SURPASS-4

Study record

Population

Adults with type 2 diabetes, HbA1c 7.5–10.5%, BMI ≥25 and elevated cardiovascular risk, taking metformin, sulfonylurea and/or an SGLT2 inhibitor. 2,002 randomized; 1,995 treated.

Read source · Full-text reportParticipants; Results, pp1813–1815

Formulation

Tirzepatide in a prefilled syringe; comparator insulin glargine (Basaglar), U100 in a 3 mL prefilled pen.

Read source · Full-text reportProcedures, p1813

Route

Weekly subcutaneous tirzepatide versus daily subcutaneous insulin glargine.

Read source · Full-text reportProcedures, p1813

Dose & frequency

Tirzepatide began at 2.5 mg weekly and increased by 2.5 mg every four weeks to assigned 5, 10 or 15 mg. One intolerance-related reduction to 5 or 10 mg was allowed during escalation. Glargine began at 10 U/day and was titrated to fasting glucose below 100 mg/dL. This is the reported study regimen.

Read source · Full-text reportProcedures, p1813

Study design

Open-label randomized active-controlled phase 3 trial, allocation 1:1:1:3. Background oral medicines continued; cardiovascular events and possible pancreatitis underwent blinded independent adjudication.

Read source · Full-text reportRandomisation and masking; Outcomes, pp1813–1814

Duration

Primary efficacy at 52 weeks; variable treatment extension up to another 52 weeks, followed by four weeks of safety follow-up. Not all participants received 104 weeks of treatment.

Read source · Full-text reportProcedures, p1813

Reported findings

At 52 weeks, efficacy-estimand HbA1c changes were −2.24, −2.43 and −2.58 percentage points versus −1.44 with glargine; weight changes −7.1, −9.5 and −11.7 kg versus +1.9 kg. Over full follow-up, MACE-4 affected 47/995 versus 62/1,000 (HR 0.74; 95% CI 0.51–1.08), which did not establish cardiovascular superiority.

Read source · Full-text reportTables2 and4, pp1818/1820; estimand definitions p1814

Adverse events

Across full follow-up, serious adverse events affected 48/329, 54/328 and 41/338 versus 193/1,000. Adverse events led to treatment discontinuation in 37/329, 28/328 and 36/338 versus 54/1,000. Deaths numbered 15, 2 and 8 versus 35 and are included in serious-event and discontinuation counts.

Read source · Full-text reportTable3 and footnote, p1819

Monitoring

Glargine titration used the median of the last three fasting self-monitored glucose values. Safety included adverse events, hypoglycemia, vital signs, laboratory measures and adjudicated cardiovascular/pancreatic events. Background medicines could be reduced for hypoglycemia.

Read source · Full-text reportProcedures and Outcomes, pp1813–1814