Liraglutide antidiabetic drugs

Description Results NMA

CV events 1.00 [0.06; 15.89]

liraglutide (n=-9)

vs.

placebo (n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

liraglutide 0.6 mg/day (n=88)

vs.

placebo (n=88)

3 arms:liraglutide 0.6 mg/day, 0.9 mg/day or placebo

double-blind

Parallel groups

Sample size: 88/88

Primary endpoint:

FU duration: 24 weeks

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

CV events 0.88 [0.79; 0.97] Demonstrated

all causes death 0.85 [0.75; 0.97]

CVdeath 0.79 [0.66; 0.94]

Microvascular event 0.85 [0.75; 0.98]

Nephropathy 0.80 [0.68; 0.93]

fatal and non fatal stroke 0.87 [0.71; 1.06]

fatal and non fatal MI 0.86 [0.74; 1.00]

Hospitalization for heart failure 0.88 [0.74; 1.05]

Retinopathy 1.15 [0.87; 1.52]

Maximum dose of 1.8 mg liraglutide, injected subcutaneously once daily (n=4668)

vs.

placebo (n=4672)

double-blind

Sample size: 4668/4672

Primary endpoint: cardiovascular death, non-fatal myocardial infarction, non-fatal stroke

FU duration: 3.8 years (median)

death NaN [NaN; NaN]

CV events NaN [NaN; NaN]

severe hypoglycemia NaN [NaN; NaN]

ant hypoglycemia NaN [NaN; NaN]

death NaN [NaN; NaN]

CV events NaN [NaN; NaN]

vomiting ∞ [NaN; ∞]

diarrhoea ∞ [NaN; ∞]

severe hypoglycemia NaN [NaN; NaN]

ant hypoglycemia ∞ [NaN; ∞]

CV events NaN [NaN; NaN]

nausea 2.93 [0.38; 22.40]

vomiting ∞ [NaN; ∞]

diarrhoea 1.69 [0.70; 4.11]

Liraglutide 0.1, 0.3, 0.6 or 0.9 mg once daily for 14 weeks (n=180)

vs.

Placebo (n=46)

randomized after OAD discontinuation and washout

double blind

Parallel groups

Sample size: 180/46

Primary endpoint: HbA1c

FU duration: 14 weeks

phase 2

Liraglutide 0.045, 0.225, 0.45, 0.60, and 0.75 mg daily (n=135)

vs.

Placebo (n=29)

open

Sample size: 135/29

Primary endpoint: change in HbA1c

FU duration: 12 weeks

dose-response study

single daily subcutaneous dose of 0.6 mg liraglutide for 8 weeks (n=21)

vs.

placebo (n=12)

double-blind

Parallel groups

Sample size: 21/12

Primary endpoint: not defined

FU duration: 8 weeks

liraglutide 0.65 mg, 1.25 mg or 1.9 mg for 14 weeks (n=123)

vs.

placebo (n=40)

double-blind

Parallel groups

Sample size: 123/40

Primary endpoint: not unique

FU duration: 14 weeks

phase 2, dose ranging

vomiting 22.27 [3.11; 159.74]

death NaN [NaN; NaN]

severe hypoglycemia NaN [NaN; NaN]

nausea 4.30 [1.06; 17.42]

severe hypoglycemia ∞ [NaN; ∞]

CV events 1.24 [0.34; 4.55]

severe hypoglycemia NaN [NaN; NaN]

nausea 3.97 [1.44; 10.94]

diarrhoea 3.80 [1.17; 12.39]

CV events 2.48 [0.29; 20.97]

vomiting 1.86 [0.63; 5.47]

death NaN [NaN; NaN]

severe hypoglycemia NaN [NaN; NaN]

nausea 10.76 [3.34; 34.64]

vomiting 15.13 [2.02; 113.61]

diarrhoea 7.73 [2.35; 25.40]

CV events 0.75 [0.17; 3.28]

Liraglutide 1.2 mg daily (n=241)

vs.

Placebo on-top of Metformin (n=122)

5 arms : liraglutide 0.6, 1.2 or 1.8 mg, glimeripide 4mg once daily or placebo

double blind

Parallel groups

Sample size: 241/122

Primary endpoint: change in A1C

FU duration: 26 weeks

Liraglutide 1.2 mg daily (n=228)

vs.

Placebo on-top of sulphonylureas (n=115)

5 arms liraglutide 0.6, 1.2 or 1.8mg, rosiglitazone or placebo

double-blind

Parallel groups

Sample size: 228/115

Primary endpoint: change in HbA1c

FU duration: 26 weeks

Liraglutide 1.2 daily (n=178)

vs.

