Table 5 Summary of count data analysis with random effects or fixed effects ORs (95% CI) estimate with a p-value for analysis of primary safety outcomes based on various type of comparators

All adverse events (AEs)

GLP-1 RA

1.05 (0.99, 1.11)

P ≥ 0.05

1.11 (1.05, 1.17)

P < 0.05

1.12 (1.06, 1.18)

P < 0.05

Insulin

1.203 (0.97, 1.09)

P ≥ 0.05

1.06 (1.01, 1.12)

P < 0.05

1.12 (1.06, 1.18)

P < 0.05

Placebo

1.10 (0.94, 1.30)

P ≥ 0.05

1.00 (0.92, 1.10)

P ≥ 0.05

1.04 (0.95, 1.13)

P ≥ 0.05

overall

1.04 (1.00, 1.09)

P ≥ 0.05

1.07 (1.03, 1.11)

P < 0.05

1.10 (1.07, 1.14)

P < 0.05

Serious adverse event

GLP-1 RA

1.54 (1.08, 2.19)

P < 0.05

1.30 (0.90, 1.88)

P ≥ 0.05

1.32 (0.91, 1.89)

P ≥ 0.05

Insulin

0.99 (0.93, 1.05)

P ≥ 0.05

1.00 (0.94, 1.06)

P ≥ 0.05

0.96 (0.91, 1.02)

P ≥ 0.05

Placebo

1.86 (0.47, 7.31)

P ≥ 0.05

1.01 (0.98, 1.04)

P ≥ 0.05

0.98 (0.95, 1.01)

P ≥ 0.05

overall

1.04 (0.97, 1.10)

P ≥ 0.05

1.02 (0.98, 1.05)

P ≥ 0.05

0.99 (0.95, 1.02)

P ≥ 0.05

Hypoglycemic events

GLP-1 RA

1.39 (0.45, 4.31)

P ≥ 0.05

1.85 (0.63, 5.42)

P ≥ 0.05

1.39 (0.45, 4.31)

P ≥ 0.05

Insulin

0.72 (0.67, 0.78)

P < 0.05

0.78 (0.072, 0.84)

P < 0.05

0.72 (0.67, 0.78)

P < 0.05

Placebo

8.37 (1.07, 65.51)

P < 0.05

1.16 (1.11, 1.22)

P < 0.05

8.37 (1.07, 65.51)

P < 0.05

overall

0.75 (0.69, 0.81)

P < 0.05

0.93 (0.89, 0.98)

P < 0.05

0.75 (0.69, 0.81)

P < 0.05

Gastrointestinal events

GLP-1 RA

1.062 (0.951, 1.186)

P ≥ 0.05

1.231 (1.110, 1.366)

P < 0.05

1.260 (1.140, 1.392)

P < 0.05

Insulin

–

–

–

Placebo

2.802 (0.296, 26.544)

P ≥ 0.05

5.603 (0.685, 45.822)

P ≥ 0.05

7.533 (0.957, 59.279)

P ≥ 0.05

overall

1.078 (0.965, 1.203)

P ≥ 0.05

1.262 (1.138, 1.400) P < 0.05

1.296 (1.172, 1.432)

P < 0.05

Discontinuation of therapy

GLP-1 RA

1.34 (0.94, 1.91)

P ≥ 0.05

1.92 (1.38, 2.67)

P < 0.05

1.95 (1.41, 2.71)

P < 0.05

Insulin

1.19 (0.11, 1.28)

P ≥ 0.05

1.12 (1.03, 1.22)

P < 0.05

1.19 (1.10, 1.29)

P < 0.05

Placebo

1.55 (0.38, 6.38)

P ≥ 0.05

1.01 (0.98, 1.05)

P ≥ 0.05

0.98 (0.94, 1.03)

P ≥ 0.05

overall

1.22 (1.12, 1.33)

P < 0.05

1.13 (1.07, 1.19)

P < 0.05

1.15 (1.09, 1.21)

P < 0.05

Fatal adverse events

GLP-1 RA

Insulin

1.03 (0.98, 1.08)

P ≥ 0.05

0.95 (0.91, 1.00)

P ≥ 0.05

0.98 (0.93, 1.03)

P ≥ 0.05

Placebo

0.98 (0.96, 1.00)

P ≥ 0.05

1.00 (0.99,1.00)

P ≥ 0.05

overall

1.04 (0.98, 1.09)

P ≥ 0.05

0.98 (0.96, 1.00)

P ≥ 0.05

1.00 (0.97, 1.02)

P ≥ 0.05

Decreased appetite

GLP-1 RA

1.62 (1.20, 2.19)

P < 0.05

1.62 (1.20, 2.19)

P < 0.05

1.64 (1.31, 2.06

P < 0.05

Insulin

1.02 (0.94, 1.10)

P ≥ 0.05

1.05 (0.96, 1.15)

P ≥ 0.05

1.09 (1.00, 1.19)

P ≥ 0.05

Placebo

12.68 (1.63, 98.56)

P < 0.05

0.99 (0.94, 1.03)

P ≥ 0.05

1.00 (0.96, 1.05)

P ≥ 0.05

overall

1.17 (1.07, 1.29)

P < 0.05

1.07 (1.02, 1.13)

P < 0.05

1.12 (1.06, 1.19)

P < 0.05