Lilly’s SURPASS-2 results now published
Tirzepatide achieved superior HbA1C and impressive weight loss results compared to injectable semaglutide in adults with type 2 diabetes, new research reports.
All three doses of tirzepatide achieved superior HbA1C and weight reductions compared to semaglutide 1 mg in data simultaneously presented at the American Diabetes Association’s 81st Scientific Sessions (ADA).
Tirzepatide led to superior HbA1C and body weight reductions from baseline compared to injectable semaglutide 1 mg in 40-week results from Eli Lilly and Company’s (NYSE: LLY) SURPASS-2 clinical trial, which were presented in a late breaking poster presentation during the ADA
These results, which will also be featured during an ADA-sponsored symposium on Tuesday 29th June, showed that all three tirzepatide doses achieved greater HbA1C and weight reductions compared to semaglutide 1 mg.
Additionally, a prespecified exploratory composite endpoint comprised of participants who achieved an HbA1C level less than or equal to 6.5 percent and weight loss of 10 percent or greater, while not experiencing hypoglycaemia less than 54 mg/dL (3 mmol/L) or severe hypoglycaemia, was evaluated.
Across the three doses of tirzepatide, 32 percent (5 mg), 51 percent (10 mg) and 60 percent (15 mg) of participants achieved this composite endpoint compared to 22 percent of participants taking semaglutide 1 mg.1,2
NIHR Senior Investigator Emeritus and Principal Investigator of SURPASS-2., Professor Melanie Davies said: “In SURPASS-2, tirzepatide delivered clinically meaningful efficacy, and superior HbA1C and weight reductions compared to semaglutide 1 mg.
“Head-to-head data like these are very exciting, and underscore that, if approved, tirzepatide may be a promising new treatment option for people with type 2 diabetes here in the UK.”
The overall safety profile of tirzepatide was similar to the well-established glucagon-like peptide-1 (GLP-1) receptor agonist class.
Across all treatment arms, the most commonly reported adverse events were gastrointestinal-related.
Tirzepatide is a novel investigational once-weekly dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist that integrates the actions of both incretins into a single molecule, representing a new class of medicines being studied for the treatment of type 2 diabetes.
Injectable semaglutide 1 mg is a GLP-1 receptor agonist and the highest dose of injectable semaglutide approved by the EMA for the treatment of type 2 diabetes.
Dr Kunal Gulati, Senior Medical Lead Diabetes, Lilly Northern Europe, said: “These data suggest that tirzepatide has the potential to be a new treatment option to help people with type 2 diabetes better manage HbA1C and weight.
“As a leader in diabetes care, Lilly is proud to be researching and developing solutions that can lead to meaningful HbA1C reductions and weight loss to help meet the needs of people with type 2 diabetes.”
SURPASS-2 was a 40-week, randomised, open-label trial comparing the efficacy and safety of tirzepatide to semaglutide as an add-on to metformin in adults with type 2 diabetes.
The study randomised 1,879 participants, who had a mean duration of diabetes of 8.6 years, a baseline HbA1C of 8.28 percent and a baseline weight of 93.7 kg.
For both estimands, all three doses of tirzepatide demonstrated superior HbA1C and body weight reductions compared to semaglutide 1 mg. Specifically, the efficacy estimand results showed:
- HbA1C reduction: -2.09% (5 mg), -2.37% (10 mg), -2.46% (15 mg), -1.86% (semaglutide 1 mg)
- Weight reduction: -7.8 kg (5 mg), -10.3 kg (10 mg), -12.4 kg (15 mg), -6.2 kg (semaglutide 1 mg)
- Percent of participants achieving HbA1C <7%: 85% (5 mg), 89% (10 mg), 92% (15 mg), 81% (semaglutide 1 mg)
- Percent of participants achieving HbA1C <5.7%: 29% (5 mg, not controlled for type 1 error), 45% (10 mg), 51% (15 mg), 20% (semaglutide 1 mg)
For the treatment-regimen estimand, all three doses of tirzepatide delivered superior HbA1C and body weight reductions compared to semaglutide 1 mg.
Greater percentages of participants achieved an HbA1C of less than 7 percent across all three doses compared to semaglutide 1 mg, with statistical significance met for 10 mg and 15 mg but not for 5 mg. Specifically:
- HbA1C reduction: -2.01% (5 mg), -2.24% (10 mg), -2.30% (15 mg), -1.86% (semaglutide 1 mg)
- Weight reduction: -7.6 kg (5 mg), -9.3 kg (10 mg), -11.2 kg (15 mg), -5.7 kg (semaglutide 1 mg)
- Percent of participants achieving HbA1C <7%: 82% (5 mg), 86% (10 mg), 86% (15 mg), 79% (semaglutide 1 mg)
- Percent of participants achieving HbA1C <5.7%: 27% (5 mg), 40% (10 mg), 46% (15 mg), 19% (semaglutide 1 mg)
Hypoglycaemia less than 3 mmol/L (clinically significant hypoglycaemia) was reported in 0.6 percent (5 mg), 0.2 percent (10 mg) and 1.7 percent (15 mg) of participants in the tirzepatide arms and in 0.4 percent of participants in the semaglutide 1 mg arm.
In an additional exploratory endpoint, all three doses of tirzepatide led to favourable changes from baseline in fasting lipids.
Specifically, at the highest dose of tirzepatide (15 mg): triglycerides were reduced by 24.8 percent, very low-density lipoprotein (VLDL) cholesterol was reduced by 23.7 percent, and high-density lipoprotein (HDL) cholesterol was increased by 7.1 percent.2
The most commonly reported adverse events across all treatment arms were gastrointestinal-related and mostly mild-to-moderate, including nausea (17.4 percent [5 mg], 19.2 percent [10 mg], 22.1 percent [15 mg], 17.9 percent [semaglutide 1 mg]), diarrhoea (13.2 percent [5 mg], 16.4 percent [10 mg], 13.8 percent [15 mg], 11.5 percent [semaglutide 1 mg]) and vomiting (5.7 percent [5 mg], 8.5 percent [10 mg], 9.8 percent [15 mg], 8.3 percent [semaglutide 1 mg]). Treatment discontinuation rates due to adverse events were 5.1 percent (5 mg), 7.7 percent (10 mg), 7.9 percent (15 mg) and 3.8 percent (semaglutide 1 mg).
SURPASS-2 is the second of five global registration studies for tirzepatide in type 2 diabetes, all of which have been completed. Lilly intends to submit the full registration package to regulatory authorities by the end of 2021.
Treatment differences for two estimands – efficacy and treatment-regimen – were evaluated for three tirzepatide doses (5 mg, 10 mg and 15 mg) compared to semaglutide 1 mg.
Efficacy estimand represents efficacy prior to discontinuation of study drug or initiating rescue therapy for persistent severe hyperglycaemia.
Treatment-regimen estimand represents the efficacy irrespective of adherence to the investigational medicine or introduction of rescue therapy for persistent severe hyperglycaemia.
The entire study is now available in The New England Journal of Medicine.
To access the full set of results, click here.