Network meta-analysis
Body weight change in kilograms (diabetes)
Type 2 diabetes (adults); background therapy: no glucose lowering drug (lifestyle only)
weeks 20 to 36 (target week 26)Not stated by the trialsDoses of a drug pooledMean difference
9
Randomized trials
13
Treatments
2,772
Participants
23
Trial arms
In plain language
Across 9 trials with 2,772 participants, 0 of 12 treatments had a clearly better result than placebo on body weight change in kilograms (diabetes), and for 12 the evidence could not tell them apart from placebo. The most favorable estimate was for Metformin: mean difference -5.64 kg (95% credible interval -10.93 to 1.07).
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
Each circle is a treatment; each line joins treatments that were randomized against each other in at least one trial.
Effects compared with Placebo
Mean difference in kg. Lower values favor the treatment.
| Treatment | Bayesian MD (95% CrI) | 95% prediction interval | Frequentist MD (95% CI) | Verdict |
|---|---|---|---|---|
| Metformin METFORMIN | -5.64 (-10.93 to 1.07) | -12.25 to 3.43 | -8.05 (-13.16 to -2.95) | Unclear |
| Exenatide extended release injection EXENER_SC | -5.57 (-11.64 to 2.55) | -13.00 to 4.01 | -8.05 (-13.39 to -2.72) | Unclear |
| Sitagliptin SITAGLIPTIN | -4.34 (-10.48 to 3.57) | -11.63 to 5.51 | -6.85 (-12.21 to -1.50) | Unclear |
| Semaglutide injection SEMA_SC | -3.24 (-7.67 to 2.08) | -9.84 to 4.13 | -3.29 (-4.95 to -1.63) | Unclear |
| Pioglitazone PIOGLITAZONE | -2.13 (-8.40 to 6.08) | -9.60 to 7.79 | -4.55 (-9.91 to 0.80) | Unclear |
| Ecnoglutide injection ECNO_SC | -2.05 (-6.86 to 3.10) | -8.88 to 5.35 | -2.07 (-3.75 to -0.39) | Unclear |
| Efpe sc EFPE_SC | -1.37 (-6.08 to 3.58) | -8.12 to 5.66 | -1.38 (-3.23 to 0.47) | Unclear |
| Semaglutide tablet SEMA_PO | -0.29 (-4.00 to 5.18) | -6.00 to 7.81 | -0.49 (-1.94 to 0.97) | Unclear |
| Albiglutide injection ALBI_SC | 1.06 (-2.69 to 6.12) | -4.93 to 8.45 | 0.89 (-0.51 to 2.30) | Unclear |
| Liraglutide injection LIRA_SC | 1.11 (-1.02 to 6.05) | -3.46 to 8.65 | 0.68 (-0.43 to 1.79) | Unclear |
| Gliclazide GLICLAZIDE | 2.60 (-4.65 to 10.87) | -5.77 to 12.64 | 1.00 (-5.43 to 7.44) | Unclear |
| Glibenclamide GLIBENCLAMIDE | 3.06 (-1.20 to 10.23) | -2.93 to 12.12 | 2.59 (0.71 to 4.47) | Unclear |
Ranking
How likely each treatment is to be among the best. Rankings ignore the size of differences and their certainty, so read them with the effects above.
League table
Every treatment against every other: mean difference of the row treatment versus the column treatment, posterior median and 95% credible interval. Green: row clearly better; red: row clearly worse.
