Tolerability remains key for tirzepatide

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Today’s data from the first of the trials in the vast Surpass programme to have compared Lilly’s tirzepatide with an active control are encouraging, but lack of gastrointestinal tolerability remains a drag on the GIP/GLP-1 agonist. In Surpass-3 tirzepatide 15mg, the highest dose, showed statistically significant improvements over Tresiba at one year in both blood sugar and weight. But nausea, diarrhoea and vomiting were seen respectively in 24%, 16% and 10% of patients given the same dose. Tolerability was only slightly better than in Surpass-5, which compared tirzepatide with placebo against a background of Basaglar, and also met all its endpoints. Novo’s GLP-1s are not clean on safety either, with rates of nausea almost as high as tirzepatide’s. Still, the sellside seems to favour Novo judging by EvaluatePharma’s consensus sales forecasts for tirzepatide, which remain some way behind those for Ozempic and Rybelsus.

Cross-trial comparison of tirzepatide and Novo's GLP-1 agonists
Project Tirzepatide* Tirzepatide* Tirzepatide* Ozempic Rybelsus
Company Lilly Lilly Lilly Novo Nordisk
Trial Surpass-1 Surpass-3 Surpass-5 - -
A1c reduction (%) 1.69-1.75 1.85-2.14 2.11-2.40 1.4-1.6 1.2-1.4
% of pts achieving A1c <7 78-85 79-84 85-90 70-73 69-77
Placebo-adjusted weight loss (kg) 5.3-6.8  8.9-13.2 7.0-10.4 2.6-3.5 0.9-2.3
Nausea (%) 12-18 12-24 13-18 16-20 11-20
Diarrhoea (%) 12-14 15-17 12-21 ~8 9-10
Vomiting (%) 3-6 6-10 7-13 5-9 6-8
*Treatment-regimen estimands. Source: Lilly releases & product labels.

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