SURPASS-2: trial summary, limitations and UK relevance

Key findings

SURPASS-2 was the first head-to-head trial directly comparing a dual GIP/GLP-1 receptor co-agonist against a GLP-1 receptor agonist in adults with type 2 diabetes. Tirzepatide, across its 5, 10 and 15 mg weekly doses, produced greater reductions in HbA1c and body weight than semaglutide 1.0 mg at 40 weeks. The comparator dose reflects semaglutide's approved glycaemic-control regimen for type 2 diabetes, not the higher 2.4 mg dose licensed specifically for weight management. SURPASS-2 provided the first direct evidence that dual incretin agonism can outperform GLP-1 mono-agonism on both glycaemic and weight endpoints within the same trial.

Safety summary

GI adverse events (nausea, diarrhoea, vomiting) occurred at a broadly similar or somewhat higher frequency with tirzepatide relative to semaglutide 1.0 mg, concentrated during dose titration. Hypoglycaemia rates were low in both arms given the absence of concomitant sulfonylurea/insulin use in most participants.

Limitations

• Semaglutide 1.0 mg is the licensed glycaemic-control dose for type 2 diabetes, not the 2.4 mg weight-management dose (Wegovy) — the comparison does not generalise to a weight-management head-to-head.
• 40-week duration cannot establish long-term durability, cardiovascular outcomes, or safety beyond the trial period.
• Active-comparator design provides relative rather than placebo-controlled efficacy data.
• Trial population was limited to those inadequately controlled on metformin monotherapy; generalisability to other treatment-experience profiles is limited.

UK relevance

Directly informs UK clinical choice between tirzepatide (Mounjaro) and semaglutide at the glycaemic-control dose for adults with type 2 diabetes, relevant to NHS prescribing pathways and NICE technology-appraisal comparisons.