Common (>10% users in published RCTs / community reports):

• Increased appetite (>50% of users, often pronounced) — this is the #1 dose-limiting effect for weight-conscious users
• Water retention / edema (~30-50% of users) — peripheral, sometimes facial, weeks 2-8 most pronounced; typical 2-5 lb water gain, sometimes 5-10 lb
• Daytime fatigue / drowsiness / "weighted down" feeling (~30-50% of users) — second major dose-limiting effect; sometimes severe enough to require discontinuation
• Mild headache (especially weeks 1-2)
• Vivid dreams / sleep changes
• Mild numbness / tingling in extremities (paresthesia — fluid retention near nerve compression points)
• Joint or muscle aches (fluid retention in joint capsules)
• Mild fasting glucose elevation (5-20 mg/dL; bigger in pre-diabetic users)

Less common (1-10%):

• Carpal tunnel-like symptoms (median nerve compression from soft-tissue swelling; resolves on dose reduction)
• Mild blood pressure elevation (fluid expansion + mild aldosterone effect)
• Mild HbA1c elevation at chronic dosing (0.1-0.3 over 6+ months)
• Resting heart rate increase (mild; sometimes 5-10 bpm)
• Lipid panel shifts (variable; sometimes triglycerides ↑)
• Mild increase in cortisol (modest; smaller than GHRP-6 but bigger than ipamorelin)
• Mild increase in prolactin (modest; usually subclinical but worth tracking)
• Mild aldosterone elevation (driving the sodium/water retention — predictable, not pathologic at typical doses)

Rare-serious (<1% but worth knowing):

• Congestive heart failure exacerbation in frail elderly — documented signal in the Adunsky 2011 Phase 3 hip-fracture trial. Mechanism: fluid retention + mild aldosterone + IGF-1-mediated cardiac remodeling on top of pre-existing cardiac dysfunction. Likely much smaller absolute risk in healthy younger adults but the signal exists in the regulatory record.
• Insulin resistance progression / new-onset diabetes in genetically susceptible users on chronic high-dose protocols. Plausible mechanism (chronic supraphysiologic GH antagonizes insulin); not commonly observed at therapeutic doses with bloodwork-guided dosing, but the long-term n is small.
• Theoretical IGF-1-mediated cancer concern — chronic supraphysiologic IGF-1 elevation has been associated in epidemiologic studies with increased risk of several cancers (prostate, breast, colorectal). Not demonstrated in MK-677 trials specifically but Nass 2008 was 2 years; longer follow-up doesn't exist. The concern is theoretical at therapeutic doses but real-but-unquantified at chronic high-dose multi-year use.
• Increase in symptoms of congestive heart failure observed in the Nass 2008 healthy-elderly trial (small absolute number but concerning given a healthy-elderly population).
• Severe hypoglycemia — rare; described in users combining MK-677 with insulin or aggressive glucose-lowering.
• Rare: pituitary stalk effects, severe edema, hyperglycemia requiring discontinuation.
• Acromegaly-spectrum effects (jaw/nose/hand growth, organomegaly) — not clinically observed at therapeutic doses, but the ceiling concern of any chronic GH-axis intervention. The Nass 2008 2-year trial did not show acromegaly signs, but extrapolation to multi-year off-label use at higher doses is uncharacterized.

Specific watch periods:

• Weeks 1-4 — peak appetite, edema, drowsiness, headache. Most users discontinue here if they're going to discontinue. Titrate down or stop if drowsiness/edema is debilitating.
• Weeks 6-12 — peak IGF-1 elevation; check labs (IGF-1, fasting glucose, HbA1c, IGFBP-3). Reduce dose if IGF-1 >300 ng/mL or fasting glucose climbing.
• Months 3-6 — cumulative metabolic shifts (HbA1c, lipid panel) become detectable; re-evaluate.
• Months 6-24 — long-term use territory; evidence base ends at 2 years (Nass 2008). Beyond that is uncharted.