Body weight change in kilograms (diabetes)
Type 2 diabetes (adults); background therapy: one or more non insulin glucose lowering drugs
In plain language
Across 18 trials with 10,200 participants, 7 of 10 treatments had a clearly better result than placebo on body weight change in kilograms (diabetes), and for 3 the evidence could not tell them apart from placebo. The most favorable estimate was for Tirzepatide injection: mean difference -5.13 kg (95% credible interval -7.19 to -3.14).
Lower values favor the treatment. "Clearly" means the 95% credible interval excludes no difference. These are averages across trials; they do not say how any one person will respond. Not medical advice.
Network of trials
Effects compared with Placebo
| Treatment | Bayesian MD (95% CrI) | 95% prediction interval | Frequentist MD (95% CI) | Verdict |
|---|---|---|---|---|
| Tirzepatide injection TIRZ_SC | -5.13 (-7.19 to -3.14) | -7.72 to -2.57 | -5.16 (-7.06 to -3.26) | Better |
| Semaglutide injection SEMA_SC | -3.85 (-5.19 to -2.49) | -5.94 to -1.71 | -3.84 (-5.02 to -2.67) | Better |
| Semaglutide tablet SEMA_PO | -2.91 (-4.02 to -1.87) | -4.88 to -0.99 | -2.91 (-3.85 to -1.98) | Better |
| Liraglutide injection LIRA_SC | -2.09 (-3.22 to -0.99) | -4.02 to -0.14 | -2.09 (-3.06 to -1.12) | Better |
| Exenatide injection EXEN_SC | -2.04 (-3.65 to -0.50) | -4.32 to 0.16 | -2.06 (-3.43 to -0.69) | Better |
| Lixisenatide injection LIXI_SC | -1.39 (-2.66 to -0.17) | -3.44 to 0.65 | -1.40 (-2.45 to -0.34) | Better |
| Dulaglutide injection DULA_SC | -1.19 (-2.03 to -0.41) | -3.04 to 0.58 | -1.19 (-1.90 to -0.47) | Better |
| Sitagliptin SITAGLIPTIN | -0.68 (-1.82 to 0.42) | -2.64 to 1.29 | -0.67 (-1.63 to 0.29) | Unclear |
| Insulin glargine with lixisenatide injection IGLARLIXI_SC | 0.13 (-1.48 to 1.66) | -2.11 to 2.32 | 0.12 (-1.24 to 1.47) | Unclear |
| Insulin glargine INS_GLARGINE | 1.07 (-0.24 to 2.33) | -0.98 to 3.11 | 1.06 (-0.05 to 2.17) | Unclear |
Ranking
League table
| Row versus column | PLACEBO | TIRZ_SC | SEMA_SC | SEMA_PO | LIRA_SC | EXEN_SC | LIXI_SC | DULA_SC | SITAGLIPTIN | IGLARLIXI_SC | INS_GLARGINE |
|---|---|---|---|---|---|---|---|---|---|---|---|
| PLACEBO | PLACEBO | 5.13 3.14 to 7.19 | 3.85 2.49 to 5.19 | 2.91 1.87 to 4.02 | 2.09 0.99 to 3.22 | 2.04 0.50 to 3.65 | 1.39 0.17 to 2.66 | 1.19 0.41 to 2.03 | 0.68 -0.42 to 1.82 | -0.13 -1.66 to 1.48 | -1.07 -2.33 to 0.24 |
| TIRZ_SC | -5.13 -7.19 to -3.14 | TIRZ_SC | -1.30 -3.68 to 1.06 | -2.21 -4.46 to -0.01 | -3.04 -5.28 to -0.84 | -3.07 -5.54 to -0.65 | -3.73 -6.10 to -1.44 | -3.94 -5.98 to -1.94 | -4.45 -6.73 to -2.24 | -5.26 -7.69 to -2.74 | -6.19 -8.51 to -3.96 |
