In an open-label, parallel-group, phase 3 trial conducted by Eli Lilly and Company, tirzepatide more effectively reduced glycated hemoglobin (HbA1C) and bodyweight compared with once-daily insulin degludec. These findings were published in The Lancet.

Patients (N=1437) with type 2 diabetes (T2D) who were insulin-naïve, treated with metformin alone or in combination with a sodium-glucose cotransport-2 inhibitor (SGLT2) for at least three months, and had HbA1C in the range of 7.0%-10.5% were recruited from 122 centers in 13 countries between 2019 and 2021. Randomization occurred in a 1:1:1:1 ratio to receive 52 weeks of 5, 10, or 15 mg tirzepatide weekly or the titrated insulin degludec daily. Patients were assessed for glycemic control, bodyweight, and safety.

Participants were aged mean 57.4 (standard deviation [SD], 10.0) years, 44% were women and 56% were men. , The majority (91%) were White, with an overall mean HbA1C level of 8.17% (SD, 0.91%), BMI of33.5 (SD, 6.1) kg/m2, and an  average duration of diabetes of 8.4 (SD, 6.2) years.


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At 52 weeks, HbA1C had decreased from baseline by 1.34% among the insulin recipients. The patients in the 5, 10, and 15 mg tirzepatide cohorts had comparatively greater HbA1C reductions of 1.93%, 2.20%, and 2.37% (all P <.0001), respectively. The target endpoint of HbA1C <7.0% was achieved by 61% of the insulin group compared with 82% of the 5 mg (P <.0001), 90% of the 10 mg (P <.0001), and 93% of the 15 mg (P <.0001) tirzepatide recipients.

Fasting serum glucose was significantly reduced at 52 weeks among the 5 mg tirzepatide group compared with insulin (P =.0036) but not the 10 mg (P =.7510) or 15 mg (P =.1682) recipients.

The patients randomized to receive insulin had gained an average of 2.3 (SD, 0.4) kg by week 52 while those randomized to receive low, intermediate, and high tirzepatide doses had lost 7.5 (SD, 0.4), 10.7 (SD, 0.4), and 12.9 (SD, 0.4) kg (all P <.0001), respectively. The target of 5% bodyweight loss during the study was achieved by 6% of the insulin, 66% of the 5 mg, 84% of the 10 mg, and 88% of the 15 mg tirzepatide recipients.

The composite endpoint of HbA1C <7.0% without weight gain or documented hypoglycemia was associated more likely to occur among patients receiving 5 mg (odds ratio [OR], 21.48; 95% CI, 14.35-32.16; P <.0001), 10 mg (OR, 42.47; 95% CI, 27.06-66.66; P <.0001), and 15 mg (OR, 60.38; 95% CI, 37.31-97.71; P <.0001) tirzepatide.

Adverse events leading to treatment discontinuation occurred among 7%, 10%, and 11%, of the low, intermediate, and high tirzepatide groups compared with 1% of the insulin cohort. Serious adverse events were similar among the tirzepatide (8%, 6%, 7%) and insulin (6%) recipients.

This study was limited by the open-label design and the differing dosing frequency between study drugs.

These data, according to the researchers, indicated that tirzepatide outperformed titrated insulin degludec with regards to glycemic control and weight loss after 52 weeks of therapy among insulin-naïve patients with T2D.

Disclosure: The study was funded by Eli Lilly, which manufactures tirzepatide. Multiple authors declared affiliations with pharmaceutical companies.  Please refer to the original article for a full list of disclosures.

Reference

Ludvik B, Giorgino F, Jódar E, et al. Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes (SURPASS-3): a randomised, open-label, parallel-group, phase 3 trial. Lancet. 2021;398(10300):583-598. doi:10.1016/S0140-6736(21)01443-4