The addition of once-weekly subcutaneous tirzepatide to insulin glargine had statistically significant improvements in glycemic control compared to placebo for adults with type 2 diabetes (T2D) and inadequate glycemic control, according to a recent study.
Lead investigator Ángel Rodríguez, MD, PhD, Lilly Spain, noted that to his knowledge, the trial was the first to assess the efficacy and adverse event profile of a dual glucose-dependent insulinotropic polypeptide/GLP-1 receptor agonist in combination with basal insulin.
These current results “provide clinically relevant information relative to the use of tirzepatide in combination with a basal insulin that should be of help to clinicians when this treatment option is considered.”
The phase 3, randomized, double-blind, parallel, multicenter, placebo-controlled study was conducted at 45 medical research centers and hospitals, including in the United States, Japan, and Germany for 40 weeks.
Enrollment was performed beginning in August 2019, with the last patient randomized in March 2020 and date of final follow-up in January 2021.
Eligibility included adults with T2D, baseline HbA1c of 7.0% – 10.5% (53 – 91 mmol/mol), and a body mass index (BMI) of ≥23 stable doses of once-daily insulin glargine (>20 IU/d or >0.25 IU/kg/d) with or without metformin (≥1500 mg/d).
They were then randomized in a 1:1:1:1 ratio to receive 5 mg, 10 mg, or 15 mg of tizepatide or volume-matched placebo. All patients started tirzepatide at a 2.5 mg dose and increased by 2.5 mg every 4 weeks until reaching their randomly assigned dose.
The primary efficacy endpoint for the study was the mean change from baseline in HbA1c at week 40, while the primary objective was to compare 10-mg tirzpatide and 150mg tirzepatide dose groups with placebo. Secondary outcomes include mean change in body weight and percentage of patients achieving specified HbA1c levels.
A total of 475 patients were randomized and received ≥1 dose of the study drug, with 451 (94.9%) patients completing the study. At baseline, the patient population had a mean age of 61 years, mean BMI of 33.4, mean HbA1c of 8.31% (67 mmol/mol), while 82.9% (n = 394) were using metformin.
At week 40, the mean HbA1c change from baseline was -2.40% with 10-mg tirzepatide and -2.34% with 15-mg tirzepatide versus -0.86% with placebo.
In fact, tirzepatide doses of 10 mg and 15 mg showed a significantly greater change HbA1c from baseline at 40 weeks compared to placebo
- 10 mg: difference, -1.53%; 97.5% CI, -1.80% to -1.27%, P <.001
- 15 mg: difference, -1.47%; 97.5% CI, -1.75% to -1.20%, P <.001
Data from the treatment regimen estimand show the mean HbA1c change from baseline to week 40 was -2.11% in the 5-mg tirzepatide group (difference versus placebo, -1.24%; 95% CI, -1.48% to -1.01%, P <.001).
Rodriguez and colleagues observed the mean body weight change from baseline compared to placebo (1.6kg) as follows:
- 5.4 kg with 5-mg tirzepatide (difference, -7.1 kg; 95% CI, -8.7 to -5.4)
- 7.5 kg with 10-mg tirzepatide (difference, -9.1 kg; 95% CI, -10.7 to -7.5)
- 8.8kg with 15-mg tirzepatide (difference, =10.5 kg; 95% CI, -12.1 to -8.8; P <.001 for all)
Additionally, a greater percentage of patients treated with 5-mg, 10-mg, and 15-mg tirzepatide versus placebo met the hbA1c target of less than 7.0% at week 40 (85% – 90% versus 34%; P <.001 for all).
Investigators noted the effects of the agent on glycemic control, body weight, lipid levels, and blood pressure were consistent with previously reported studies and “validate its effectiveness” across different patient populations.
The study, “Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes: The SURPASS-5 Randomized Clinical Trial,” was published in JAMA.