| Row versus column | PLACEBO | METFORMIN | EXENER_SC | SITAGLIPTIN | SEMA_SC | PIOGLITAZONE | ECNO_SC | EFPE_SC | SEMA_PO | ALBI_SC | LIRA_SC | GLICLAZIDE | GLIBENCLAMIDE |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PLACEBO | PLACEBO | 5.64 -1.07 to 10.93 | 5.57 -2.55 to 11.64 | 4.34 -3.57 to 10.48 | 3.24 -2.08 to 7.67 | 2.13 -6.08 to 8.40 | 2.05 -3.10 to 6.86 | 1.37 -3.58 to 6.08 | 0.29 -5.18 to 4.00 | -1.06 -6.12 to 2.69 | -1.11 -6.05 to 1.02 | -2.60 -10.87 to 4.65 | -3.06 -10.23 to 1.20 |
| METFORMIN | -5.64 -10.93 to 1.07 | METFORMIN | -0.11 -5.08 to 4.71 | -1.28 -6.22 to 3.28 | -2.49 -9.24 to 5.85 | -3.56 -8.52 to 1.14 | -3.73 -10.47 to 5.09 | -4.33 -11.08 to 4.24 | -5.52 -11.81 to 1.71 | -6.84 -12.88 to 0.24 | -6.97 -12.21 to -1.65 | -8.18 -15.64 to -0.55 | -8.97 -15.76 to -1.95 |
| EXENER_SC | -5.57 -11.64 to 2.55 | 0.11 -4.71 to 5.08 | EXENER_SC | -1.20 -5.97 to 3.68 | -2.42 -9.80 to 7.25 | -3.46 -8.20 to 1.65 | -3.62 -10.94 to 6.13 | -4.23 -11.34 to 5.18 | -5.45 -12.62 to 3.14 | -6.80 -13.59 to 1.57 | -6.91 -13.32 to 0.06 | -8.08 -16.43 to 0.99 | -8.90 -16.66 to -0.63 |
| SITAGLIPTIN | -4.34 -10.48 to 3.57 | 1.28 -3.28 to 6.22 | 1.20 -3.68 to 5.97 | SITAGLIPTIN | -1.19 -8.46 to 8.16 | -2.26 -7.10 to 2.65 | -2.41 -9.81 to 7.25 | -3.05 -10.34 to 6.38 | -4.23 -11.53 to 4.07 | -5.58 -12.40 to 2.60 | -5.69 -12.15 to 1.00 | -6.86 -15.36 to 1.75 | -7.65 -15.35 to 0.52 |
| SEMA_SC | -3.24 -7.67 to 2.08 | 2.49 -5.85 to 9.24 | 2.42 -7.25 to 9.80 | 1.19 -8.16 to 8.46 | SEMA_SC | -1.02 -10.51 to 6.48 | -1.20 -7.97 to 6.12 | -1.87 -8.48 to 5.16 | -2.98 -10.34 to 3.10 | -4.30 -11.28 to 2.03 | -4.33 -11.62 to 0.32 | -5.81 -15.13 to 2.67 | -6.28 -15.19 to 0.01 |
| PIOGLITAZONE | -2.13 -8.40 to 6.08 | 3.56 -1.14 to 8.52 | 3.46 -1.65 to 8.20 | 2.26 -2.65 to 7.10 | 1.02 -6.48 to 10.51 | PIOGLITAZONE | -0.17 -7.67 to 9.50 | -0.79 -8.20 to 8.90 | -1.99 -9.11 to 6.55 | -3.32 -10.23 to 5.14 | -3.44 -9.88 to 3.37 | -4.68 -13.04 to 4.20 | -5.42 -13.22 to 2.67 |
| ECNO_SC | -2.05 -6.86 to 3.10 | 3.73 -5.09 to 10.47 | 3.62 -6.13 to 10.94 | 2.41 -7.25 to 9.81 | 1.20 -6.12 to 7.97 | 0.17 -9.50 to 7.67 | ECNO_SC | -0.66 -7.42 to 6.16 | -1.75 -9.04 to 4.12 | -3.11 -10.33 to 2.89 | -3.12 -10.56 to 1.62 | -4.52 -14.51 to 3.79 | -5.08 -14.24 to 0.94 |
| EFPE_SC | -1.37 -6.08 to 3.58 | 4.33 -4.24 to 11.08 | 4.23 -5.18 to 11.34 | 3.05 -6.38 to 10.34 | 1.87 -5.16 to 8.48 | 0.79 -8.90 to 8.20 | 0.66 -6.16 to 7.42 | EFPE_SC | -1.12 -8.35 to 4.70 | -2.46 -9.49 to 3.45 | -2.52 -9.57 to 2.08 | -3.91 -13.60 to 4.28 | -4.50 -13.35 to 1.64 |
| SEMA_PO | -0.29 -4.00 to 5.18 | 5.52 -1.71 to 11.81 | 5.45 -3.14 to 12.62 | 4.23 -4.07 to 11.53 | 2.98 -3.10 to 10.34 | 1.99 -6.55 to 9.11 | 1.75 -4.12 to 9.04 | 1.12 -4.70 to 8.35 | SEMA_PO | -1.36 -7.27 to 4.99 | -1.35 -6.56 to 2.62 | -2.68 -11.15 to 5.35 | -3.32 -10.47 to 2.58 |
| ALBI_SC | 1.06 -2.69 to 6.12 | 6.84 -0.24 to 12.88 | 6.80 -1.57 to 13.59 | 5.58 -2.60 to 12.40 | 4.30 -2.03 to 11.28 | 3.32 -5.14 to 10.23 | 3.11 -2.89 to 10.33 | 2.46 -3.45 to 9.49 | 1.36 -4.99 to 7.27 | ALBI_SC | 0.01 -5.45 to 3.64 | -1.33 -9.96 to 6.38 | -1.98 -9.38 to 3.85 |
| LIRA_SC | 1.11 -1.02 to 6.05 | 6.97 1.65 to 12.21 | 6.91 -0.06 to 13.32 | 5.69 -1.00 to 12.15 | 4.33 -0.32 to 11.62 | 3.44 -3.37 to 9.88 | 3.12 -1.62 to 10.56 | 2.52 -2.08 to 9.57 | 1.35 -2.62 to 6.56 | -0.01 -3.64 to 5.45 | LIRA_SC | -1.18 -8.33 to 6.04 | -1.96 -6.95 to 2.85 |
