SURPASS-AP-Combo

Study record

Population

Adults with type 2 diabetes, HbA1c 7.5–11.0%, BMI ≥23 and stable weight. Insulin-naive apart from specified gestational or short-term use. Metformin, with or without sulfonylurea, was stable for at least two months. Most randomized participants were enrolled in China.

Read source · Supplementary materialReporting summary page 2 — Population characteristics; primary abstract

Formulation

Protocol-supplied tirzepatide in single-dose prefilled pens; insulin glargine in prefilled pens. This does not describe compounded or research-vial products.

Read source · Study protocolSection 7.1, Table GPHO.3 and section 7.1.1, printed pages 39–40

Route

Weekly subcutaneous tirzepatide versus daily subcutaneous insulin glargine, on the oral medication background.

Read source · Study protocolSection 7.1 and Table GPHO.3, printed page 39

Dose & frequency

Tirzepatide started at 2.5 mg weekly and increased by 2.5 mg every four weeks to the assigned 5, 10 or 15 mg dose. Glargine started at 6 IU/day and was titrated using fasting glucose under the trial algorithm. These are trial procedures, not personal dosing instructions.

Read source · Study protocolSection 7.1, printed page 39

Study design

Open-label, randomized 1:1:1:1 comparison. Randomization was stratified by HbA1c, country and oral medication background. Modified intention-to-treat included randomized participants receiving at least one dose. Primary noninferiority margin was 0.4 percentage points for HbA1c; selected secondary comparisons used multiplicity control.

Read source · Supplementary materialReporting summary pages 2–3 — Randomization, Blinding, Data exclusions and Outcomes

Duration

40-week treatment period followed by four weeks of safety follow-up. This was continuing treatment, not an on/off cycle.

Read source · Study protocolProtocol synopsis — Study design and Safety analysis, printed pages 11–12

Reported findings

Week-40 registry results match the publication abstract: HbA1c changes for tirzepatide 5/10/15 mg versus glargine were −2.24/−2.44/−2.49 versus −0.95 percentage points; weight changes were −5.0/−7.0/−7.2 versus +1.5 kg. Analyses excluded data after rescue or study-drug stopping (last dose plus seven days) and used MMRM. Posted HbA1c denominators were 211/194/193/193; weight denominators were 211/194/193/194. These differ from randomized group sizes. Final-report reconciliation remains incomplete.

Inspect extraction gap · Registry resultsNCT04093752 posted primary HbA1c, secondary 5 mg HbA1c and body-weight outcomes; analysis population descriptions

Adverse events

At least one serious adverse event occurred in 15/230, 14/228 and 15/229 tirzepatide recipients, versus 20/220 glargine recipients. The glargine safety denominator differs from the 230 randomized. Counts concern participants, not episodes or events attributed to treatment. Full nonserious-event and discontinuation reconciliation remains incomplete.

Inspect extraction gap · Supplementary materialSupplementary Table 4, PDF pages 5–6; top-row counts visually verified

Monitoring

Protocol safety analyses included follow-up after discontinuation or rescue. Glucose measurements guided glargine adjustment and hyperglycemia rescue; the protocol required diaries and scheduled glucose profiles. Reporting summary describes central HbA1c and other laboratory testing. Planned procedures do not establish complete observed-event ascertainment.

Read source · Study protocolProtocol synopsis Safety analysis, page 12; section 7.1, page 39; reporting summary page 3