| SEMA_SC | -3.85 -5.19 to -2.49 | 1.30 -1.06 to 3.68 | SEMA_SC | -0.94 -2.36 to 0.53 | -1.76 -3.33 to -0.17 | -1.80 -3.77 to 0.24 | -2.46 -4.09 to -0.76 | -2.65 -4.10 to -1.15 | -3.17 -4.50 to -1.90 | -3.98 -5.89 to -1.94 | -4.91 -6.62 to -3.18 |
| SEMA_PO | -2.91 -4.02 to -1.87 | 2.21 0.01 to 4.46 | 0.94 -0.53 to 2.36 | SEMA_PO | -0.82 -1.98 to 0.32 | -0.87 -2.62 to 0.92 | -1.53 -2.90 to -0.13 | -1.72 -2.81 to -0.64 | -2.23 -3.19 to -1.29 | -3.05 -4.68 to -1.31 | -3.98 -5.46 to -2.53 |
| LIRA_SC | -2.09 -3.22 to -0.99 | 3.04 0.84 to 5.28 | 1.76 0.17 to 3.33 | 0.82 -0.32 to 1.98 | LIRA_SC | -0.05 -1.82 to 1.77 | -0.70 -2.18 to 0.78 | -0.89 -2.01 to 0.25 | -1.42 -2.58 to -0.24 | -2.22 -3.89 to -0.40 | -3.15 -4.63 to -1.63 |
| EXEN_SC | -2.04 -3.65 to -0.50 | 3.07 0.65 to 5.54 | 1.80 -0.24 to 3.77 | 0.87 -0.92 to 2.62 | 0.05 -1.77 to 1.82 | EXEN_SC | -0.67 -2.58 to 1.26 | -0.86 -2.37 to 0.68 | -1.37 -3.24 to 0.43 | -2.18 -4.29 to -0.03 | -3.11 -4.92 to -1.23 |
| LIXI_SC | -1.39 -2.66 to -0.17 | 3.73 1.44 to 6.10 | 2.46 0.76 to 4.09 | 1.53 0.13 to 2.90 | 0.70 -0.78 to 2.18 | 0.67 -1.26 to 2.58 | LIXI_SC | -0.20 -1.49 to 1.13 | -0.71 -2.04 to 0.56 | -1.51 -2.87 to -0.08 | -2.45 -3.91 to -0.96 |
| DULA_SC | -1.19 -2.03 to -0.41 | 3.94 1.94 to 5.98 | 2.65 1.15 to 4.10 | 1.72 0.64 to 2.81 | 0.89 -0.25 to 2.01 | 0.86 -0.68 to 2.37 | 0.20 -1.13 to 1.49 | DULA_SC | -0.52 -1.69 to 0.66 | -1.32 -2.80 to 0.20 | -2.26 -3.34 to -1.19 |
| SITAGLIPTIN | -0.68 -1.82 to 0.42 | 4.45 2.24 to 6.73 | 3.17 1.90 to 4.50 | 2.23 1.29 to 3.19 | 1.42 0.24 to 2.58 | 1.37 -0.43 to 3.24 | 0.71 -0.56 to 2.04 | 0.52 -0.66 to 1.69 | SITAGLIPTIN | -0.81 -2.38 to 0.86 | -1.74 -3.21 to -0.29 |
| IGLARLIXI_SC | 0.13 -1.48 to 1.66 | 5.26 2.74 to 7.69 | 3.98 1.94 to 5.89 | 3.05 1.31 to 4.68 | 2.22 0.40 to 3.89 | 2.18 0.03 to 4.29 | 1.51 0.08 to 2.87 | 1.32 -0.20 to 2.80 | 0.81 -0.86 to 2.38 | IGLARLIXI_SC | -0.93 -2.37 to 0.46 |
| INS_GLARGINE | 1.07 -0.24 to 2.33 | 6.19 3.96 to 8.51 | 4.91 3.18 to 6.62 | 3.98 2.53 to 5.46 | 3.15 1.63 to 4.63 | 3.11 1.23 to 4.92 | 2.45 0.96 to 3.91 | 2.26 1.19 to 3.34 | 1.74 0.29 to 3.21 | 0.93 -0.46 to 2.37 | INS_GLARGINE |
Heterogeneity, fit and convergence
Bayesian random effects (primary)
Frequentist check (netmeta)
Inconsistency
No comparison here has both direct and indirect evidence, so inconsistency cannot be checked by node splitting; the between designs Q above is the global check.
