SURPASS-1

Study record

Population

Adults with type 2 diabetes, HbA1c 7.0–9.5% despite diet and exercise, BMI ≥23, and stable weight within 5% for three months. No oral antihyperglycemic medication in the prior three months; injectable-diabetes-therapy-naive with specified short-term insulin exceptions. Selected exclusions included prior pancreatitis and eGFR <30. These are trial eligibility criteria, not a treatment recommendation.

Read source · Supplementary materialInclusion/exclusion criteria, printed pages 1–3

Formulation

Tirzepatide injection and injectable placebo. The corrected appendix figure establishes the injectable interventions; exact preparation and concentration are not specified in the verified appendix sections.

Inspect extraction gap · Supplementary materialFigure S1, printed page 16; formulation detail incomplete

Route

Subcutaneous weekly injection; the appendix describes thigh or abdomen administration, or upper arm administration by a caregiver.

Read source · Supplementary materialFigure S1 and accompanying note, printed page 16

Dose & frequency

Assigned maintenance doses were 5, 10 or 15 mg once weekly. Figure S1 starts at 2.5 mg and increases by 2.5 mg every four weeks, reaching assigned doses at weeks 4, 12 or 20. Placebo was injected weekly. This is the trial schedule, not a personal dosing or cycling plan.

Read source · Supplementary materialFigure S1, printed page 16; visually verified

Study design

Randomized 1:1:1:1 trial with 478 participants. The efficacy estimand excludes post-discontinuation/rescue data and uses MMRM. The treatment-regimen estimand incorporates those events and imputes missing outcomes using placebo-arm data. These analyses answer different questions.

Read source · Supplementary materialFigure S1, page 16; Additional Statistical Analysis Methods, pages 4–6

Duration

40 weeks of treatment followed by four weeks of safety follow-up. Screening and lead-in precede randomization; this was not a repeated on/off cycle.

Read source · Supplementary materialFigure S1, printed page 16; visually verified

Reported findings

At week 40, treatment-regimen estimates for 5/10/15 mg versus placebo were HbA1c changes of −1.75/−1.71/−1.69 versus −0.09 percentage points, and weight changes of −6.3/−7.0/−7.8 versus −1.0 kg. Analysis N=121/121/120/113. These adjusted, imputed estimates differ from the primary efficacy-estimand results; numeric dose ordering does not establish superiority between doses.

Read source · Supplementary materialTable S6, printed pages 14–15; treatment-regimen estimand and footnotes; selected cells visually verified

Adverse events

Table S3 reports mostly mild or moderate gastrointestinal events, but includes one severe nausea and one severe vomiting report in the 5 mg arm. Those reports may concern the same participant and must not be summed as unique patients. The table is not a complete all-event safety summary.

Inspect extraction gap · Supplementary materialTable S3, printed page 10; selected gastrointestinal severity counts visually verified

Monitoring

The protocol required glucose monitoring and study diaries. Suspected pancreatitis and severe or serious unexplained abdominal pain underwent adjudication; isolated enzyme elevations required additional diagnostic investigation and/or suggestive symptoms for adjudication. Rescue treatment was specified for persistent severe hyperglycemia. These procedures are not a personal monitoring plan.

Read source · Supplementary materialInclusion criteria, pages 1–2; rescue medication and Adjudicated Events, pages 3–4