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SURPASS-2: tirzepatide vs. semaglutide

SURPASS-2: tirzepatide vs. semaglutide

Results from the open-label, randomised SURPASS-2 trial, assessing the novel dual GIP (glucose-dependent insulinotropic polypeptide)/GLP-1 (glucagon-like peptide 1) receptor agonist tirzepatide vs. human GLP-1 receptor agonist semaglutide in 1,878 type 2 diabetes patients inadequately controlled with metformin, conferred statistically significant HbA1c and body weight reductions from baseline compared to semaglutide in all three treatment arms (tirzepatide 5 mg, 10 mg, and 15 mg).

At 40 weeks, all once-weekly tirzepatide doses were found to be noninferior and superior to semaglutide 1 mg once weekly with respect to the mean change in HbA1c level from baseline, the primary outcome, delivering HbA1c reductions of -2.01% (5 mg), -2.24% (10 mg), and -2.30% (15 mg) vs. -1.86% with semaglutide.

Mean reductions in body weight at 40 weeks were greater with tirzepatide compared with semaglutide and were dose-dependent, with 5 mg, 10 mg and 15 mg tirzepatide doses resulting in mean body weight reductions of 7.6 kg, 9.3 kg and 11.2 kg, respectively, compared with 5.7 kg with semaglutide.

Pre-specified exploratory analyses assessed the proportion of patients achieving an HbA1c ≤ 6.5% and weight loss of 10% or greater, without experiencing clinically significant hypoglycaemia (blood glucose < 54 mg/dL) or severe hypoglycaemia to be 32%-60% in the tirzepatide arms vs 22% on semaglutide 1 mg.

Consistent with adverse events expected with the GLP-1 receptor agonist class, the most common adverse events reported in the trial were mild to moderate gastrointestinal events including nausea, 17 to 22% in tirzepatide groups and 18% in semaglutide group; diarrhoea 13 to 16% and 12%; and vomiting, 6 to 10% and 8% respectively.

A total of 13 deaths (0.7%) occurred in the total population during the trial (4 patients in each of the three tirzepatide groups and 1 patient in the semaglutide group). 5 deaths were related to COVID-19, and a 6th suspected.

Prescribing information for Invokana (canagliflozin)

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Editorial Board

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Dr. Salvatore A. De Cosmo's image

Dr. Salvatore A. De Cosmo

Head of Unit of Internal Medicine and Endocrinology, Scientific Institute “Casa Sollievo della Sofferenza” San Giovanni, Rotondo, Italy
,
Image
Dr. Juan José Gorgojo Martínez's image

Dr. Juan José Gorgojo Martínez

Head of Department of Endocrinology and Nutrition, University Hospital Fundación, Alcorcon, Madrid, Spain
,
Image
Dr. Patrick Holmes' image

Dr. Patrick Holmes

General Practitioner, St. George's Medical Practice, Darlington, UK

Editorial Board

Image
Dr. Salvatore A. De Cosmo's image

Dr. Salvatore A. De Cosmo

Head of Unit of Internal Medicine and Endocrinology, Scientific Institute “Casa Sollievo della Sofferenza” San Giovanni, Rotondo, Italy
Image
Dr. Juan José Gorgojo Martínez's image

Dr. Juan José Gorgojo Martínez

Head of Department of Endocrinology and Nutrition, University Hospital Fundación, Alcorcon, Madrid, Spain
Image
Dr. Patrick Holmes' image

Dr. Patrick Holmes

General Practitioner, St. George's Medical Practice, Darlington, UK

Publication under Spotlight

Tirzepatide Versus Semaglutide Once Weekly in Patients With Type 2 Diabetes

N Engl J Med
2021;385(6):503-515

Authors: Juan P Frias, Melanie J Davies, Julio Rosenstock, Federico C Perez Manghi, Laura Fernández Lando, Brandon K Bergman, Bing Liu, Xuewei Cui and Katelyn Brown

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