Tirzepatide bests insulin degludec for achieving blood sugar targets in type 2 diabetes: Lancet

USA: Once-weekly treatment with tirzepatide compared to insulin degludec led to superior glycemic control in patients with type 2 diabetes (T2D) on metformin, with or without an SGLT2 inhibitor, says a recent study published in The Lancet Diabetes & Endocrinology.

The findings provide additional evidence to the effect and potential of tirzepatide for achieving glycemic targets without increasing hypoglycemia risk versus basal insulin. 

Tirzepatide, a novel dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist, is under development for type 2 diabetes treatment. In the study, Katelyn Brown, Eli Lilly and Company, Indianapolis, IN, USA, and colleagues aimed to compare the 24 h glucose profile of participants given tirzepatide compared with those who were given insulin degludec using continuous glucose monitoring (CGM).

For this purpose, the researchers performed a substudy of the open-label, parallel-group, phase 3 SURPASS-3 trial at 45 sites across six countries. Eligible participants in the main study were adults with type 2 diabetes, a baseline HbA1c of 7·0–10·5% (53–91 mmol/mol), and a BMI of 25 kg/m2 or more, who were insulin-naive, and treated with metformin alone or in combination with an SGLT2 inhibitor for at least 3 months before screening.

People in the main study were randomly assigned in the ratio of 1:1:1:1 to receive a once-weekly subcutaneous injection of tirzepatide 5 mg, 10 mg, or 15 mg, or a once-daily subcutaneous injection of titrated insulin degludec (100 U/mL). 

The substudy enrolled a subset of these patients with a normal wake-sleep cycle, and interstitial glucose values were collected by CGM for approximately 7 days at baseline, 24 weeks, and 52 weeks. 

The primary outcome compared pooled participants assigned to 10 mg and 15 mg tirzepatide versus insulin degludec for the proportion of time that CGM values were in the tight target range (71 - 140 mg/dL) at 52 weeks. The secondary outcome compared tirzepatide (5 mg, 10 mg, and 15 mg) versus insulin degludec for the proportion and duration of time in the tight target range at 24 and 52 weeks.

313 participants were screened for eligibility from April 1 to Nov 27, 2019, 243 of whom were enrolled in CGM substudy (tirzepatide 5 mg, n=64; tirzepatide 10 mg, n=51; tirzepatide 15 mg, n=73; and insulin degludec, n=55). 

"Once-weekly treatment with tirzepatide showed superior glycaemic control measured using CGM versus insulin degludec in people with type 2 diabetes on metformin, with or without an SGLT2 inhibitor," wrote the authors. 

"Findings provide additional evidence of the effect of tirzepatide and the potential for achieving blood sugar targets without an increase of hypoglycaemic risk compared with basal insulin," they concluded.

Reference:

The study titled, "Efficacy of once-weekly tirzepatide versus once-daily insulin degludec on glycaemic control measured by continuous glucose monitoring in adults with type 2 diabetes (SURPASS-3 CGM): a substudy of the randomised, open-label, parallel-group, phase 3 SURPASS-3 trial," was published in The Lancet Diabetes & Endocrinology.

DOI: https://doi.org/10.1016/S2213-8587(22)00077-8