Semaglutide

What the studies found

• Substantial weight reduction in obesity

  The STEP programme reported mean weight loss around 15% at 68 weeks versus roughly 2.4% on placebo, in participants without diabetes. Effect sizes were smaller in participants with type 2 diabetes.

• Cardiovascular benefit in an at-risk population

  SELECT enrolled over 17,000 participants with established cardiovascular disease and overweight or obesity, but without diabetes, and reported a roughly 20% reduction in major adverse cardiovascular events over about three years. This is among the strongest outcome data for any weight-management drug.

• Glycaemic control in type 2 diabetes

  The SUSTAIN trials established HbA1c reductions that met or exceeded active comparators, which is the basis of its original licence.

What the evidence does not show

• Weight is regained after stopping. In the STEP 1 extension, participants regained about two-thirds of lost weight within a year of withdrawal, meaning the effect depends on continued use.
• Trials were conducted with supervised dose escalation and dietary support. Outcomes without that structure are not what was measured.
• Long-term safety beyond the trial periods is still accumulating.
• Gastrointestinal adverse effects led a meaningful minority of trial participants to discontinue.

Reported risks and adverse effects

• Common: nausea, vomiting, diarrhoea, constipation. Usually dose-related and often improving over time, but a frequent reason for stopping.
• Pancreatitis has been reported; trials excluded participants with a history of it.
• Gallbladder disease occurs more often than on placebo, likely related to rapid weight loss.
• Rodent studies showed thyroid C-cell tumours. Contraindicated in personal or family history of medullary thyroid carcinoma or MEN 2. Relevance to humans is unestablished but the contraindication stands.
• Reports of non-arteritic anterior ischaemic optic neuropathy are under regulatory review as a possible signal.

This is a summary of what has been reported in the literature, not a complete safety profile. For anything concerning your own health, speak to a doctor.

Regulatory status

Licensed for type 2 diabetes (Ozempic, Rybelsus) and weight management (Wegovy). Prescription-only in the UK, EU and US. Compounded and unlicensed versions have been linked to dosing errors and hospitalisations, and regulators including the MHRA and FDA have issued warnings about them.