Network meta-analysis
Body weight change in kilograms (diabetes)
Type 2 diabetes (adults); background therapy: no glucose lowering drug (lifestyle only)
weeks 36 to 64 (target week 52)Hypothetical (as if everyone stayed on treatment)Each dose separatelyMean difference
6
Randomized trials
13
Treatments
3,091
Participants
20
Trial arms
In plain language
Across 6 trials with 3,091 participants, 5 of 12 treatments had a clearly better result than placebo on body weight change in kilograms (diabetes), and for 7 the evidence could not tell them apart from placebo. The most favorable estimate was for tirzepatide 15 mg subcutaneous once weekly: mean difference -9.15 kg (95% credible interval -12.07 to -5.43).
- Tirzepatide 15 mg subcutaneous once weekly: among the most effective (certainty pending).
- Tirzepatide 10 mg subcutaneous once weekly: better than placebo but not among the most effective (certainty pending).
- Orforglipron 36 mg oral once daily: better than placebo but not among the most effective (certainty pending).
- Tirzepatide 5 mg subcutaneous once weekly: better than placebo but not among the most effective (certainty pending).
- Orforglipron 12 mg oral once daily: better than placebo but not among the most effective (certainty pending).
- Orforglipron 3 mg oral once daily: not convincingly different from placebo (certainty pending).
- Metformin: not convincingly different from placebo (certainty pending).
- Dulaglutide 1.5 mg subcutaneous once weekly: not convincingly different from placebo (certainty pending).
- Albiglutide 50 mg subcutaneous once weekly: not convincingly different from placebo (certainty pending).
- Albiglutide 30 mg subcutaneous once weekly: not convincingly different from placebo (certainty pending).
- Dulaglutide 0.75 mg subcutaneous once weekly: not convincingly different from placebo (certainty pending).
- Liraglutide 0.9 mg injection once daily: not convincingly different from placebo (certainty pending).
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 | Confidence |
|---|---|---|---|---|---|
| Tirzepatide 15 mg subcutaneous once weekly TIRZ_SC_15MG_QW | -9.15 (-12.07 to -5.43) | -13.51 to -3.67 | -9.33 (-11.57 to -7.09) | Better | pending |
| Tirzepatide 10 mg subcutaneous once weekly TIRZ_SC_10MG_QW | -7.18 (-10.06 to -3.47) | -11.57 to -1.92 | -7.36 (-9.60 to -5.12) | Better | pending |
| Orforglipron 36 mg oral once daily ORFO_PO_36MG_QD | -5.91 (-9.26 to -1.92) | -10.77 to -0.61 | -6.00 (-8.33 to -3.67) | Better | pending |
| Tirzepatide 5 mg subcutaneous once weekly TIRZ_SC_5MG_QW | -5.33 (-8.23 to -1.72) | -9.84 to -0.45 | -5.53 (-7.77 to -3.29) | Better | pending |
| Orforglipron 12 mg oral once daily ORFO_PO_12MG_QD | -4.09 (-7.42 to -0.26) | -8.91 to 1.20 | -4.20 (-6.48 to -1.92) | Better | pending |
| Orforglipron 3 mg oral once daily ORFO_PO_3MG_QD | -3.02 (-6.44 to 0.90) | -7.92 to 2.39 | -3.10 (-5.33 to -0.87) | Unclear | pending |
| Metformin METFORMIN | -0.55 (-5.25 to 5.13) | -6.62 to 6.24 | -0.68 (-4.13 to 2.76) | Unclear | pending |
| Dulaglutide 1.5 mg subcutaneous once weekly DULA_SC_1p5MG_QW | -0.27 (-4.86 to 5.24) | -5.90 to 6.12 | -0.41 (-3.86 to 3.03) | Unclear | pending |
| Albiglutide 50 mg subcutaneous once weekly ALBI_SC_50MG_QW | -0.22 (-3.75 to 3.42) | -5.34 to 4.84 | -0.20 (-2.48 to 2.08) | Unclear | pending |
| Albiglutide 30 mg subcutaneous once weekly ALBI_SC_30MG_QW | 0.26 (-3.33 to 3.85) | -4.97 to 5.39 | 0.27 (-2.00 to 2.54) | Unclear | pending |
| Dulaglutide 0.75 mg subcutaneous once weekly DULA_SC_0p75MG_QW | 0.59 (-2.85 to 4.93) | -4.17 to 6.20 | 0.43 (-2.30 to 3.16) | Unclear | pending |
| Liraglutide 0.9 mg injection once daily LIRA_SC_0p9MG_QD | 0.64 (-4.09 to 6.11) | -5.24 to 7.20 | 0.47 (-2.94 to 3.87) | Unclear | pending |
Confidence in the results
How much each comparison can be trusted, rated with CINeMA in six domains and summarized with GRADE.
