SURPASS trial programme (revision 8)
Old revision·17:08, 4 Oct 2024·TrialsTabitha
| SURPASS trial programme | |
|---|---|
| Drug | Tirzepatide 5, 10 and 15 mg weekly |
| Indication | Type 2 diabetes |
| Notable member | SURPASS-2, head-to-head with semaglutide |
| Topic infobox · conventions | |
The SURPASS trial programme is the phase 3 series that established tirzepatide for type 2 diabetes. Its trials compared tirzepatide at 5, 10 and 15 mg weekly against placebo, semaglutide 1 mg, insulin degludec, insulin glargine and dulaglutide.[1]
Glycated-haemoglobin reductions across the programme were larger than those reported for any comparator, reaching about 2.0–2.6 percentage points at the higher doses depending on trial and baseline. Weight reduction accompanied them at every dose.[1]
SURPASS-2 is the most cited member because it is a direct head-to-head against semaglutide. The comparator dose was 1 mg — the diabetes dose — not the 2.4 mg used in obesity, a distinction routinely omitted when the trial is summarised.[1]
Constituent trials
[edit]| Trial | Comparator | Notes |
|---|---|---|
| SURPASS-1 | Placebo | Monotherapy in drug-naive participants |
| SURPASS-2 | Semaglutide 1 mg | Open-label head-to-head |
| SURPASS-3 | Insulin degludec | Added to metformin ± SGLT2 inhibitor |
| SURPASS-4 | Insulin glargine | High cardiovascular risk population |
| SURPASS-5 | Placebo | Added to insulin glargine |
| SURPASS-CVOT | Dulaglutide | Cardiovascular outcomes, active comparator |
SURPASS-CVOT is unusual among cardiovascular outcome trials in using an active comparator with an established benefit rather than placebo, which changes what a non-inferiority result means: non-inferiority to an agent that itself reduced events is a stronger statement than non-inferiority to placebo.[1]
Open-label design in SURPASS-2 is a limitation for subjective endpoints and adverse-event reporting, though less so for glycated haemoglobin, which is a laboratory measurement.[2]
References
- ^ a b c d Frías JP, Davies MJ, Rosenstock J, et al. "Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes." New England Journal of Medicine 385(6):503–515 (2021). DOI:10.1056/NEJMoa2107519. PMID 34170647.
- ^ International Council for Harmonisation, E9(R1): Estimands and Sensitivity Analysis in Clinical Trials (2019).