Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes
2021 · paper · Clinical trials
An open-label, 40-week trial comparing once-weekly tirzepatide with semaglutide in 1879 people with type 2 diabetes. Tirzepatide at all doses lowered glycated hemoglobin and body weight more than semaglutide; gastrointestinal events were the most common side effects.
1 finding
Wording The listed causes of death (6 Covid-related at 1/2/2/1, "Four other deaths" cardiovascular at 1/1/2/0, and "2 deaths ... indeterminate (1 each in the tirzepatide 5-mg and 10-mg groups)") add up to 12. The text and Table 2 report 13 deaths, 4 in each tirzepatide group. The 5-mg group accounts for only 3.
- p. 10 Results, deaths paragraph
Four other deaths were adju-dicated as cardiovascular-related deaths (1 in the tirzepatide 5-mg group
- p. 6 Table 2, Death row
4 (0.9)
- p. 10 Results, Other End Points and Safety, death paragraph
A total of 13 deaths (0.7%) occurred in the total population during the trial (4 patients in each of the three tirzepatide groups
- p. 10 Results, death breakdown
Four other deaths were adjudicated as cardiovascular-related deaths (1 in the tirzepatide 5-mg group, 1 in the tirzepatide 10-mg group, 2 in the tirzepatide 15-mg group
Only the authors can say what is right here.
Judge's note: Checked page 10 and the Table 2 death row on page 6 (4, 4, 4, 1; total 13). The 10-mg and 15-mg groups add up correctly; the 5-mg group is one short. The text does not name any other cause of death. Table S10, which is not in the files, may list it. The authors should account for the missing death.
Second check: another model agreed
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4 minor (typos and the like; most checked by the judge only)
Wording Limitations: "which allowed only 16 weeks at a steady state for the assessment of the highest tirzepatide dose". Under the stated escalation ("increased by 2.5 mg every 4 weeks"), 15 mg is reached at week 20, as the figure arrows show, which leaves 20 weeks of a 40-week trial.
- p. 12 Discussion, limitations paragraph
only 16 weeks at a steady state for the assess-
- p. 3 Methods, Procedures
2.5 mg every 4 weeks until the randomly assigned
- p. 8 Figure 1B/1D, maintenance-dose arrows
Arrows indicate the times at which the maintenance doses
- p. 12 Discussion, limitations paragraph
which allowed only 16 weeks at a steady state for the assess-ment of the highest tirzepatide dose
Only the authors can say what is right here.
Judge's note: Page 3 gives the escalation from 2.5 mg in 2.5-mg steps every 4 weeks, so 15 mg is reached at week 20. The arrows in Fig. 1B/1D (page 8) and Fig. 2B (page 9) sit at week 20 for 15 mg. Sixteen weeks would hold only if "steady state" means pharmacokinetic steady state about 4 weeks after the last increase (the paper gives a half-life of about 5 days). The paper never defines that lag, so the authors should clarify.
Second check: another model agreed
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Wording Results: "Two patients with cardiovascular-related deaths had no previous cardiovascular risk factors other than type 2 diabetes". Discussion: of five cardiovascular deaths, "three of those patients had previous risk factors and established cardiovascular disease, and a fourth was a smoker and was overweight", which leaves only one patient without risk factors.
- p. 10 Results, deaths paragraph
Two patients with cardiovascular-related deaths had no previous cardiovascular risk factors other than type 2 diabetes.
- p. 12 Discussion, first paragraph
three of those pa-tients had previous risk factors and established cardiovascular disease, and a fourth was a smok-er and was overweight.
- p. 11 Discussion
Five deaths were adjudicated to be related to cardio-vascular causes
- p. 11 Discussion, paragraph 3
Five deaths were adjudicated to be related to cardio-vascular causes, all in the tirzepatide groups
Only the authors can say what is right here.
Judge's note: Checked pages 10, 11 and 12. The total of five cardiovascular deaths agrees in both places (4 other cardiovascular deaths plus the presumptive Covid death). The counts reconcile only if smoking and overweight are not treated as "previous cardiovascular risk factors", and smoking is a standard cardiovascular risk factor. The descriptions are at least ambiguous; the authors should say whether one or two patients had no risk factors other than diabetes.
Second check: another model agreed
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Typo "The glycated hemoglobin level over time is shown in (Fig. 1B)." The parentheses after "shown in" are redundant; it should read "shown in Fig. 1B".
- p. 4 Results, Glycemic End Points
cated hemoglobin level over time is shown in (Fig. 1B).
- p. 4 Results, Glycemic End Points
The glycated hemoglobin level over time is shown in (Fig. 1B).
Judge's note: Seen on page 4, right column. A cosmetic copy-editing slip.
Second check: none (judge only)
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Typo "changes in aspartate aminotransferase ranged from and −9 to −14%" has a stray "and"; it should read "ranged from −9 to −14%".
- p. 10 Results, Other End Points and Safety
aminotransferase ranged from and −9 to −14%
- p. 10 Other End Points and Safety, liver enzymes
changes in aspartate aminotransferase ranged from and −9 to −14%
- p. 10 Other End Points and Safety
ranged from and −9 to −14%
Judge's note: The page 10 image shows the stray word, so this is not an extraction artefact.
Second check: none (judge only)