| Comparison | Within study bias | Reporting bias | Indirectness | Imprecision | Heterogeneity | Incoherence | Confidence |
|---|---|---|---|---|---|---|---|
| Albiglutide 30 mg subcutaneous once weekly versus Placebo | pending | some | pending | major | none | some | pending |
| Albiglutide 50 mg subcutaneous once weekly versus Placebo | pending | some | pending | major | none | some | pending |
| Dulaglutide 0.75 mg subcutaneous once weekly versus Placebo | pending | some | pending | major | none | some | pending |
| Dulaglutide 1.5 mg subcutaneous once weekly versus Placebo | pending | some | pending | major | none | some | pending |
| Liraglutide 0.9 mg injection once daily versus Placebo | pending | some | pending | major | none | some | pending |
| Metformin versus Placebo | pending | some | pending | major | none | some | pending |
| Orforglipron 3 mg oral once daily versus Placebo | pending | some | pending | some | some | some | pending |
| Orforglipron 12 mg oral once daily versus Placebo | pending | some | pending | some | none | some | pending |
| Orforglipron 36 mg oral once daily versus Placebo | pending | some | pending | some | none | some | pending |
| Tirzepatide 5 mg subcutaneous once weekly versus Placebo | pending | some | pending | some | none | some | pending |
| Tirzepatide 10 mg subcutaneous once weekly versus Placebo | pending | some | pending | none | some | some | pending |
| Tirzepatide 15 mg subcutaneous once weekly versus Placebo | pending | some | pending | none | none | some | pending |
Every other comparison (66)
| Comparison | Within study bias | Reporting bias | Indirectness | Imprecision | Heterogeneity | Incoherence | Confidence |
|---|---|---|---|---|---|---|---|
| Albiglutide 30 mg subcutaneous once weekly versus Albiglutide 50 mg subcutaneous once weekly | pending | some | pending | major | none | some | pending |
| Albiglutide 30 mg subcutaneous once weekly versus Dulaglutide 0.75 mg subcutaneous once weekly | pending | some | pending | major | none | some | pending |
| Albiglutide 50 mg subcutaneous once weekly versus Dulaglutide 0.75 mg subcutaneous once weekly | pending | some | pending | major | none | some | pending |
| Albiglutide 30 mg subcutaneous once weekly versus Dulaglutide 1.5 mg subcutaneous once weekly | pending | some | pending | major | none | some | pending |
| Albiglutide 50 mg subcutaneous once weekly versus Dulaglutide 1.5 mg subcutaneous once weekly | pending | some | pending | major | none | some | pending |
| Dulaglutide 0.75 mg subcutaneous once weekly versus Dulaglutide 1.5 mg subcutaneous once weekly | pending | some | pending | major | none | some | pending |
| Albiglutide 30 mg subcutaneous once weekly versus Liraglutide 0.9 mg injection once daily | pending | some | pending | major | none | some | pending |
| Albiglutide 50 mg subcutaneous once weekly versus Liraglutide 0.9 mg injection once daily | pending | some | pending | major | none | some | pending |
| Dulaglutide 0.75 mg subcutaneous once weekly versus Liraglutide 0.9 mg injection once daily | pending | some | pending | major | none | some | pending |
| Dulaglutide 1.5 mg subcutaneous once weekly versus Liraglutide 0.9 mg injection once daily | pending | some | pending | major | none | some | pending |
| Albiglutide 30 mg subcutaneous once weekly versus Metformin | pending | some | pending | major | none | some | pending |
| Albiglutide 50 mg subcutaneous once weekly versus Metformin | pending | some | pending | major | none | some | pending |
| Dulaglutide 0.75 mg subcutaneous once weekly versus Metformin | pending | some | pending | major | none | some | pending |
| Dulaglutide 1.5 mg subcutaneous once weekly versus Metformin | pending | some | pending | major | none | some | pending |
| Liraglutide 0.9 mg injection once daily versus Metformin | pending | some | pending | major | none | some | pending |
