Eli Lilly’s tirzepatide has significantly reduced blood sugar and body weight in Type 2 diabetics in a late-phase clinical trial. The release of the top-line data provides early validation of Lilly’s decision to place a big bet on the dual GIP/GLP-1 agonist.
Investigators randomized 478 Type 2 diabetics to receive one of three doses of tirzepatide or placebo once a week for 40 weeks. At the end of that time, A1C, a measure of blood sugar, had fallen 2.07% from a baseline of 7.9% in the high-dose tirzepatide cohort. A1C in the placebo arm rose 0.04%. The clinical trial linked the two lower doses of tirzepatide to A1C reductions of close to 1.9%.
A similar pattern played out across the secondary endpoints, with all tirzepatide doses, but typically particularly the high dose, beating placebo. The weight of participants on the high dose of tirzepatide fell 9.5 kg, an 11% reduction from baseline, versus a 0.7 kg drop in the placebo cohort. The results are in line with the findings of an earlier phase 2b trial.
In the high-dose arm, 87.9% of patients had an A1C of less than 7% by the end of the trial, compared to 19.6% of people in the control group. Almost 52% of patients on the high dose of tirzepatide had an A1C of less than 5.7%, the threshold of normal. Less than 1% of patients on placebo had an A1C of less than 5.7%.
Lilly achieved those results in patients who were naïve to diabetes injectable therapies and had not used oral antihyperglycemic medications in the three months prior to screening. Participants had a baseline A1C between 7.0% and 9.5% and were diagnosed with Type 2 diabetes 4.7 years before the start of the trial, on average.
The safety profile of tirzepatide in the phase 3 was similar to those of GLP-1 receptor agonists such as Lilly’s own Trulicity and Novo Nordisk’s Ozempic. Most adverse events were gastrointestinal-related and mild to moderate in severity. The discontinuation rate in the high-dose arm was 21.5%, versus less than 10% in the two lower-dose cohorts, but Lilly said most of the dropouts were due to the pandemic and family or work reasons. The dropout rate in the placebo group was 14.8%.
Delivering top-line data from the trial, SURPASS-1, is the first in a series of milestones that will shape the ability of Lilly to disrupt the diabetes market using tirzepatide. Lilly is running nine other phase 3 clinical trials of the drug, including a mammoth, 12,500-subject cardiovascular outcome trial that got underway early this year. A series of data drops are scheduled for the next few years.
Lilly could emerge from the phase 3 program with a drug that protects it from the anticipated loss of patent protection on Trulicity in 2027 and provides a real threat to its rivals for the diabetes space, notably Novo. The reductions in A1C and body weight seen in SURPASS-1 exceeded those achieved by Novo’s Ozempic and Rybelsus, although such cross-trial comparisons can be unreliable. Analysts at Jefferies think the readout could have been worse for Novo.
"In our view the efficacy looks competitive and the safety acceptable, albeit gastrointestinal adverse event rates remain slightly higher than those for marketed GLP-1s. Tirzepatide looks like it will provide competition for Ozempic but does not seem vastly superior, in our view, avoiding the "worst case" scenario for Novo Nordisk," the analysts wrote in a note to investors.