SURPASS-III

Efficacy and safety of tirzepatide versus titrated insulin degludec in people with type 2 diabetes

Study design: Open-label, parallel-group, multicentre, multinational, phase 3 study

Population

Number of patients studied: 1437
Inclusion criteria: Aged ≥18 years, baseline HbA1c 7·0-10·5%, BMI ≥ 25 kg/m2, stable weight, insulin-naive, metformin treatment alone or with SGLT2 inhibitor for ≥ 3 months
Exclusion criteria: Not specified

Interventions

Experimental group: Once-weekly subcutaneous injection of tirzepatide (5, 10, or 15 mg)
Control group: Once-daily subcutaneous injection of titrated insulin degludec

Primary outcome: Non-inferiority of tirzepatide 10 mg or 15 mg, or both, versus insulin degludec in mean change from baseline in HbA1c at week 52

Secondary outcomes

Non-inferiority of tirzepatide 5 mg versus insulin degludec in mean change from baseline in HbA1c at week 52; superiority of all doses of tirzepatide versus insulin degludec in mean change from baseline in HbA1c and bodyweight; proportion of participants achieving HbA1c of less than 7·0% (<53 mmol/mol) at week 52

Safety outcomes or Adverse Events

Most common adverse events in tirzepatide-treated participants were gastrointestinal events; higher incidence of nausea (12-24%), diarrhea (15-17%), decreased appetite (6-12%), and vomiting (6-10%) in participants treated with tirzepatide than insulin degludec (2%, 4%, 1%, and 1%, respectively); hypoglycemia (<54 mg/dL or severe) reported in 1-2% of tirzepatide participants versus 7% in insulin degludec group; treatment discontinuation due to adverse events more common in tirzepatide groups

Conclusion

In patients with type 2 diabetes, tirzepatide (5, 10, and 15 mg) was superior to titrated insulin degludec, with greater reductions in HbA1c