| Albiglutide 30 mg subcutaneous once weekly versus Orforglipron 3 mg oral once daily | pending | some | pending | some | some | some | pending |
| Albiglutide 50 mg subcutaneous once weekly versus Orforglipron 3 mg oral once daily | pending | some | pending | major | none | some | pending |
| Dulaglutide 0.75 mg subcutaneous once weekly versus Orforglipron 3 mg oral once daily | pending | some | pending | some | some | some | pending |
| Dulaglutide 1.5 mg subcutaneous once weekly versus Orforglipron 3 mg oral once daily | pending | some | pending | major | none | some | pending |
| Liraglutide 0.9 mg injection once daily versus Orforglipron 3 mg oral once daily | pending | some | pending | major | none | some | pending |
| Metformin versus Orforglipron 3 mg oral once daily | pending | some | pending | major | none | some | pending |
| Orforglipron 12 mg oral once daily versus Orforglipron 3 mg oral once daily | pending | some | pending | major | none | some | pending |
| Orforglipron 36 mg oral once daily versus Orforglipron 3 mg oral once daily | pending | some | pending | some | some | some | pending |
| Albiglutide 30 mg subcutaneous once weekly versus Orforglipron 12 mg oral once daily | pending | some | pending | some | some | some | pending |
| Albiglutide 50 mg subcutaneous once weekly versus Orforglipron 12 mg oral once daily | pending | some | pending | some | some | some | pending |
| Dulaglutide 0.75 mg subcutaneous once weekly versus Orforglipron 12 mg oral once daily | pending | some | pending | some | none | some | pending |
| Dulaglutide 1.5 mg subcutaneous once weekly versus Orforglipron 12 mg oral once daily | pending | some | pending | some | some | some | pending |
| Liraglutide 0.9 mg injection once daily versus Orforglipron 12 mg oral once daily | pending | some | pending | some | some | some | pending |
| Metformin versus Orforglipron 12 mg oral once daily | pending | some | pending | major | none | some | pending |
| Albiglutide 30 mg subcutaneous once weekly versus Orforglipron 36 mg oral once daily | pending | some | pending | some | none | some | pending |
| Albiglutide 50 mg subcutaneous once weekly versus Orforglipron 36 mg oral once daily | pending | some | pending | some | none | some | pending |
| Dulaglutide 0.75 mg subcutaneous once weekly versus Orforglipron 36 mg oral once daily | pending | some | pending | some | none | some | pending |
| Dulaglutide 1.5 mg subcutaneous once weekly versus Orforglipron 36 mg oral once daily | pending | some | pending | some | none | some | pending |
| Liraglutide 0.9 mg injection once daily versus Orforglipron 36 mg oral once daily | pending | some | pending | some | none | some | pending |
| Metformin versus Orforglipron 36 mg oral once daily | pending | some | pending | some | none | some | pending |
| Orforglipron 12 mg oral once daily versus Orforglipron 36 mg oral once daily | pending | some | pending | major | none | some | pending |
| Albiglutide 30 mg subcutaneous once weekly versus Tirzepatide 5 mg subcutaneous once weekly | pending | some | pending | some | none | some | pending |
| Albiglutide 50 mg subcutaneous once weekly versus Tirzepatide 5 mg subcutaneous once weekly | pending | some | pending | some | none | some | pending |
| Dulaglutide 0.75 mg subcutaneous once weekly versus Tirzepatide 5 mg subcutaneous once weekly | pending | some | pending | none | some | some | pending |
| Dulaglutide 1.5 mg subcutaneous once weekly versus Tirzepatide 5 mg subcutaneous once weekly | pending | some | pending | some | none | some | pending |
| Liraglutide 0.9 mg injection once daily versus Tirzepatide 5 mg subcutaneous once weekly | pending | some | pending | some | none | some | pending |
| Metformin versus Tirzepatide 5 mg subcutaneous once weekly | pending | some | pending | some | none | some | pending |
| Orforglipron 3 mg oral once daily versus Tirzepatide 5 mg subcutaneous once weekly | pending | some | pending | major | none | some | pending |
