In people with poorly controlled type 2 diabetes treated with basal insulin in this randomized clinical trial with 1,428 participants, weekly tirzepatide compared to prandial insulin as add-on treatment with insulin glargine demonstrated reductions in HbA1c and body weight with less hypoglycemia.
Key points What is the effect on glycemic control of adding once-weekly tirzepatide versus thrice-daily prandial insulin lispro to insulin glargine therapy in type 2 diabetes treated with inadequately controlled basal insulin? Findings In this randomized clinical trial (N = 1428), the mean change in hemoglobin A 1c (HbA 1c) at week 52 was −2.1% with tirzepatide versus −1.1% with insulin lispro; Treatment differences were statistically significant with less hypoglycemia and more body weight reduction with tirzepatide. Meaning The addition of once-weekly tirzepatide versus prandial insulin lispro to insulin glargine in basal insulin-treated patients with type 2 diabetes and inadequate glycemic control resulted in greater reductions in HbA 1c along with greater weight loss and less hypoglycemia. |
Importance
Tirzepatide is a glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist used for the treatment of type 2 diabetes. The efficacy and safety of adding tirzepatide versus prandial insulin to treatment has not been described. in patients with inadequate glycemic control with basal insulin.
Aim
To evaluate the efficacy and safety of tirzepatide versus insulin lispro as add-on therapy to insulin glargine.
Design, environment and participants
This open-label Phase 3b clinical trial was conducted at 135 sites in 15 countries (participants enrolled from October 19, 2020 to November 1, 2022) in 1,428 adults with type 2 diabetes taking basal insulin.
Interventions
Participants were randomly assigned (in a 1:1:1:3 ratio) to receive once-weekly subcutaneous injections of tirzepatide (5 mg [n = 243], 10 mg [n = 238], or 15 mg [ n = 236]) or prandial insulin lispro three times a day (n = 708).
Main results and measures
Results included noninferiority of tirzepatide (pooled cohort) versus insulin lispro, both plus insulin glargine, on change in HbA 1c from baseline at week 52 (margin of noninferiority, 0.3%). Key secondary endpoints included change in body weight and the percentage of participants achieving the hemoglobin A 1c (HbA 1c) goal of less than 7.0%.
Results
Among 1,428 randomized participants (824 [57.7%] women; mean [SD] age, 58.8 [9.7] years; mean [SD] HbA 1c, 8.8% [1.0%]), 1,304 (91.3%) completed the trial. At week 52, the estimated mean change from baseline in HbA 1c with tirzepatide (pooled cohort) was −2.1% versus −1.1% with insulin lispro, resulting in mean HbA levels 1c of 6.7% vs. 7.7% (estimated treatment difference, −0.98% [95% CI, −1.17% to −0.79%]; P < 0.001); The results met the non-inferiority criteria and statistical superiority was achieved.
The 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 achieving 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%).
Rates of hypoglycemia events (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.
Conclusions and relevance In people with poorly controlled type 2 diabetes treated with basal insulin, weekly tirzepatide compared to prandial insulin as add-on treatment with insulin glargine demonstrated reductions in HbA 1c and body weight with less hypoglycemia. |