| GLICLAZIDE | 2.60 -4.65 to 10.87 | 8.18 0.55 to 15.64 | 8.08 -0.99 to 16.43 | 6.86 -1.75 to 15.36 | 5.81 -2.67 to 15.13 | 4.68 -4.20 to 13.04 | 4.52 -3.79 to 14.51 | 3.91 -4.28 to 13.60 | 2.68 -5.35 to 11.15 | 1.33 -6.38 to 9.96 | 1.18 -6.04 to 8.33 | GLICLAZIDE | -0.84 -9.10 to 7.64 |
| GLIBENCLAMIDE | 3.06 -1.20 to 10.23 | 8.97 1.95 to 15.76 | 8.90 0.63 to 16.66 | 7.65 -0.52 to 15.35 | 6.28 -0.01 to 15.19 | 5.42 -2.67 to 13.22 | 5.08 -0.94 to 14.24 | 4.50 -1.64 to 13.35 | 3.32 -2.58 to 10.47 | 1.98 -3.85 to 9.38 | 1.96 -2.85 to 6.95 | 0.84 -7.64 to 9.10 | GLIBENCLAMIDE |
Heterogeneity, fit and convergence
Bayesian random effects (primary)
Frequentist check (netmeta)
Inconsistency
Do trials comparing two treatments directly agree with the indirect evidence through other treatments?
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
A comparison adjusted funnel plot: each point is one trial comparison, centered on its own network estimate. Asymmetry can signal that small trials with unfavorable results are missing.
Fewer than ten trial comparisons, too few to judge funnel plot asymmetry.
Baseline characteristics of the trials
The baseline value of each effect modifier or prognostic factor that applies here, per trial: mean or percent over arms, weighted by the number randomized. A note under a value names a stand in (a median for a mean, 100 minus the male share, Asian subgroup rows, an all Asian site list); "not reported" means no source of the trial prints it.
| Trial | Sex (percent female) effect modifier, prognostic factor; 8 of 9 | Baseline BMI or body weight (kg/m2) effect modifier, prognostic factor; 9 of 9 | Background glucose lowering therapy (stratum S0 to S4) effect modifier, prognostic factor; 9 of 9 | Asian ancestry or region (percent Asian) effect modifier, prognostic factor; 6 of 9 | Kidney function (eGFR) (mL/min/1.73 m2) prognostic factor, effect modifier; 4 of 9 | Treatment duration (weeks) effect modifier; 9 of 9 | Lifestyle co-intervention intensity (none standard intensive) effect modifier, prognostic factor; 9 of 9 |
|---|---|---|---|---|---|---|---|
| PIONEER 9 S001943 | 21.4 | 25.9 | S0 | 100 | 97 | 52 | not_reported |
| NCT03068065 S000048 | 27.96 | 27.46 | S0 | 100 region: all sites in Asia | not reported | 24 | standard |
| NCT00393718 S000330 | 32.75 | 24.8 | S0 | 100 region: all sites in Asia | not reported | 52 | not_reported |
| NCT03010683 S000389 | 33.33 | 30.3 | S0 | not reported | 84 | 26.07 | not_reported |
| SUSTAIN™1 S000878 | 45.62 | 33.2 | S0 | 21.4 | 95.6 | 30 | not_reported |
| NCT01733758 S001075 | not reported | 25.82 | S0 | not reported | not reported | 52 | not_reported |
| NCT00676338 S001966 | 40.99 | 31.21 | S0 | 12.44 Asian subgroup rows | not reported | 26 | standard |
| AMPLITUDE-M S002081 | 46.06 | 34.2 | S0 | not reported | 101.24 | 56 | not_reported |
| S002947 S002947 | 35.85 | 26.25 | S0 | 100 region: all sites in Asia | not reported | 20 | not_reported |
Comparability of the trials
Checked across designs (the set of treatments each trial compares) for eligibility, outcome definition and assessment, and the baseline factors above. Flags point to possible intransitivity; notes describe variation that is not tied to design.