Placebo on-top of thiazolidinediones + metformin (n=177)

3 arms: liraglutide 1.2 or 1.8 mg, placebo

double-blind

Parallel groups

Sample size: 178/177

Primary endpoint: change in A1C

FU duration: 26 weeks

Liraglutide 1.8 mg daily (n=232)

vs.

Placebo on-top of sulphonylureas+metformin (n=115)

double-blind

Parallel groups

Sample size: 232/115

Primary endpoint: change in HbA1c

FU duration: 26 weeks

Liraglutide 1.2mg daily for 26 weeks (n=241)

vs.

Glimepiride on-top of Metformin (n=244)

5 arms: Liraglutide 0.6, 1.2 or 1.8 mg daily, glimepiride 4mg od, placebo

double blind

Parallel groups

Sample size: 241/244

Primary endpoint: change in A1C

FU duration: 26 weeks

Liraglutide 1.8 mg daily (n=232)

vs.

Glargine on-top of sulphonylureas+metformin (n=234)

open

Parallel groups

Sample size: 232/234

Primary endpoint: change in HbA1c

FU duration: 26 weeks

liraglutide added to metformin (n=-9)

vs.

glimepiride added to metformin (n=-9)

Sample size: -9/-9

Primary endpoint: Change in Glycosylated Haemoglobin A1c

FU duration:

Liraglutide 1.8 daily (n=178)

vs.

Placebo on-top of thiazolidinediones + metformin (n=177)

3 arms: liraglutide 1.2 or 1.8 mg, placebo

double-blind

Sample size: 178/177

Primary endpoint: change in A1C

FU duration: 26 weeks

Liraglutide 1.8 mg daily (n=234)

vs.

Placebo on-top of sulphonylureas (n=114)

5 arms liraglutide 0.6, 1.2 or 1.8mg, rosiglitazone or placebo

double-blind

Parallel groups

Sample size: 234/114

Primary endpoint: change in HbA1c

FU duration: 26 weeks

Liraglutide 0.6, 1.2 or 1.8 mg daily (n=228)

vs.

rosiglitazone on-top of sulphonylureas (n=232)

5 arms liraglutide 0.6, 1.2 or 1.8mg, rosiglitazone or placebo

double-blind

Parallel groups

Sample size: 228/232

Primary endpoint: change in HbA1c

FU duration: 26 weeks

Liraglutide 1.8 mg daily for 26 weeks (n=242)

vs.

Glimepiride on-top of Metformin (n=244)

5 arms: Liraglutide 0.6, 1.2 or 1.8 mg daily,glimepiride or placebo

double blind

Parallel groups

Sample size: 242/244

Primary endpoint: change in A1C

FU duration: 26 weeks

Liraglutide 1.8 mg daily (n=242)

vs.

Placebo on-top of Metformin (n=122)

5 arms : liraglutide 0.6, 1.2 or 1.8 mg, glimeripide 4mg once daily or placebo

double blind

Parallel groups

Sample size: 242/122

Primary endpoint: change in A1C

FU duration: 26 weeks

liraglutide 0.9 mg/day (n=88)

vs.

placebo (n=88)

3 arms:liraglutide 0.6 mg/day, 0.9 mg/day or placebo

double-blind

Sample size: 88/88

Primary endpoint:

FU duration: 24 weeks

ant hypoglycemia 0.05 [0.01; 0.41]

death NaN [NaN; NaN]

CV events NaN [NaN; NaN]

vomiting 0.58 [0.06; 5.34]

diarrhoea ∞ [NaN; ∞]

severe hypoglycemia NaN [NaN; NaN]

death NaN [NaN; NaN]

CV events NaN [NaN; NaN]

nausea 0.68 [0.15; 3.12]

vomiting 0.77 [0.09; 6.70]

severe hypoglycemia NaN [NaN; NaN]

ant hypoglycemia 0.48 [0.10; 2.39]

nausea 3.25 [2.06; 5.12]

vomiting 3.40 [1.65; 7.00]

diarrhoea 1.75 [1.07; 2.87]

death 0.00 [0.00; NaN]

severe hypoglycemia NaN [NaN; NaN]

serious adverse events 1.22 [0.60; 2.47]

nausea 4.56 [2.36; 8.80]

death 0.00 [0.00; NaN]

