

“Dr. Zachary Knight discussed GLP-1 agonists on the Huberman Lab podcast, noting that by amplifying GLP-1 signaling and having long half-lives for continuous appetite suppression, drugs like semaglutide have been observed to be associated with approximately 16% weight reduction over a year in clinical data.”

“Over 104 weeks, the semaglutide group reported a mean body weight change of -15.2% versus -2.6% with placebo. The most common adverse events were gastrointestinal in nature.”

Cycle: 104 weeks

“In a 68-week trial of 1,961 adults with overweight or obesity without diabetes, participants receiving semaglutide 2.4mg once weekly reported a mean body weight change of -14.9% compared to -2.4% with placebo.”

Cycle: 68 weeks

“Only lost 8 lbs in 12 weeks and the GI side effects were brutal. Couldn't keep food down for the first 3 weeks of each dose increase. Discontinued after 12 weeks — not worth it for me.”

Cycle: 12 weeks

“Down 42 lbs at 6 months. This completely changed my relationship with food — the food noise just stopped. I still lift and prioritize protein. Side effects were minimal after the first two weeks of each dose increase.”

Cycle: 24 weeks

“Results were slower than expected — about 14 lbs in 12 weeks. Couldn't tolerate the 2.4mg dose so stayed at 1.7mg. The nausea was debilitating for the first month. Lost some muscle mass despite lifting 4x/week.”

Cycle: 12 weeks

“Lost 28 lbs over 16 weeks. Nausea was rough during titration but leveled off around week 6. Appetite suppression was dramatic — had to force myself to hit protein targets.”

Cycle: 16 weeks