SURPASS-5 Data: Tirzepatide Plus Insulin Glargine Improve Glycemic Control in T2D


Data from SURPASS-5 show Eli Lilly's glucagon-like peptide-1 receptor agonist tirzepatide helped improve glycemic control when taken with insulin glargine.

New findings of the SURPASS-5 clinical trial revealed the addition of Eli Lilly’s subcutaneous tirzepatide, compared with placebo, to titrated insulin glargine resulted in statistically significant improvements in glycemic control after 40 weeks among patients with type 2 diabetes (T2D). Results were published in JAMA and build off previous positive findings of the SURPASS program reported in February 2021.

Tirzepatide is a novel investigational once-weekly dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) receptor agonist, which has been found to reduce glycated hemoglobin (A1C) and body weight among adults with T2D.

Although basal insulins are widely used among those with T2D to improve glycemic control, increasing doses can be associated with a heightened risk of hypoglycemia and weight gain, authors explained.

However, “when added to basal insulin, selective GLP-1 receptor agonists have demonstrated improved glycemic control and body weight loss without increasing the risk of hypoglycemia and reducing insulin requirements,” they wrote.

To investigate tirzepatide’s effect as an addition to insulin glargine, researchers recruited 475 adults with T2D and inadequate glycemic control treated with basal insulin alone or basal insulin with metformin.

Throughout the 40-week phase 3 study, which took place at 45 centers around the world, participants received 3 doses of tirzepatide (5 mg [n = 116], 10 mg [n = 119], and 15 mg [n = 120]) or volume-matched placebo (n = 120).

“The treatment period consisted of an initial 4-week insulin stabilization period followed by a 36-week insulin titration period,” while patients administered their assigned doses used single-dose pens, the researchers said.

Of the 475 patients enrolled in the study, 451 (94.9%) completed the trial and 424 (89.3%) completed the study treatment, with adverse events, withdrawal by patients, and protocol deviation serving as the main reasons for treatment discontinuation.

At baseline, the mean patient age was 61, mean patient body mass index was 33.4, and mean duration of diabetes was 13.3 years. Enrollment began in August of 2019 and follow-up was completed in January of 2021.

Analyses revealed:

  • Treatment was prematurely discontinued by 10% of participants in the 5-mg tirzepatide group, 12% in the 10-mg tirzepatide group, 18% in the 15-mg tirzepatide group, and 3% in the placebo group
  • At week 40, mean A1C change from baseline was −2.40% with 10-mg tirzepatide and −2.34% with 15-mg tirzepatide vs −0.86% with placebo (10 mg: difference vs placebo, −1.53%; 97.5% CI, −1.80% to −1.27%; 15 mg: difference vs placebo, −1.47%; 97.5% CI, −1.75% to −1.20%; P < .001 for both)
  • Mean A1C change from baseline was −2.11% with 5-mg tirzepatide (difference vs placebo, −1.24%; 95% CI, −1.48% to −1.01%; P < .001)
  • Mean body weight change from baseline was −5.4 kg with 5-mg tirzepatide, −7.5 kg with 10-mg tirzepatide, −8.8 kg with 15-mg tirzepatide and 1.6 kg with placebo
  • Higher percentages of patients treated with tirzepatide vs those treated with placebo had A1C less than 7% (85%-90% vs 34%; P < .001 for all)
  • All doses of tirzepatide were associated with statistically significant improvements from baseline in total cholesterol, low-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, and triglycerides at week 40

Diarrhea, nausea, and vomiting were the most common treatment-emergent adverse events in the groups receiving tirzepatide; however, incidence of new events decreased over time in these groups and no deaths were recorded during the study.

In addition, “3 episodes of severe hypoglycemia were reported in 3 patients: 2 in the 10-mg tirzepatide group and 1 in the 15-mg tirzepatide group,” authors wrote. Overall, the adverse event profile recorded in the current analysis is consistent with previous research on tirzepatide and other GLP-1 receptor agonists, they added.

Eli Lilly has submitted SURPASS-5 as part of tirzepatide’s submission for regulatory review, and the treatment is currently undergoing evaluation for patients with T2D in the United States, Japan, Europe and other countries.

Throughout the study “there was no proactive insulin dose reduction implemented in response to meeting or approaching a glycemic target, and therefore further research is warranted to explore whether this approach could result in substantial insulin sparing while providing adequate glycemic control and potentially reducing hypoglycemia risk,” the authors added.

Participants self-reported gastrointestinal adverse events, marking a limitation to the study. The researchers also cautioned results may not be generalizable to other treatment regimens using different oral antihyperglycemic medications outside of insulin glargine with or without metformin.

“Due to the global nature of the study and the countries participating in it, the percentage of participants identifying as certain racial or ethnic groups was low,” the researchers said.


Dahl D, Onishi Y, Norwood P, et al. Effect of subcutaneous tirzepatide vs placebo added to titrated insulin glargine on glycemic control in patients with type 2 diabetes. JAMA. Published online February 8, 2022. doi:10.1001/jama.2022.0078

Related Videos
Zachary Cox, PharmD
lisa kottschade
dr erin gillaspie
Related Content
© 2023 MJH Life Sciences
All rights reserved.