CV events 0.97 [0.06; 15.46]

vomiting 1.87 [0.85; 4.11]

diarrhoea 1.59 [0.74; 3.42]

serious adverse events 1.49 [0.43; 5.19]

severe adverse events 0.87 [0.32; 2.35]

severe adverse events 2.80 [1.12; 6.97]

nausea 0.91 [0.67; 1.23]

vomiting 0.60 [0.32; 1.14]

diarrhoea 1.02 [0.63; 1.66]

severe hypoglycemia 0.00 [0.00; NaN]

serious adverse events 1.97 [0.75; 5.17]

death ∞ [NaN; ∞]

diarrhoea 1.67 [0.63; 4.44]

severe hypoglycemia NaN [NaN; NaN]

treatment-emergent adverse events (TEAEs) 0.99 [0.87; 1.12]

serious adverse events 0.80 [0.34; 1.88]

severe adverse events 1.48 [0.30; 7.22]

nausea 5.93 [3.11; 11.28]

vomiting 2.34 [1.10; 5.00]

diarrhoea 2.51 [1.24; 5.10]

death 1.00 [0.06; 15.96]

CV events 0.97 [0.06; 15.46]

serious adverse events 1.51 [0.43; 5.27]

severe adverse events 0.88 [0.32; 2.38]

nausea 3.84 [2.63; 5.59]

vomiting 2.57 [1.21; 5.43]

diarrhoea 2.10 [1.30; 3.38]

severe hypoglycemia NaN [NaN; NaN]

serious adverse events 0.62 [0.26; 1.46]

Liraglutide 0.045, 0.225, 0.45, 0.60, and 0.75 mg daily (n=135)

vs.

Glimepiride (n=26)

open

Parallel groups

Sample size: 135/26

Primary endpoint: change in HbA1c

FU duration: 12 weeks

dose-response study

Liraglutide 0.045, 0.225, 0.45, 0.6 or 0.75 mg daily for 12 weeks (n=176)

vs.

metformin 1000mg twice daily (n=34)

double blind (not adequate)

Parallel groups

Sample size: 176/34

Primary endpoint: not defiend

FU duration: 12 weeks

phase 2 dose response study

liraglutide 1.2 mg daily (n=251)

vs.

glimepiride 8 mg once daily (n=248)

3 arms : liraglutide 1.2 or 1.8 mg daily or glimepiride 8 mg once daily

double blind

Parallel groups

Sample size: 251/248

Primary endpoint: Change in Glycosylated Haemoglobin A1c (HbA1c) , ,

FU duration: 52 weeks (104 weeks)

phase 3

liraglutide 1.2mg subcutaneously once daily (n=225)

vs.

oral sitagliptin 100mg once daily (n=219)

2 dose of liraglutide 1.2 and 1.8 mg

open

Parallel groups

Sample size: 225/219

Primary endpoint: change in HbA1c

FU duration: 26 weeks

liraglutide 1.8 mg once a day (n=233)

vs.

exenatide 10 microg twice a day (n=231)

open

Parallel groups

Sample size: 233/231

Primary endpoint: change in glycosylated haemoglobin

FU duration: 26 weeks

liraglutide 0.9 mg once daily (n=272)

vs.

glibenclamide once or twice daily at a planned maximum dose of 2.5 mg/day, before or after meals (n=139)

double-blind

Parallel groups

Sample size: 272/139

Primary endpoint: HbA1c

FU duration: 24-week

liraglutide 1.8mg subcutaneously once daily (n=221)

vs.

oral sitagliptin 100mg once daily (n=219)

2 dose of liraglutide 1.2 and 1.8 mg

open

Parallel groups

Sample size: 221/219

Primary endpoint: change in HbA1c

FU duration: 26 weeks

liraglutide 1.8 mg daily (n=247)

vs.

glimepiride 8 mg once daily (n=248)

3 arms : liraglutide 1.2 or 1.8 mg daily or glimepiride 8 mg once daily

double blind

Parallel groups

Sample size: 247/248

Primary endpoint: Change in Glycosylated Haemoglobin A1c (HbA1c) , ,

FU duration: 52 weeks (104 weeks)

phase 3

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

4 liraglutide doses (1.2 mg, 1.8 mg, 2.4 mg, or 3.0 mg daily) (n=-9)

vs.

placebo (n=-9)

3rd arms with orlistat 120 mg three times a day orally (n = 95)

double blind

Parallel groups

Sample size: -9/-9

Primary endpoint:

FU duration: 20 weeks