Small study effects
Fewer than ten trial comparisons, too few to judge funnel plot asymmetry.
Baseline characteristics of the trials
| Trial | Baseline BMI or body weight (kg/m2) effect modifier, prognostic factor; 17 of 18 | Sex (percent female) effect modifier, prognostic factor; 18 of 18 | Background glucose lowering therapy (stratum S0 to S4) effect modifier, prognostic factor; 18 of 18 | Asian ancestry or region (percent Asian) effect modifier, prognostic factor; 16 of 18 | Kidney function (eGFR) (mL/min/1.73 m2) prognostic factor, effect modifier; 6 of 18 | Treatment duration (weeks) effect modifier; 18 of 18 | Lifestyle co-intervention intensity (none standard intensive) effect modifier, prognostic factor; 18 of 18 |
|---|---|---|---|---|---|---|---|
| NCT03131687 S000010 | 32.57 | 46.85 | S1 | 1.66 | 93.19 | 26 | standard |
| PIONEER 4 S000133 | 32.94 | 48 | S1 | 13.4 | 95.8 | 52 | not_reported |
| NCT01476475 S000191 | 32.1 | 48.92 | S1 | 0.62 | not reported | 24 | not_reported |
| PIONEER 10 S000234 | 26.26 | 25.74 | S1 | 100 | 96.57 | 52 | not_reported |
| NCT01584232 S000246 | 26 | 28.51 | S1 | 100 | not reported | 26 | not_reported |
| AWARD-10 S000305 | 32.68 | 49.99 | S1 | not reported | not reported | 24 | not_reported |
| NCT00976937 S000415 | 36.8 | 59.9 100 minus male share | S1 | 0.6 | not reported | 24 | not_reported |
| SUSTAIN 9 S000483 | 31.9 | 41.72 | S1 | 23.51 | 95.2 | 30 | not_reported |
| PIONEER 12 S000522 | 28.58 | 41.7 | S1 | 75.22 | 103.5 | 26 | not_reported |
| AWARD-8 S001068 | 31.2 | 55.86 | S1 | 1.7 | not reported | 24 | not_reported |
| LIRA-SWITCH™ S001119 | 31.95 | 40.5 | S1 | not reported | not reported | 26 | not_reported |
| AWARD-2 S001130 | 31.55 | 48.52 | S1 | 16.91 | not reported | 78 | not_reported |
| AWARD-6 S001184 | 33.56 | 52.09 | S1 | 0.17 | not reported | 26 | not_reported |
| SUSTAIN S001311 | 27.8 | 42.5 | S1 | 85.03 | 109.33 median | 30 | not_reported |
| LIXILAN JP-O1 S002018 | 26.82 | 35.85 | S1 | 100 region: all sites in Asia | not reported | 52 | not_reported |
| AWARD-1 S002153 | 33.16 | 41.51 | S1 | 2.45 | eGFR below 60: 2.8 percent | 52 | not_reported |
| GETGOAL-M S002188 | 32.85 | 58.44 | S1 | 8.2 | not reported | 24 | not_reported |
| PIONEER 3 S002267 | not reported | 47.16 | S1 | 13.14 | not reported | 78 | not_reported |
Comparability of the trials
- FlagBaseline, Baseline BMI or body weight: design means range from 26.3 (DULA_SC vs SEMA_PO) to 36.8 (LIXI_SC vs SITAGLIPTIN) kg/m2; threshold 3
- FlagBaseline, Sex: design means range from 25.7 (DULA_SC vs SEMA_PO) to 59.9 (LIXI_SC vs SITAGLIPTIN) percent female; threshold 15
- FlagBaseline, Asian ancestry or region: design means range from 0.2 (DULA_SC vs LIRA_SC) to 100.0 (DULA_SC vs SEMA_PO) percent Asian; threshold 30
- FlagBaseline, Kidney function (eGFR): not reported by 12 of 18 trials
- FlagBaseline, Kidney function (eGFR): design means range from 93.2 (DULA_SC vs PLACEBO vs TIRZ_SC) to 109.3 (SEMA_SC vs SITAGLIPTIN) mL/min/1.73 m2; threshold 15
- FlagBaseline, Treatment duration: design means range from 24.0 (DULA_SC vs PLACEBO) to 52.0 (DULA_SC vs EXEN_SC vs PLACEBO) weeks; threshold 26
