At the 59th Annual European Association for the Study of Diabetes (EASD) 2023 meeting, a new meta-analysis has shown the superior efficacy of Eli Lilly’s dual gastro inhibitory peptide (GIP)/glucagon-like peptide-1 receptor (GLP-1R) agonist tirzepatide when compared to Novo Nordisk’s GLP-1RA semaglutide (subcutaneous).

Karagiannis and colleagues identified that there is a scarcity of randomly controlled trials (RCTs) directly comparing tirzepatide with subcutaneous (SC) semaglutide. They conducted a network meta-analysis to compare the efficacy and safety of both drugs in individuals with type 2 diabetes (T2D). The results of the meta-analysis agreed with key opinion leaders (KOLs) interviewed by GlobalData, who stated that tirzepatide has superior efficacy in both weight loss and T2D, and is therefore likely to become the leading GLP-1 marketed therapy in the next decade.

Tirzepatide will likely cause Eli Lilly to become the market leader in the GLP-1 space

The meta-analysis comprised 22 RCTs, with a total of 18,742 participants. Tirzepatide 15mg was found to be the most efficacious in reducing haemoglobin A1c (HbA1c) versus placebo (mean differences -2.00%; 95% confidence interval [CI] -2.16 to -1.84), followed by tirzepatide 10mg (-1.86%; -2.02 to -1.84) and semaglutide 2.0mg (-1.62%; 1.96 to 1.28).

Each of the three tirzepatide doses reduced HbA1c more than the respective low, medium, and high dose of semaglutide. Doses of 10mg and 15mg were more efficacious in lowering body weight versus semaglutide 1.0mg or 2.0mg, and tirzepatide 2.5mg was more efficacious versus semaglutide 0.5mg or 1.0mg.

Compared to placebo, all doses of both drugs increased the risk of gastrointestinal adverse events, with tirzepatide yielding the highest relative risk (RR) for nausea (RR 3.57; 2.56 to 4.76), vomiting (4.35; 3.03 to 6.25), and diarrhoea (2.04; 1.56 to 2.63).

No difference was found between tirzepatide, semaglutide, and placebo regarding risk for serious adverse events. In patients with T2D, tirzepatide 5mg, 10mg, and 15mg were found to be more efficacious in reducing HbA1C compared to semaglutide 0.5mg, 1.0mg, and 2.0mg.

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Tirzepatide is evidently superior in efficacy to semaglutide and will likely cause Eli Lilly to become the market leader in the GLP-1 space, which will be further underscored by the eventual launch of the “triple G” agonist retatrutide. Furthermore, Novo Nordisk’s recent manufacturing and supply chain issues will lead to a serious challenge in its ability to meet demand for SC semaglutide and may lead to an erosion in its market share due to a combination of these issues and increased tirzepatide uptake.