- FlagBaseline, Baseline BMI or body weight: design means range from 24.8 (GLIBENCLAMIDE vs LIRA_SC) to 34.2 (EFPE_SC vs PLACEBO) kg/m2; threshold 3
- FlagBaseline, Sex: design means range from 21.4 (LIRA_SC vs PLACEBO vs SEMA_PO) to 46.1 (EFPE_SC vs PLACEBO) percent female; threshold 15
- FlagBaseline, Asian ancestry or region: not reported by 3 of 9 trials
- FlagBaseline, Asian ancestry or region: design means range from 12.4 (EXENER_SC vs METFORMIN vs PIOGLITAZONE vs SITAGLIPTIN) to 100.0 (ECNO_SC vs PLACEBO) percent Asian; threshold 30
- FlagBaseline, Kidney function (eGFR): not reported by 5 of 9 trials
- FlagBaseline, Kidney function (eGFR): design means range from 84.0 (LIRA_SC vs METFORMIN) to 101.2 (EFPE_SC vs PLACEBO) mL/min/1.73 m2; threshold 15
- FlagBaseline, Treatment duration: design means range from 20.0 (ECNO_SC vs PLACEBO) to 56.0 (EFPE_SC vs PLACEBO) weeks; threshold 26
- NoteOutcome assessment, time point: selected time points span 20 to 30 weeks
- NoteOutcome assessment, analysis set: mixed: completers 1, full_analysis 4, modified_itt 1, randomized 3
- NoteOutcome assessment, intercurrent events (discontinuation): mixed: hypothetical 1, not stated 8
- NoteOutcome assessment, intercurrent events (rescue): mixed: hypothetical 1, not stated 8
- NoteRisk of bias, blinding: mixed: double_blind 7, open_label 1, single_blind 1
- NoteRisk of bias, funding: mixed: industry 7, not_reported 2
- NoteData handling, input conversions: arms_combined 4
| Trial | time weeks | analysis set | definition | instrument | adjudicated | proportion method | intercurrent events (discontinuation) | intercurrent events (rescue) | blinding | funding | start year | Eligibility |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PIONEER 9 | 26 | full_analysis | not stated | not stated | not stated | not stated | hypothetical | hypothetical | double_blind | industry | 2017 | Japanese adults 20 y or older; HbA1c 6.5 to 9.5 on one oral drug washed out, or 7.0 to 10.0 on diet and exercise |
| NCT03068065 | 24 | completers | not stated | not stated | not stated | not stated | not stated | not stated | open_label | not_reported | 2014 | age 18 to 70; drug naive 3 months; HbA1c 7 to 14 percent; BMI 20 to 38; NAFLD on ultrasound |
| NCT00393718 | 24 | full_analysis | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2006 | age 20 or older; HbA1c 7.4 to 10.4 percent NGSP; with or without prior oral agents |
| NCT03010683 | 26.07 | randomized | not stated | not stated | not stated | not stated | not stated | not stated | single_blind | not_reported | 2015 | newly diagnosed treatment naive type 2 diabetes; no cardiovascular, liver or kidney disease |
| SUSTAIN™1 | 30 | full_analysis | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2014 | age 18 or older (20 in Japan); HbA1c 7.0 to 10.0 percent; drug naive on diet and exercise; eGFR 30 or more |
| NCT01733758 | 24 | modified_itt | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2013 | Japanese adults; diet and exercise with or without one oral drug; HbA1c 7 to 10 percent after washout |
| NCT00676338 | 26 | full_analysis | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2008 | adults, HbA1c 7.1 to 11.0 percent, BMI 23 to 45 kg/m2, drug naive |
| AMPLITUDE-M | 30 | randomized | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2017 | type 2 diabetes on diet and exercise, HbA1c 7 to 10 percent, no glucose lowering drug in prior 3 months |
| S002947 | 20 | randomized | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2021 | age 18 to 65; HbA1c 7.0 to 10.5 percent; BMI 20 to 35; diet or one oral agent washed out |
Trial data
What each trial contributes. Arm rows give the arm value with its standard error, or events over participants; contrast rows give the mean difference on the analysis scale against the trial's first row. Flags mark converted, combined or approximated inputs.