- NoteOutcome assessment, time point: selected time points span 24 to 30 weeks
- NoteOutcome assessment, analysis set: mixed: full_analysis 8, modified_itt 10
- NoteOutcome assessment, definition: mixed: change in HbA1c from baseline 1, change in HbA1c from baseline to week 26, LOCF 1, not stated 16
- NoteOutcome assessment, intercurrent events (discontinuation): mixed: hypothetical 10, not stated 7, treatment_policy 1
- NoteOutcome assessment, intercurrent events (rescue): mixed: hypothetical 16, not stated 2
- NoteRisk of bias, blinding: mixed: double_blind 12, open_label 5, single_blind 1
- NoteData handling, input conversions: arms_combined 9
| Trial | time weeks | analysis set | definition | instrument | adjudicated | proportion method | intercurrent events (discontinuation) | intercurrent events (rescue) | blinding | funding | start year | Eligibility |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT03131687 | 26 | modified_itt | not stated | not stated | not stated | not stated | treatment_policy | hypothetical | double_blind | industry | 2017 | age 18 to 75; T2D at least 6 months; HbA1c 7.0 to 10.5%; BMI 23 to 50; diet and exercise or metformin |
| PIONEER 4 | 26 | full_analysis | not stated | not stated | not stated | not stated | hypothetical | hypothetical | double_blind | industry | 2016 | Age 18 or older; T2D on metformin with or without SGLT2i; HbA1c 7.0 to 9.5 percent; eGFR 60 or more |
| NCT01476475 | 24 | modified_itt | not stated | not stated | not stated | not stated | hypothetical | hypothetical | open_label | industry | 2011 | Adults with T2D; HbA1c 7 to 10 percent on metformin at least 1.5 g/day; insulin naive |
| PIONEER 10 | 26 | full_analysis | not stated | not stated | not stated | not stated | hypothetical | hypothetical | single_blind | industry | 2017 | Japanese adults 20 or older; T2D; HbA1c 7.0 to 10.5 percent on one oral glucose lowering drug |
| NCT01584232 | 26 | full_analysis | not stated | not stated | not stated | not stated | not stated | hypothetical | open_label | industry | 2012 | Japanese adults 20 years or older; BMI 18.5 to less than 35 kg/m2; HbA1c 7.0 to 10.0 percent; on sulfonylurea and/or biguanide |
| AWARD-10 | 24 | modified_itt | not stated | not stated | not stated | not stated | not stated | hypothetical | double_blind | industry | 2015 | T2D; HbA1c 7.0 to 9.5 percent; BMI 45 or lower; SGLT2i with or without metformin |
| NCT00976937 | 24 | modified_itt | not stated | not stated | not stated | not stated | hypothetical | hypothetical | double_blind | industry | 2009 | age 18 to under 50; BMI 30 or more; HbA1c 7.0 to 10 percent; metformin at least 1.5 g/day |
| SUSTAIN 9 | 30 | full_analysis | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2017 | adults 18 or older (20 in Japan); HbA1c 7.0 to 10.5 percent; stable SGLT2i with or without metformin or SU |
| PIONEER 12 | 26 | full_analysis | not stated | not stated | not stated | not stated | hypothetical | hypothetical | double_blind | industry | 2019 | adults with type 2 diabetes on metformin, HbA1c 7.0 to 10.5 percent |
