Compared with insulin lispro 3 times daily in patients with type 2 diabetes who were also receiving basal insulin, once-weekly tirzepatide reduced hemoglobin A1c(HbA1c) and weight while causing less hypoglycemia. “It is possible that the body weight loss induced by tirzepatide therapy and its reported effect in reducing liver fat content may have led to an improvement in insulin sensitivity and decreased insulin requirements,” the authors write.
The SURPASS-6 randomized clinical trial enrolled 1,428 participants at 135 sites in 15 countries from Oct. 19, 2020, to Nov. 1, 2022. All had poor glycemic control while on basal insulin. They were randomized to open-label once-weekly subcutaneous injections of tirzepatide 5 mg, 10 mg, or 15 mg or prandial insulin lispro 3 times daily while continuing to take basal insulin.
Based on primary outcomes of noninferiority of tirzepatide (pooled cohort) vs insulin lispro of HbA1c change from baseline at week 52, the authors found these results: “Among 1,428 randomized participants (824 [57.7%] women; mean [SD] age, 58.8 [9.7] years; mean [SD] HbA1c, 8.8% [1.0%]), 1,304 (91.3%) completed the trial. At week 52, estimated mean change from baseline in HbA1c with tirzepatide (pooled cohort) was −2.1% vs −1.1% with insulin lispro, resulting in mean HbA1c levels of 6.7% vs 7.7% (estimated treatment difference, −0.98% [95% CI, −1.17% to −0.79%]; P < .001); results met noninferiority criteria and statistical superiority was achieved. Estimated mean change from baseline in body weight was −9.0 kg with tirzepatide and 3.2 kg with insulin lispro (estimated treatment difference, −12.2 kg [95% CI, −13.4 to −10.9]). The percentage of participants reaching HbA1c less than 7.0% was 68% (483 of 716) with tirzepatide and 36% (256 of 708) with insulin lispro (odds ratio, 4.2 [95% CI, 3.2-5.5]). The most common adverse events with tirzepatide were mild to moderate gastrointestinal symptoms (nausea: 14%-26%; diarrhea: 11%-15%; vomiting: 5%-13%). Hypoglycemia event rates (blood glucose level <54 mg/dL or severe hypoglycemia) were 0.4 events per patient-year with tirzepatide (pooled) and 4.4 events per patient-year with insulin lispro.”