| Trial | Arm | Treatment | Week | Data | Value | SE | Events / N | Flags | Source |
|---|---|---|---|---|---|---|---|---|---|
| NCT03068065 | A1 | LIRA_SC | 24 | arm, final | 75.500 | 2.000 | 29 | R0025051:Table 1 | |
| NCT03068065 | A2 | METFORMIN | 24 | arm, final | 71.200 | 2.550 | 29 | R0025051:Table 1 | |
| NCT03068065 | A3 | GLICLAZIDE | 24 | arm, final | 77.540 | 2.570 | 27 | R0025051:Table 1 | |
| NCT00393718 | A1 | LIRA_SC | 24 | arm, final | 64.060 | 0.150 | 265 | registry:outcomes | |
| NCT00393718 | A2 | GLIBENCLAMIDE | 24 | arm, final | 65.970 | 0.200 | 130 | registry:outcomes | |
| NCT03010683 | A1 | LIRA_SC | 26.07 | arm, final | 92.000 | 2.921 | 30 | R0016601:Table 2 | |
| NCT03010683 | A2 | METFORMIN | 26.07 | arm, final | 77.000 | 2.556 | 30 | R0016601:Table 2 | |
| SUSTAIN™1 | A1+A2 | SEMA_SC | 30 | arm, change | -4.179 | 0.291 | 258 | arms_combined | registry:outcomes |
| SUSTAIN™1 | A3 | PLACEBO | 30 | arm, change | -0.890 | 0.305 | 129 | registry:outcomes | |
| NCT01733758 | A1 | PLACEBO | 24 | arm, change | -0.500 | 0.194 | 77 | registry:outcomes | |
| NCT01733758 | A2+A3 | ALBI_SC | 24 | arm, change | 0.145 | 0.108 | 309 | arms_combined | registry:outcomes |
| NCT01733758 | A4 | LIRA_SC | 24 | arm, change | -0.340 | 0.255 | 103 | registry:outcomes | |
| PIONEER 9 | A1+A2+A3 | SEMA_PO | 26 | arm, change | -1.326 | 0.202 | 146 | arms_combined | registry:outcomes |
| PIONEER 9 | A4 | LIRA_SC | 26 | arm, change | 0.100 | 0.231 | 48 | registry:outcomes | |
| PIONEER 9 | A5 | PLACEBO | 26 | arm, change | -1.100 | 0.229 | 49 | registry:outcomes | |
| NCT00676338 | A1 | EXENER_SC | 26 | arm, change | -2.000 | 0.200 | 215 | R0027761:Results | |
| NCT00676338 | A2 | METFORMIN | 26 | arm, change | -2.000 | 0.200 | 217 | R0027761:Results | |
| NCT00676338 | A3 | PIOGLITAZONE | 26 | arm, change | 1.500 | 0.300 | 134 | R0027761:Results | |
| NCT00676338 | A4 | SITAGLIPTIN | 26 | arm, change | -0.800 | 0.300 | 141 | R0027761:Results | |
| AMPLITUDE-M | A1+A2+A3 | EFPE_SC | 30 | arm, change | -2.578 | 0.316 | 304 | arms_combined | R0007136:Figure 2 |
| AMPLITUDE-M | A4 | PLACEBO | 30 | arm, change | -1.200 | 0.500 | 102 | R0007136:Figure 2 | |
| S002947 | A1 | ECNO_SC | 20 | contrast, md | -2.070 | 0.439 | R0006482:Figure 4 | ||
| S002947 | A4 | PLACEBO | 20 | contrast, md | R0006482:Figure 4 |
Rerun this analysis yourself
Remove treatments or trials and refit the frequentist and Bayesian models in your browser, with the same methods as the published analysis.