| AWARD-8 | 24 | modified_itt | not stated | not stated | not stated | not stated | not stated | hypothetical | double_blind | industry | 2013 | age 18 or older; BMI up to 45; HbA1c 7.5 to 9.5 percent on sulfonylurea at least half maximal dose |
| LIRA-SWITCH™ | 26 | full_analysis | not stated | not stated | not stated | not stated | hypothetical | hypothetical | double_blind | industry | 2013 | age 18 or more; HbA1c 7.5 to 9.5 percent; BMI 20 or more; on sitagliptin 100 mg and metformin for 90 days or more |
| AWARD-2 | 26 | modified_itt | not stated | not stated | not stated | not stated | not stated | hypothetical | open_label | industry | 2010 | type 2 diabetes on metformin and glimepiride |
| AWARD-6 | 26 | modified_itt | change in HbA1c from baseline | not stated | not stated | not stated | not stated | not stated | open_label | industry | 2012 | adults; HbA1c 7 to 10 percent; metformin 1500 mg/day or more |
| SUSTAIN | 30 | full_analysis | not stated | not stated | not stated | not stated | hypothetical | hypothetical | double_blind | industry | 2017 | Adults 18 or older, HbA1c 7.0 to 10.5 percent on metformin monotherapy, eGFR 60 or more |
| LIXILAN JP-O1 | 26 | modified_itt | change in HbA1c from baseline to week 26, LOCF | not stated | not stated | not stated | hypothetical | hypothetical | open_label | industry | 2016 | insulin naive Japanese adults; HbA1c 7.5 to 10%; FPG 13.8 mmol/L or less; one or two OADs |
| AWARD-1 | 26 | modified_itt | not stated | not stated | not stated | not stated | not stated | hypothetical | double_blind | industry | 2010 | adults with type 2 diabetes on metformin and pioglitazone |
| GETGOAL-M | 24 | modified_itt | not stated | not stated | not stated | not stated | hypothetical | hypothetical | double_blind | industry | 2008 | type 2 diabetes on metformin 1.5 g/day or more for 3 months; HbA1c 7 to 10 percent; FPG 13.9 mmol/L or less |
| PIONEER 3 | 26 | full_analysis | not stated | not stated | not stated | not stated | hypothetical | hypothetical | double_blind | industry | 2016 | adults with T2D; HbA1c 7.0 to 10.5 percent; metformin with or without sulfonylurea |
Trial data
| Trial | Arm | Treatment | Week | Data | Value | SE | Events / N | Flags | Source |
|---|---|---|---|---|---|---|---|---|---|
| NCT03131687 | A1 | PLACEBO | 26 | arm, change | -0.400 | 0.810 | 41 | R0016215:Supplement Table 1 | |
| NCT03131687 | A2+A3+A4+A5 | TIRZ_SC | 26 | arm, change | -6.130 | 0.498 | 171 | arms_combined | R0016215:Supplement Table 1 |
| NCT03131687 | A6 | DULA_SC | 26 | arm, change | -2.700 | 0.780 | 47 | R0016215:Supplement Table 1 | |
| PIONEER 4 | A1 | SEMA_PO | 26 | arm, change | -4.700 | 0.255 | 285 | registry:outcomes | |
| PIONEER 4 | A2 | LIRA_SC | 26 | arm, change | -3.300 | 0.220 | 284 | registry:outcomes | |
| PIONEER 4 | A3 | PLACEBO | 26 | arm, change | -0.700 | 0.260 | 142 | registry:outcomes | |
| NCT01476475 | A1 | IGLARLIXI_SC | 24 | arm, change | -0.970 | 0.289 | 159 | registry:outcomes | |
| NCT01476475 | A2 | INS_GLARGINE | 24 | arm, change | 0.480 | 0.282 | 160 | registry:outcomes | |
