medwireNews: People with type 2 diabetes on metformin monotherapy have greater glycemic control improvement and weight reduction with tirzepatide than semaglutide, report the SURPASS-2 investigators.
During 40 weeks of treatment, glycated hemoglobin (HbA1c) levels fell by an average of 2.01, 2.24, and 2.30 percentage points in trial participants randomly assigned to take tirzepatide at weekly doses of 5, 10, and 15 mg, respectively, compared with an average 1.86 percentage points in those taking semaglutide 1 mg.
The results were presented at the virtual ADA 81st Scientific Sessions and simultaneously published in The New England Journal of Medicine, along with an editorial by Katherine Tuttle (University of Washington, Seattle, USA). She writes that the emergence of the dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist “takes incretin therapeutic agents to a new level.”
Juan Pablo Frías explains the significance of the SURPASS-2 findings, in which the dual agonist tirzepatide provided superior glycemic control and weight loss to semaglutide (5:44).
The average baseline HbA1c level was 8.28% (67.03 mmol/mol). The 1878 trial participants were an average age of 56.6 years and had an average diabetes duration of 8.6 years. All were taking metformin but no other diabetes medications. By the end of the trial, 82–86% of participants given tirzepatide had achieved an HbA1c level below 7.0% (53 mmol/mol), as had 79% of those given semaglutide.
The corresponding proportions of people achieving HbA1c below 5.7% (39 mmol/mol) were 27–46% and 19%.
Juan Frías (National Research Institute, Los Angeles, USA) and co-researchers also report dose-dependent weight reductions among the participants taking tirzepatide, who lost an average of 7.6, 9.3, and 11.2 kg with the 5, 10, and 15 mg doses, respectively, compared with an average 5.7 kg reduction with semaglutide.
In her editorial, Tuttle highlighted the “impressive” effect of tirzepatide on bodyweight, noting that bodyweight was still falling in the 15 mg group after 40 weeks of treatment. “Given the driving force of obesity in the epidemic of diabetes, as well as in the risks of cardiovascular and chronic kidney disease, this observation may lead to consideration of the use of tirzepatide for weight loss,” she says.
However, she cautions that the investigators used the currently licensed semaglutide dose of 1 mg as a comparator, whereas in the recently published STEP 2 trial a dose of 2.4 mg resulted in an average weight loss of 9.7 kg.
“Therefore, the doses of tirzepatide and semaglutide were not comparable in terms of weight outcomes in the current trial,” says Tuttle.
Rates of clinically significant hypoglycemia (blood glucose <54 mg/dL; 3.0 mmol/L) were overall low, at 0.2–1.7% in the tirzepatide groups and 0.4% in the semaglutide group. As expected, nausea (17–22 vs 18%) and diarrhea (13–16 vs 12%) were the most frequent adverse events.
Most gastrointestinal events occurred during the dose-escalation period; all participants started tirzepatide at 2.5 mg/week, escalating to the target dose over 4 to 20 weeks.
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ADA Scientific Sessions; 25–29 June 2021
N Engl J Med 2021; doi:10.1056/NEJMoa2107519
N Engl J Med 2021; doi:10.1056/NEJMe2109957