Latest type 2 diabetes drug achieves blood sugar and weight targets faster

The phase 3 SURPASS trials published in 2021 established that tirzepatide lowers blood sugar and supports weight loss better than other drugs for type 2 diabetes (T2D) [1]. Now new research evaluating the time taken to reach blood glucose targets indicates that tirzepatide also achieves blood sugar control and weight-loss goals faster than existing diabetes drugs.

The latest analyses of the SURPASS-2 and SURPASS-3 trials, being presented at this year’s European Association for the Study of Diabetes (EASD) Annual Meeting in Stockholm, Sweden (19-23 Sept), found that adults treated with various doses of injectable tirzepatide (5, 10, and 15 mg) reached blood glucose targets about four weeks sooner than those taking injectable semaglutide (1 mg), and between four and 12 weeks sooner than those taking a once-daily insulin (degludec; iDeg), along with diet and exercise and oral glucose-lowering medications.

“Tirzepatide is unique because it mimics two natural insulin-releasing and appetite-suppressing hormones in one injection”, says lead author Dr Adie Viljoen, a Consultant Metabolic Physician and Chemical Pathologist from the East and North Hertfordshire NHS Trust, UK.“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. But it is important to remember that these medications should be used in addition to diet and exercise.”

T2D is a chronic and progressive condition in which the body does not make or use insulin normally, leading to high levels of glucose in the blood. More than 30 million Americans have T2D, but despite the availability of many medications to treat diabetes, only around half of US adults with T2D achieve target haemoglobin A1c (HbA1c; a measure of blood sugar control) of less than 7% [2]. Higher HbA1c levels are associated with complications like heart disease, stroke, kidney disease (nephropathy), eye disease (retinopathy) and nerve disease (neuropathy).

Tirzepatide is a single molecule that belongs to a new class of diabetes drugs that mimics two hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), involved in blood sugar control and appetite suppression. It was approved for the treatment of T2D by the US Food and Drug Administration in May 2022.

The SURPASS-2 and SURPASS-3 trials compared different doses of tirzepatide (5, 10, and 15 mg) with a once-weekly injectable semaglutide 1 mg (which is a single hormone, GLP-1  mimic agent) as an add-on therapy to metformin, or a long-acting insulin (iDeg), as an add-on therapy to metformin with or without a sodium-glucose cotransporter-2 inhibitor, respectively [3].

On average, participants treated with all doses of tirzepatide lowered their HbA1c more than those treated with semaglutide and iDeg, and a greater proportion achieved a HbA1c of less than 7% (<53 mmol/mol), less than or equal to 6.5% (≤48 mmol/mol), and less than 5.7% (<39 mmol/mol) at 40-weeks (SURPASS-2) and 52-weeks (SURPASS-3), respectively.

In this latest analysis comparing the time to reach HbA1c targets from the start of the study, researchers found that participants taking tirzepatide reached HbA1c targets of less than 7% and 6.5% or less considerably faster than both semaglutide and iDeg (see table in notes to editors).

The average (median) time to achieve a HbA1c level of less than 7% was around 8 weeks for all tirzepatide doses compared to 12 weeks for both semaglutide and iDeg; and to reach 6.5% or less was 12 weeks versus about 16 weeks and 24 weeks, respectively.

Further analyses of SURPASS-2, found that participants treated with tirzepatide also reached weight-loss goals significantly faster than semaglutide. The average time to reach 5% or more weight loss was around 12 weeks on the two higher doses of tirzepatide (10 and 15 mg) compared to 24 weeks for semaglutide (see table in notes to editors).

“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”, says Viljoen. “For people with type 2 diabetes to be able to achieve these improvements in health in around half the time is pretty incredible.”

Mild to moderate gastrointestinal adverse events such as nausea, vomiting, and diarrhoea were noted in participants taking tirzepatide and were most frequently reported during the dose escalation period and decreased over time.

The authors acknowledge several limitations of the study, including that the studies were not specifically designed to compare the rate of glycaemic control and weight loss and therefore these analyses should be interpreted with caution.

For interviews with the report authors, please contact Dr Adie Viljoen, East and North Hertfordshire NHS Trust, UK E) adie.viljoen@nhs.net T) +44 (0)7988 016 781

Alternative contact in the EASD Press Room: Tony Kirby T) + 44(0)7834 385827 E) tony@tonykirby.com

This study was funded by Eli Lilly and Company.

The authors have received grants from Sanofi and lecture/other fees from Novartis, Boehringer Ingelheim, and Napp. Non-financial support has also been provided by Lilly, Novo Nordisk, and AstraZeneca.

Twitter (for when embargo lifts): @EASDnews

Notes to editors:

[1] https://www.nejm.org/doi/pdf/10.1056/NEJMoa2107519
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 - The Lancet
[2] Public Health Implications of Recommendations to Individualize Glycemic Targets in Adults With Diabetes (nih.gov)
[3] In SURPASS-2 and 3, tirzepatide was initiated at a dose of 2.5 mg once weekly, and the doses were increased by 2.5 mg every 4 weeks until the randomly assigned dose was reached and maintained for the duration of the trial. Semaglutide was initiated at a dose of 0.25 mg once weekly, and the dose was doubled every 4 weeks until 1 mg was reached and maintained for the duration of the trial. Insulin degludec was initiated at 10 U/day and titrated weekly to a fasting blood glucose of <5.0 mmol/L following a treat-to-target algorithm.

This press release is based on abstract 591 at The European Association for the Study of Diabetes (EASD). All accepted abstracts have been extensively peer reviewed by the congress selection committee. There is no full paper at this stage, but the authors are happy to answer your questions. The research has not yet been submitted to a medical journal for publication. As this is an oral presentation there is no poster available.

Table: Summary of time to reach HbA1c targets and weight loss thresholds