Table 2 Summary of the body weight reduction across the PIONEER trials considering the trial product without rescue medication (trial product estimand)

PIONEER 1

Sema 3 mg

− 1.7

− 0.2 (− 1.0 to 0.6)

0.71

–

–

–

Sema 7 mg

− 2.5

− 1.0 (− 1.8 to − 0.2)

0.01

–

–

–

Sema 14 mg

− 4.1

− 2.6 (− 3.4 to − 1.8)

< 0.001

–

–

–

Pbo

− 1.5

–

–

–

–

–

PIONEER 2

Sema 14 mg

− 4.2

− 0.4 (− 1.0 to 1.0)

0.1358

− 4.7

− 0.9 (− 1.6 to − 0.2)

0.0114

Empa 25 mg

− 3.8

–

–

− 3.8

–

–

PIONEER 3

Sema 3 mg

− 1.3

− 0.5 (− 1.0 to − 0.1)

0.03

− 1.7

− 0.7 (− 1.3 to − 0.1)

0.02

Sema 7 mg

− 2.4

− 1.5 (− 2.0 to − 1.1)

< 0.001

− 2.5

− 1.5 (− 2.1 to − 0.9)

< 0.001

Sema 14 mg

− 3.6

− 2.6 (− 3.1 to − 2.1)

< 0.001

− 4.2

− 2.9 (− 3.5 to − 2.3)

< 0.001

Sita 100 mg

− 0.7

–

–

− 0.9

–

–

PIONEER 4

Sema 14 mg

− 4.7

− 1.5 (− 2.2 to − 0.9)^a

< 0.0001^a

− 5.0

− 1.8 (− 2.6 to − 1.0)^a

< 0.0001^a

− 4.0 (− 4.8 to − 3.2)^b

< 0.0001^b

− 3.8 (− 4.8 to − 2.7)^b

< 0.0001^b

Lira 1.8 mg

− 3.2

–

–

− 3.1

–

–

Pbo

− 0.7

–

–

− 1.2

–

–

PIONEER 5

Sema 14 mg

− 3.7

− 2.7 (− 3.5 to − 1.9)

< 0.0001

–

–

–

Pbo

− 1.1

–

–

–

–

–

PIONEER 7

Sema flex

–

–

–

− 2.9 (SE 0.3)

− 2.2 (− 2.9 to − 1.5)

< 0.0001

Sita 100 mg

–

–

–

− 0.8 (SE 0.3)

–

–

PIONEER 8

Sema 3 mg

− 1.3

− 0.9 (− 1.6 to − 0.2)

0.0111

− 1.0

− 1.6 (− 2.6 to − 0.7)

0.0009

Sema 7 mg

− 3.0

− 2.5 (− 3.2 to − 1.8)

< 0.0001

− 2.9

− 3.5 (− 4.5 to − 2.6)

< 0.0001

Sema 14 mg

− 4.1

− 3.7 (− 4.4 to − 3.0)

< 0.0001

− 4.3

− 4.9 (− 5.9 to − 3.9)

< 0.0001

Pbo

− 0.4

–

–

0.6

–

–