Tirzepatide Superior to Insulin Degludec in Achieving T2D Glycemic Targets

Katelyn Brown, PharmD

New findings suggest once-weekly treatment with tirzepatide resulted in superior glycemic control compared to insulin degludec in participants with type 2 diabetes (T2D) on metformin, with or without a sodium-glucose co-transporter 2 (SGLT2) inhibitors.

Study data show Individuals given once-weekly tirzepatide had a greater proportion of time in tight target range compared with patients given insulin degludec.

“These new data provide additional evidence to the effect of tirzepatide and potential for achieving glycemic targets without increase of hypoglycemic risk compared with a basal insulin,” wrote study author Katelyn Brown, PharmD, Lilly Corporate Center.

Brown and colleagues used continuous glucose monitoring (CGM) to compare the 24 hour glucose profile for participants given tirzepatide compared with those given insulin degludec. The substudy of the open-label, phase 3 SURPASS-3 trial was done at 45 sites across 6 countries.

Eligible patients were adults with T2D, 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 a SGLT2 inhibitor for ≥3 months before screening.

Participants in the main study were randomized to receive once-weekly subcutaneous injection of tirzepatide 5 mg, 10 mg, or 15 mg, or once-daily subcutaneous injection of titrated insulin degludec (100 U/mL).

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 tight target range at 24 and 52 weeks.

From April to November 2019, a total of 313 participants were screened for eligibility. Of this number, 243 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).

Those in the pooled once-weekly tirzepatide group had a greater proportion of time in tight target range compared with patients given insulin degludec (estimated treatment difference, 25% [95% CI, 16 - 33]; P <.0001).

Additionally, participants assigned to tirzepatide spent significantly more time in tight target range at 52 weeks compared with those assigned to insulin degludec (5 mg, 12% [95% CI, 1 - 22], P = .031; 10 mg, 24% [95% CI, 13 - 35], P <.0001; and 15 mg, 25% [95% CI, 14 - 35]; P <.001).

Investigators also observed participants in the tirzepatide 10 mg and 15 mg groups, but not the tirzepatide 5 mg group, spent significantly more time in tight target range at 24 weeks compared with insulin degludec (10 mg, 19% [95% CI, 8 - 30], P = .0008; 15 mg, 21% [95% CI, 11 - 31], P <.0001).

The study, “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.