A new meta-analysis combining 22 studies shows that tirzepatide is superior to semaglutide for both control of blood sugar and in terms of amount of body weight lost by patients. The study will be presented at the Annual Meeting of the European Association for the Study of Diabetes (EASD) in Hamburg, Germany (2–6 October), by Dr Thomas Karagiannis, Aristotle University of Thessaloniki, Thessaloniki, Greece, and colleagues.
There are few randomized controlled trials (RCTs) directly comparing subcutaneous tirzepatide with subcutaneous semaglutide. In this new research, the authors combined the data from 22 available trials to perform a meta-analysis to compare tirzepatide with semaglutide in terms of their efficacy and safety in people with type 2 diabetes.
The authors searched Medline and the Cochrane Library for RCTs that assessed a maintenance dose of subcutaneous tirzepatide 5, 10, or 15mg once-weekly or subcutaneous semaglutide 0.5, 1.0, or 2.0mg once-weekly for at least 12 weeks.
Comparators were any of the eligible doses of tirzepatide and semaglutide, placebo, and also other glucose-lowering drugs provided they were directly compared to tirzepatide and semaglutide in at least one trial. The meta-analysis then calculated any differences in effects on HbA1c (glycated haemoglobin, a measure of blood sugar control), body weight, and also the risk of adverse events.
The 22 RCTs included data from 18,472 patients, all with a diagnosis of type 2 diabetes. The authors found that tirzepatide 15mg was the most efficacious in reducing HbA1c versus placebo (mean difference -2.00%), followed by tirzepatide 10mg (-1.86%) and semaglutide 2.0mg (-1.62%).
Each of the three tirzepatide doses reduced HbA1c more than the respective low-, medium-, and high-dose of semaglutide. Versus placebo, tirzepatide was more efficacious in reducing body weight (-10.96Kg, -8.75Kg, and -6.16Kg for tirzepatide 15, 10, and 5mg respectively) than semaglutide (-5.24Kg, -4.44Kg, and -2.72Kg for semaglutide 2.0, 1.0, and 0.5mg respectively).
Regarding between-drug comparisons, both tirzepatide 10 and 15mg were more efficacious in lowering body weight versus semaglutide 0.5, 1.0, and 2.0mg, while tirzepatide 5mg was more efficacious versus semaglutide 0.5 and 1.0mg.
Although not in the journal abstract, the authors have been able to provide results for change in body weight from the analyses comparing tirzepatide and semaglutide (rather than versus placebo). These numerical values will be presented in the oral presentation in the congress.
The actual differences in change in body weight (mean difference) for the following comparisons are:
Tirzepatide 15mg versus semaglutide 2.0 mg = -5.72Kg (i.e., a mean of 5.72Kg more weight lost in those taking tirzepatide 15mg versus those taking semaglutide 2.0mg)
Tirzepatide 10mg versus semaglutide 2.0mg = -3.52 Kg
Tirzepatide 5mg versus semaglutide 1.0mg = -1.72 Kg
"In summary the three tirzepaide doses were more effective than the three respective semaglutide doses, with the difference between the two drugs being larger with the higher doses,” the authors noted.
As compared to placebo, all doses of tirzepatide and semaglutide increased risk for gastrointestinal adverse events, with tirzepatide 15mg yielding the highest increased risk (3.6 times) for nausea, vomiting (4.4 times) and diarrhoea (double the risk).
Between-drug comparisons yielded non-statistically significant results, except for tirzepatide 15mg versus semaglutide 1.0mg (39% increased vomiting risk) and 0.5mg (85% increased vomiting risk), and tirzepatide 15mg versus semaglutide 0.5mg (45% increased risk of nausea). There was no difference between tirzepatide, semaglutide and placebo regarding risk for serious adverse events.
"In people with type 2 diabetes, tirzepatide 5, 10, and 15mg were more efficacious in reducing HbA1c compared to semaglutide 0.5, 1.0, and 2.0mg, respectively,” the authors concluded. “Tirzepatide also was also more effective for weight loss than semaglutide, with a larger weight-loss effect at higher doses. High-dose tirzepatide (15mg) was associated with increased risk for vomiting versus low- and medium-dose semaglutide."