A meta-analysis of 22 randomised controlled trials – with data from nearly 19 000 patients – across Medline and the Cochrane Library, has suggested tirzepatide (Mounjaro; Eli Lilly) is superior to semaglutide for blood sugar control and weight loss.
The study was presented at the annual meeting of the European Association for the Study of Diabetes (EASD) in Hamburg, Germany this week.
The analysis included data from 18 742 patients with type 2 diabetes mellitus (T2DM) receiving 5.0mg, 10.0mg, or 15.0mg once-weekly subcutaneous tirzepatide or 0.5mg, 1.0mg, or 2.0mg once-weekly subcutaneous semaglutide for at least 12 weeks.
Comparisons were measured by calculating any differences in HbA1c, blood glucose control, body weight and risk of adverse events.
Authors found that tirzepatide 15mg was most effective in reducing HbA1c (mean difference, -2.0%), followed by tirzepatide 10mg (-1.9%) and semaglutide 2mg (-1.6%) compared with placebo.
They also found that each of the three tirzepatide doses reduced HbA1c more than the respective low, medium and high doses of semaglutide.
The results showed that tirzepatide was more effective in reducing body weight than semaglutide at all respective doses, reporting figures of -6.2kg, -8.8g, and -11.0kg and for tirzepatide 5.0mg, 10.0mg, and 15.0mg, respectively, versus -2.7kg, -4.4kg, and -5.2kg for semaglutide 0.5mg, 1.0mg, and 2.0mg, respectively.
Both tirzepatide and semaglutide were associated with increased risk of gastrointestinal adverse events compared with placebo at all doses, tirzepatide 15mg was associated with the highest risk for nausea (3.6 times), vomiting (4.4 times) and diarrhoea (2.0 times).
Commenting on the meta-analysis, Douglas Twenefour, head of care at Diabetes UK, said: “Tirzepatide will provide another effective treatment option for managing T2DM.
“It is very promising that the trial data showed great improvements in blood glucose management and weight loss,” he said.
Hannah Beba, consultant pharmacist in diabetes at West Yorkshire Health and Care Partnership, raised issues around the practicality of administration.
“Although Ozempic (semaglutide) is licensed to be used up to a dose of 2.0mg once weekly, in the UK, we do not use this dose as there is no pen device available that administers this,” she said.
“You would have to take two 1.0mg injections, which is not cost efficacious.”
In final draft guidance, published on 8 September 2023, the National Institute for Health and Care Excellence (NICE) recommended tirzepatide for the treatment of T2DM, reversing its initial decision against use of the drug in June 2023.
“Once [tirzepatide] is launched we will have discussions within our health systems about cost efficacy at the different doses for different cohorts of people living with T2DM,” said Beba.
“We will also reflect on the NICE criteria for access. If the 5.0mg [tirzepatide] is the same cost as 1.0mg Ozempic, then I would imagine [tirzepatide] 5.0mg would be used in preference to Ozempic.”
Beba highlighted that tirzepatide is still awaiting results from a cardiovascular outcome trial – ‘SURPASS-CVOT’, due late 2024 – which may influence recommendations.
“I certainly expect that tirzepatide will get an obesity licence. The SURMOUNT 1-4 trials have shown incredible results. It’s a new age of incretins,” she added.
Study details
Tirzepatide reduces albuminuria in patients with type 2 diabetes: post-hoc pooled analysis of SURPASS 1-5
RJ Wiese, H Heerspink, KR Tuttle, N. Sattar, et al.
Presented at the European Association for the Study of Diabetes Congress October 2023
Background and aims
There is paucity of randomised controlled trials (RCTs) directly comparing tirzepatide with subcutaneous (SC) semaglutide. We did a network meta-analysis to compare tirzepatide with SC semaglutide in terms of their efficacy and safety in people with type 2 diabetes.
Materials and methods
We searched Medline and the Cochrane Library for RCTs that assessed a maintenance dose of tirzepatide 5, 10, or 15 mg once-weekly or SC semaglutide 0.5, 1.0, or 2.0 mg 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. We did frequentist random-effects network meta-analyses and calculated mean differences (MDs) for change from baseline in HbA1c and body weight, and risk ratios (RRs) for incidence of gastrointestinal adverse events (nausea, vomiting, diarrhea) and serious adverse events.
Results
Twenty-two RCTs (18,472 participants) contributed data to the network meta-analysis. Tirzepatide 15 mg was the most efficacious in reducing HbA1c versus placebo (MD -2.00%; 95% CI -2.16 to -1.84), followed by tirzepatide 10 mg (-1.86%; -2.02 to -1.84) and semaglutide 2.0 mg (-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. Versus placebo, tirzepatide was more efficacious in reducing body weight. Regarding between-drug comparisons, both tirzepatide 10 and 15 mg were more efficacious in lowering body weight versus either semaglutide 1.0 or 2.0 mg, while tirzepatide 5 mg was more efficacious versus semaglutide 0.5 and 1.0 mg. As compared to placebo, all doses of tirzepatide and semaglutide increased risk for gastrointestinal adverse events, with tirzepatide 15 mg yielding the highest 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). Between-drug comparisons yielded non-significant results, except for tirzepatide 15 mg versus semaglutide 1.0 mg (1.39; 1.03 to 1.85) and 0.5 mg (1.85; 1.35 to 2.56) in vomiting, and versus semaglutide 0.5 mg (1.45; 1.09 to 1.92) in nausea. There was no difference between tirzepatide, semaglutide and placebo regarding risk for serious adverse events.
Conclusion
In people with type 2 diabetes, tirzepatide 5, 10, and 15 mg were more efficacious in reducing HbA1c compared to semaglutide 0.5, 1.0, and 2.0 mg, respectively. Superiority of tirzepatide over semaglutide was more pronounced in terms of body weight loss. High-dose tirzepatide (15 mg) was associated with increased protective effect
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