Metformin

Structure: Biguanide that reduces hepatic glucose production, increases insulin sensitivity, and delays intestinal glucose absorption. Does not stimulate insulin secretion (no hypoglycaemia risk as monotherapy).

Dosage:

• Insulin sensitiser (with GH/MK-677): 500mg 1-2x/day
• Standard: 500-1000mg 2x/day with meals
• Maximum: 2000-2500mg/day (split doses)

Administration:

• Oral tablet, always take with food (reduces GI side effects)
• Extended-release (XR) formulation significantly reduces GI sides — preferred
• Titrate up: start 500mg/day with dinner for 1-2 weeks, then increase

Key Notes:

• Primary bodybuilding use: counteract insulin resistance caused by GH, MK-677, or insulin use
• GI side effects (bloating, diarrhoea, nausea) are common initially — subside in 2-4 weeks
• Extended-release (XR) formulation is much better tolerated — ask for Metformin XR specifically
• Depletes Vitamin B12 with long-term use — supplement B12 and monitor levels annually
• Does NOT cause hypoglycaemia when used alone (unlike insulin or sulfonylureas)
• Some evidence of anti-aging / longevity benefits (AMPK activation, mTOR modulation)
• Concern: may mildly blunt muscle protein synthesis (mTOR inhibition) — debated
• Take at a different time than post-workout meals if concerned about mTOR blunting
• Monitor: fasting glucose, HbA1c, fasting insulin, Vitamin B12, liver enzymes, kidney function (eGFR)