| PIONEER 10 | A1+A2+A3 | SEMA_PO | 26 | arm, change | -1.182 | 0.124 | 370 | arms_combined | R0018421:Figure 3D |
| PIONEER 10 | A4 | DULA_SC | 26 | arm, change | 0.300 | 0.300 | 64 | R0018421:Figure 3D | |
| NCT01584232 | A1 | DULA_SC | 26 | arm, change | -0.480 | 0.170 | 180 | R0016159:Table 2 | |
| NCT01584232 | A2 | INS_GLARGINE | 26 | arm, change | 0.940 | 0.170 | 180 | R0016159:Table 2 | |
| AWARD-10 | A1+A2 | DULA_SC | 24 | arm, change | -2.851 | 0.212 | 283 | arms_combined | registry:outcomes |
| AWARD-10 | A3 | PLACEBO | 24 | arm, change | -2.300 | 0.310 | 140 | registry:outcomes | |
| NCT00976937 | A1 | LIXI_SC | 24 | arm, change | -2.510 | 0.294 | 152 | registry:outcomes | |
| NCT00976937 | A2 | SITAGLIPTIN | 24 | arm, change | -1.170 | 0.304 | 160 | registry:outcomes | |
| SUSTAIN 9 | A1 | SEMA_SC | 30 | contrast, md | -3.810 | 0.452 | R0021710:Figure 3b | ||
| SUSTAIN 9 | A2 | PLACEBO | 30 | contrast, md | R0021710:Figure 3b | ||||
| PIONEER 12 | A1+A2+A3 | SEMA_PO | 26 | arm, change | -2.674 | 0.113 | 941 | arms_combined | registry:outcomes |
| PIONEER 12 | A4 | SITAGLIPTIN | 26 | arm, change | -0.500 | 0.142 | 335 | registry:outcomes | |
| AWARD-8 | A1 | DULA_SC | 24 | arm, change | -0.910 | 0.210 | 212 | R0016038:Results | |
| AWARD-8 | A2 | PLACEBO | 24 | arm, change | -0.240 | 0.400 | 53 | R0016038:Results | |
| LIRA-SWITCH™ | A1 | LIRA_SC | 26 | contrast, md | -1.670 | 0.344 | R0025720:Results | ||
| LIRA-SWITCH™ | A2 | SITAGLIPTIN | 26 | contrast, md | R0025720:Results | ||||
| AWARD-2 | A1+A2 | DULA_SC | 26 | arm, change | -1.646 | 0.141 | 542 | arms_combined | registry:outcomes |
| AWARD-2 | A3 | INS_GLARGINE | 26 | arm, change | 1.010 | 0.200 | 259 | registry:outcomes | |
| AWARD-6 | A1 | DULA_SC | 26 | arm, change | -2.900 | 0.220 | 299 | registry:outcomes | |
| AWARD-6 | A2 | LIRA_SC | 26 | arm, change | -3.610 | 0.220 | 299 | registry:outcomes | |
| SUSTAIN | A1+A2 | SEMA_SC | 30 | arm, change | -3.601 | 0.174 | 477 | arms_combined | registry:outcomes |
| SUSTAIN | A3 | SITAGLIPTIN | 30 | arm, change | -0.400 | 0.157 | 253 | registry:outcomes | |
| LIXILAN JP-O1 | A1 | IGLARLIXI_SC | 26 | arm, change | 0.620 | 0.177 | 161 | R0015751:Table 2 | |
| LIXILAN JP-O1 | A2 | LIXI_SC | 26 | arm, change | -1.320 | 0.180 | 157 | R0015751:Table 2 | |
| AWARD-1 | A1+A2 | DULA_SC | 26 | arm, change | -0.589 | 0.180 | 512 | arms_combined | registry:outcomes |
| AWARD-1 | A3 | EXEN_SC | 26 | arm, change | -1.140 | 0.260 | 245 | registry:outcomes | |
| AWARD-1 | A4 | PLACEBO | 26 | arm, change | 1.370 | 0.370 | 109 | registry:outcomes | |
| GETGOAL-M | A1+A2 | LIXI_SC | 24 | arm, change | -2.000 | 0.166 | 497 | arms_combined | R0025872:Results |
| GETGOAL-M | A3 | PLACEBO | 24 | arm, change | -1.600 | 0.270 | 168 | R0025872:Results | |
| PIONEER 3 | A1+A2+A3 | SEMA_PO | 26 | arm, change | -2.199 | 0.102 | 1,396 | arms_combined | registry:outcomes |
| PIONEER 3 | A4 | SITAGLIPTIN | 26 | arm, change | -0.600 | 0.148 | 467 | registry:outcomes |
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