Findings showed that addition of subcutaneous tirzepatide, vs placebo, to titrated insulin glargine led to statistically significant improvements in glycemic control after 40 weeks among patients with type 2 diabetes and inadequate glycemic control despite treatment with insulin glargine.

• This randomized clinical trial included 475 adults with type 2 diabetes and inadequate glycemic control while treated with once-daily insulin glargine with or without metformin.

• Patients were randomly assigned to receive once-weekly subcutaneous injections of 5-mg (n = 116), 10-mg (n = 119), or 15-mg (n = 120) tirzepatide or volume-matched placebo (n = 120) over 40 weeks; tirzepatide was started at 2.5 mg/week and escalated by 2.5 mg every 4 weeks until the assigned dose was achieved.

• Tirzepatide doses of 10-mg and 15-mg resulted in mean glycated hemoglobin A _1c (HbA _1c ) change from baseline to week 40 of −2.40% and −2.34%, respectively, vs −0.86% with placebo (10 mg: difference vs placebo, −1.53%; 15 mg: difference vs placebo, −1.47%).

• Compared to baseline, mean HbA _1c change was −2.11% with 5-mg tirzepatide (difference vs placebo, −1.24%).

• Relative to baseline, mean body weight change with 5-mg tirzepatide, 10-mg tirzepatide, and with 15-mg tirzepatide was −5.4 kg, −7.5 kg, and −8.8 kg, respectively, vs 1.6 kg with placebo (5 mg: difference, −7.1 kg; 10 mg: difference, −9.1 kg; 15 mg: difference, −10.5 kg).

• HbA _1c less than 7% was present in higher percentages of patients treated with tirzepatide vs those treated with placebo (85%-90% vs 34%).

• Diarrhea (12%-21% vs 10%) and nausea (13%-18% vs 3%) were the most common treatment-emergent adverse events in the tirzepatide groups vs placebo group.