# Ghrelin-receptor agonists (MK-677, anamorelin, relamorelin) for weight gain

Summary: MK-677 (ibutamoren) reliably increases body weight and "fat-free mass" in human RCTs, but a substantial fraction of the gain is body water, with additional fat deposition, no strength/function gain, and worrying glucose and cardiovascular signals in elderly trials. It is not approved anywhere and is sold grey-market as a "research chemical." Anamorelin has properly conducted phase 3 trials (ROMANA 1/2) and is approved in Japan for cancer cachexia; it produces modest lean-body-mass gain but no handgrip improvement, and was rejected by the EMA and never approved by the FDA. Relamorelin is same-class but developed for gastroparesis rather than body composition.

**Claim:** In the Nass et al. 2008 two-year RCT, MK-677 25 mg/day in healthy older adults (n=65, ages 60-81) increased fat-free mass by 1.1 kg (95% CI 0.7 to 1.5) vs a 0.5 kg loss on placebo (p<0.001), but the increase was mostly total body water and did NOT improve muscle strength or function; body weight rose 2.7 kg on MK-677 vs 0.8 kg on placebo.
- **Confidence:** C1
- **Sources:** https://pubmed.ncbi.nlm.nih.gov/18981485/ ; https://pmc.ncbi.nlm.nih.gov/articles/PMC2757071/
- **Date checked:** 2026-04-14
- **Cross-verified:** yes
- **Notes:** Limb fat also increased more on MK-677 (+1.1 kg) than placebo (+0.24 kg) - so a large share of "weight gain" is water and fat, not functional muscle. This is the single most important caveat to forum claims.

**Claim:** In Svensson et al. 1998 (often miscited as "Murphy 2001"), 2 months of MK-677 25 mg/day in 24 obese men increased fat-free mass and transiently increased basal metabolic rate; a separate Murphy 2001 18-month trial in ~292 postmenopausal osteoporotic women studied MK-677 combined with alendronate for bone markers, not weight gain as primary outcome.
- **Confidence:** C2
- **Sources:** https://pubmed.ncbi.nlm.nih.gov/9467542/ ; https://www.researchgate.net/figure/Body-composition-during-2-month-treatment-with-MK-677-25-mg-or-placebo-daily-in-obese_fig1_13762427
- **Date checked:** 2026-04-14
- **Cross-verified:** yes
- **Notes:** The brief's "Murphy 2001 obese women" label appears to conflate two separate studies. Svensson 1998 is the obese-subject body-composition trial; Murphy 2001 is the postmenopausal osteoporosis/alendronate trial. Either way, weight gain signal in short-term trials is real but includes water and fat.

**Claim:** MK-677 consistently worsens glucose metabolism: fasting glucose rose ~0.3 mmol/L (~5 mg/dL) on average, HbA1c rose ~0.2% vs -0.1% on placebo over 12 months, insulin sensitivity (Quicki index) decreased, and case reports describe new-onset diabetes in recreational bodybuilding users.
- **Confidence:** C1
- **Sources:** https://pmc.ncbi.nlm.nih.gov/articles/PMC2757071/ ; https://www.endocrine-abstracts.org/ea/0086/ea0086p341 ; https://pmc.ncbi.nlm.nih.gov/articles/PMC9331610/
- **Date checked:** 2026-04-14
- **Cross-verified:** yes
- **Notes:** Glucose deterioration is mechanistically expected from elevated GH/IGF-1 and is the main signal that limits chronic use in older / prediabetic populations.

**Claim:** In an earlier MK-677 trial in elderly hip-fracture patients (Adunsky et al.), congestive heart failure occurred in 6.5% on ibutamoren vs 1.7% on placebo, concentrated in participants over 80 with prior CHF history; this CHF signal plus fluid retention is the main cardiovascular safety concern and is plausibly related to GH-driven sodium/water retention.
- **Confidence:** C1
- **Sources:** https://pubmed.ncbi.nlm.nih.gov/21067829/ ; https://pmc.ncbi.nlm.nih.gov/articles/PMC2757071/
- **Date checked:** 2026-04-14
- **Cross-verified:** yes
- **Notes:** Independent verifier confirmed the 6.5% vs 1.7% CHF figures against the primary Adunsky source (PMID 21067829). MK-677 has never been FDA-approved and development was halted in part for this safety profile. Ubiquitous grey-market "research chemical" sale in bodybuilding channels (forum use = C4) far outstrips the evidence base.

**Claim:** Anamorelin in ROMANA 1 and ROMANA 2 (phase 3, NSCLC cachexia, 12 weeks, 100 mg/day oral) increased lean body mass by +0.99 kg (95% CI 0.61-1.36) vs -0.47 kg on placebo in ROMANA 1 and +0.65 kg (0.38-0.91) vs -0.98 kg in ROMANA 2 (both p<0.0001), but did NOT improve handgrip strength in either trial.
- **Confidence:** C1
- **Sources:** https://pubmed.ncbi.nlm.nih.gov/26906526/ ; https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00558-6/abstract
- **Date checked:** 2026-04-14
- **Cross-verified:** yes
- **Notes:** The handgrip-strength miss is exactly why the EMA rejected Adlumiz in 2017 - "marginal effect on lean body mass and no proven effect on hand grip strength or patients' quality of life."

**Claim:** Anamorelin is approved in Japan (11 December 2020, marketed January 2021) for cancer cachexia in NSCLC, gastric, pancreatic, and colorectal cancer; it was rejected by the EMA in 2017 and has not been approved by the FDA for any indication. Japanese ONO-7643-04 trial showed +1.38 kg vs -0.17 kg LBM at 12 weeks in NSCLC.
- **Confidence:** C1
- **Sources:** https://pmc.ncbi.nlm.nih.gov/articles/PMC7890143/ ; https://onlinelibrary.wiley.com/doi/full/10.1002/jcsm.12675 ; https://ar.iiarjournals.org/content/45/3/865
- **Date checked:** 2026-04-14
- **Cross-verified:** yes
- **Notes:** Approval is narrowly for cachexia in specific cancers, not for healthy-person bulking. Effect size is modest (~1 kg LBM over 12 weeks) and the drug does not translate lean-mass gain into measurable strength improvement, which is the main clinical critique.

**Claim:** Relamorelin (RM-131) is a pentapeptide GHSR agonist developed primarily for diabetic gastroparesis and chronic constipation, not body composition; phase 2b trials show accelerated gastric emptying and symptom improvement but dose-related worsening of glycemic control in ~14.5% of diabetic recipients. It is not approved and has no body-composition RCT data.
- **Confidence:** C2
- **Sources:** https://en.wikipedia.org/wiki/Relamorelin ; https://pubmed.ncbi.nlm.nih.gov/28760384/ ; https://pmc.ncbi.nlm.nih.gov/articles/PMC10696281/
- **Date checked:** 2026-04-14
- **Cross-verified:** yes
- **Notes:** Mentioned for class-completeness. Any "weight gain" use would be extrapolation from mechanism, not evidence. Tag C4 for body-composition claims outside gastroparesis.