Tirzepatide Reduces Time to HbA1c Targets by Up to 3 Months vs Semaglutide, Insulin Degludec

Tirzepatide (Mounjaro, Eli Lilly) was associated with more rapid achievement of glycemic targets and weight loss goals in patients with type 2 diabetes (T2D) than either semaglutide or titrated insulin degludec (iDeg) in a new analysis of data from the landmark SURPASS clinical trial program.

The findings, presented as an abstract at the European Association for the Study of Diabetes (EASD) Annual Meeting, demonstrated that adults with T2D treated with the novel once weekly dual GIP/GLP-1 mimetic reached glycemic targets 4 to 12 weeks sooner than those receiving semaglutide 1 mg and long-acting iDeg. Further, according to the study abstract, tirzepatide treated patients lost 5% of baseline bodyweight significantly faster than those treated with semaglutide. The abstract was published simultaneously in the journal Diabetologia.

“Tirzepatide is unique because it mimics two natural insulin-releasing and appetite-suppressing hormones in one injection,” said lead investigator Adie Viljoen, MD, a consultant metabolic physician and chemical pathologist from the East and North Hertfordshire NHS Trust in the United Kingdom, in an EASD statement. “The speed we are seeing in glucose-lowering and weight loss is beyond anything else we have available right now and it may put adults with type 2 diabetes in a better position for preventing long-term complications.” Keep in mind, Viljoen added, that medications of this type do not work alone and are indicated for use as adjuncts to diet and exercise.

The US Food and Drug Administration approved tirzepatide in May 2022 for the treatment of T2D based on 5 studies comprising Lilly’s phase 3 SURPASS clinical trial program. SURPASS trials compared the glucose-lowering efficacy of tirzepatide against other antihyperglycemic drug classes, and at different dosages as both monotherapy and in combination with comparator agents. The dual incretin receptor agonist proved superior in lowering HbA1c in all trials.

The new study, a preplanned exploratory analysis, evaluated data from the SURPASS-2 and -3 trials (see sidebar) to assess time to achieve glycemic targets.

Viljoen and colleagues found in this analysis that tirzepatide-treated patients reached HbA1c levels of both ≤7% and ≤6.5 significantly faster than those treated with either semaglutide or iDeg.

They report that the median time to achieve an HbA1c ≤7% was 8.1 weeks across all tirzepatide doses compared with 12 weeks for semaglutide and 12.1 weeks for titrated insulin degludec.

Time to reach HbA1c of ≤6.5% was 12.1 weeks for all tirzepatide-treated participants compared with 15.7 weeks for those taking semaglutide and 24.1 weeks for iDeg-treated patients.

The investigators also found that tirzepatide outperformed semaglutide 1.0 mg in time to achieve ≥5% weight loss, with tirzepatide 10- and 15-mg treatment groups reaching the goal at an average of 12 weeks and semaglutide-treated patients at 24 weeks.

“Even a modest weight loss of 5% of initial body weight is associated with clinically significant improvements in weight-related health issues for many individuals”, Viljoen added in the EASD statement. “For people with type 2 diabetes to be able to achieve these improvements in health in around half the time is pretty incredible.”

Adverse GI events reported as mild to moderate in patients taking tirzepatide included nausea, vomiting, and diarrhea and were most frequently see in the dose escalation period with reduction over time.

Viljoen A, Pantalone KM, Galindo RJ, et al. Patients with type 2 diabetes reach glycaemic targets faster with tirzepatide compared to semaglutide and titrated insulin degludec. Abstract presented at: the 58th European Association for the Study of Diabetes meeting; September 19-23, 2022; Stockholm, Sweden. Abstract 591