Lilly's tirzepatide significantly cuts blood glucose, weight in two more trials

Eli Lilly reported top-line data Wednesday demonstrating that its once-weekly GIP/GLP-1 receptor agonist tirzepatide met the primary and key secondary endpoints at all dose levels in the Phase III SURPASS-3 and SURPASS-5 studies. Mike Mason, president of Lilly Diabetes, said "tirzepatide delivered impressive HbA1c and body weight reductions in both studies and continued to achieve consistent efficacy and safety results in people living with type 2 diabetes, regardless of how long they have had the condition."

The latest results follow positive late-stage data unveiled in December when Eli Lilly announced that tirzepatide was superior to placebo at lowering blood glucose and body weight in adults with type 2 diabetes in the SURPASS-1 trial (for related analysis, see ViewPoints: Novo Nordisk's semaglutide braces for tirzepatide impact).

SURPASS-3 enrolled 1444 insulin-naïve patients with type 2 diabetes who had inadequate glycaemic control on stable doses of metformin, with or without an SGLT-2 inhibitor. Participants had type 2 diabetes for an average 8.4 years, and were randomised to one of three doses of tirzepatide or Novo Nordisk's Tresiba (insulin degludec) over a period of 52 weeks. Meanwhile, in the 40-week SURPASS-5 study, 475 participants were randomly assigned to one of the three tirzepatide doses or placebo, as add-on to insulin glargine, with or without metformin. Patients in the trial had had diabetes for an average of 13.3 years.

Largely dose-dependent benefits

SURPASS-3 participants had a baseline HbA1c of 8.17% and weighed 94.3 kg on average. Eli Lilly said all three doses were superior to Tresiba on both A1C and body weight reductions. Using the efficacy estimand, results showed that at the highest dose of 15 mg, tirzepatide lowered HbA1c by 2.37% and patients lost 12.9 kg, or 13.9% of their body weight. By contrast, those given Tresiba saw their blood glucose levels fall by 1.34%, while they gained 2.3 kg, or 2.7% in body weight.

Eli Lilly noted that across the three doses, up to 92.6% of participants on tirzepatide achieved HbA1c of less than 7%, while as many as 48.4% achieved a level less than 5.7%. Fewer people in the Tresiba group managed to meet these targets, at 61.3% and 5.4%, respectively.

Similarly, in SURPASS-5, all three doses of tirzepatide were superior to placebo in terms of HbA1c and weight reductions. Tirzepatide 15 mg led to a 2.59% decrease in HbA1c levels from a baseline of 8.31%, with patients losing an average 10.9 kg, or 11.6% of their body weight, from the mean 95.2 kg they weighed at the start of the study. The placebo group saw blood sugar levels fall 0.93%, while patients gained 1.7 kg in weight.

Moreover, up to 97.4% of SURPASS-5 participants treated with tirzepatide achieved an HbA1c of less than 7%, although in this case, the greatest effect was seen in the middle dose group. It was 94% for tirzepatide 15 mg and 33.9% for placebo. In addition, up to 62.4% of tirzepatide-treated participants achieved a HbA1c of less than 5.7%, compared with only 2.5% for placebo.

Full registration study readouts this year

In both studies, Eli Lilly said the overall safety profile of tirzepatide was "similar to that of the well-established GLP-1 receptor agonist class," with gastrointestinal side effects being the most commonly reported adverse events, which decreased with continued dosing.

According to Eli Lilly, the SURPASS development programme for tirzepatide has enrolled more than 13,000 people with type 2 diabetes across 10 clinical trials, five of which are global registration studies. It added that full results from the registration studies are anticipated this year. The company is also running the Phase III SURPASS-CVOT cardiovascular outcomes study that got under way last June to assess tirzepatide head-to-head against its GLP-1 receptor agonist Trulicity (dulaglutide). For additional analysis, see KOL Views Q&A: Expert opinion on data from Lilly's SURPASS-1 trial of tirzepatide.

Eli Lilly is also investigating tirzepatide as a potential treatment for non-alcoholic steatohepatitis.

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