Semaglutide (Ozempic / Wegovy / Rybelsus)

Structure: Acylated GLP-1 analog with 94% homology to native GLP-1. Albumin binding extends half-life to weekly dosing.

Dosage:

• Weight loss (titrate up): 0.25mg/week x4 weeks → 0.5mg/week x4 weeks → 1.0mg/week x4 weeks → 1.7mg/week → 2.4mg/week
• Bodybuilding cut: Most use 0.5-1.0mg/week (lower doses often sufficient for appetite control)
• Oral for type 2 diabetes (Rybelsus): 3mg/day → 7mg/day → 14mg/day
• Oral for weight loss (Wegovy Pill): 1.5mg/day → 4mg/day → 9mg/day → 25mg/day maintenance, at least 1 month per step. The 25mg tablet is the weight-loss equivalent of the 2.4mg weekly injection. Rybelsus and Wegovy Pill tablets are not interchangeable.

Wegovy Pill status:

• Approved in Australia: entered the ARTG on 3 November 2026 for chronic weight management (BMI 30 or more, or 27 or more with a weight-related condition) and cardiovascular risk reduction in adults. No launch date or price at approval, and not PBS-listed for weight loss.
• It is the first oral GLP-1 approved by the TGA for weight management. Lilly's orforglipron (Foundayo), the pill with no food rules, was still awaiting TGA approval at the same time.

Administration:

• SubQ injection once weekly, abdomen/thigh/upper arm, rotate sites
• Oral forms (Rybelsus and Wegovy Pill) must be taken on waking on an empty stomach with no more than 120mL of water, then wait 30 minutes before food, drink or other tablets. Taking it with food or other medicines cuts absorption sharply.
• Oral semaglutide raises levothyroxine exposure, so recheck TSH and free T4 after starting it if you take thyroid hormone (including T4 used on cycle)
• Titrate slowly to minimise GI side effects

Key Notes:

• Extremely effective appetite suppressant — the primary benefit for bodybuilders during cuts
• GI side effects (nausea, vomiting, diarrhoea) are common during titration — start low
• Risk of muscle loss during aggressive caloric deficit — must maintain high protein intake and resistance training
• Improves metabolic markers: HbA1c, fasting glucose, triglycerides, LDL, CRP
• Small risk of pancreatitis — monitor amylase/lipase if abdominal pain occurs
• Can slow gastric emptying significantly — relevant for pre-anaesthesia considerations
• May reduce effectiveness of oral medications (delayed absorption)
• Monitor: fasting glucose, HbA1c, lipid panel, amylase/lipase, liver enzymes

Which markers to run before, during and after, with protocols for athletes on TRT: GLP-1 bloodwork: what to test on semaglutide.

Beyond weight loss, on the 2026 Nature paper showing 12% lifespan extension in aged female mice, what the dose actually scales to and what the study does not tell men on TRT: How semaglutide extended lifespan 12% in old female mice.