| Orforglipron 12 mg oral once daily versus Tirzepatide 5 mg subcutaneous once weekly | pending | some | pending | major | none | some | pending |
| Orforglipron 36 mg oral once daily versus Tirzepatide 5 mg subcutaneous once weekly | pending | some | pending | major | none | some | pending |
| Tirzepatide 10 mg subcutaneous once weekly versus Tirzepatide 5 mg subcutaneous once weekly | pending | some | pending | some | some | some | pending |
| Tirzepatide 15 mg subcutaneous once weekly versus Tirzepatide 5 mg subcutaneous once weekly | pending | some | pending | some | none | some | pending |
| Albiglutide 30 mg subcutaneous once weekly versus Tirzepatide 10 mg subcutaneous once weekly | pending | some | pending | some | none | some | pending |
| Albiglutide 50 mg subcutaneous once weekly versus Tirzepatide 10 mg subcutaneous once weekly | pending | some | pending | some | none | some | pending |
| Dulaglutide 0.75 mg subcutaneous once weekly versus Tirzepatide 10 mg subcutaneous once weekly | pending | some | pending | none | none | some | pending |
| Dulaglutide 1.5 mg subcutaneous once weekly versus Tirzepatide 10 mg subcutaneous once weekly | pending | some | pending | none | some | some | pending |
| Liraglutide 0.9 mg injection once daily versus Tirzepatide 10 mg subcutaneous once weekly | pending | some | pending | none | some | some | pending |
| Metformin versus Tirzepatide 10 mg subcutaneous once weekly | pending | some | pending | some | none | some | pending |
| Orforglipron 3 mg oral once daily versus Tirzepatide 10 mg subcutaneous once weekly | pending | some | pending | some | some | some | pending |
| Orforglipron 12 mg oral once daily versus Tirzepatide 10 mg subcutaneous once weekly | pending | some | pending | some | some | some | pending |
| Orforglipron 36 mg oral once daily versus Tirzepatide 10 mg subcutaneous once weekly | pending | some | pending | major | none | some | pending |
| Albiglutide 30 mg subcutaneous once weekly versus Tirzepatide 15 mg subcutaneous once weekly | pending | some | pending | none | none | some | pending |
| Albiglutide 50 mg subcutaneous once weekly versus Tirzepatide 15 mg subcutaneous once weekly | pending | some | pending | none | none | some | pending |
| Dulaglutide 0.75 mg subcutaneous once weekly versus Tirzepatide 15 mg subcutaneous once weekly | pending | some | pending | none | none | some | pending |
| Dulaglutide 1.5 mg subcutaneous once weekly versus Tirzepatide 15 mg subcutaneous once weekly | pending | some | pending | none | none | some | pending |
| Liraglutide 0.9 mg injection once daily versus Tirzepatide 15 mg subcutaneous once weekly | pending | some | pending | none | none | some | pending |
| Metformin versus Tirzepatide 15 mg subcutaneous once weekly | pending | some | pending | none | none | some | pending |
| Orforglipron 3 mg oral once daily versus Tirzepatide 15 mg subcutaneous once weekly | pending | some | pending | some | none | some | pending |
| Orforglipron 12 mg oral once daily versus Tirzepatide 15 mg subcutaneous once weekly | pending | some | pending | some | none | some | pending |
| Orforglipron 36 mg oral once daily versus Tirzepatide 15 mg subcutaneous once weekly | pending | some | pending | some | some | some | pending |
| Tirzepatide 10 mg subcutaneous once weekly versus Tirzepatide 15 mg subcutaneous once weekly | pending | some | pending | some | some | some | pending |
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.
Rank probabilities
| Treatment | Rank 1 | Rank 2 | Rank 3 | Rank 4 | Rank 5 | Rank 6 | Rank 7 | Rank 8 | Rank 9 | Rank 10 | Rank 11 | Rank 12 | Rank 13 | Mean rank |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| TIRZ_SC_15MG_QW | 87% | 9% | 2% | 1% | 1.2 | |||||||||
| TIRZ_SC_10MG_QW | 4% | 67% | 19% | 6% | 3% | 1% | 2.4 | |||||||
| ORFO_PO_36MG_QD | 6% | 17% | 36% | 28% | 7% | 3% | 1% | 1% | 3.4 | |||||
| TIRZ_SC_5MG_QW | 3% | 32% | 38% | 16% | 8% | 1% | 1% | 4.0 | ||||||
| ORFO_PO_12MG_QD | 1% | 2% | 6% | 17% | 46% | 16% | 5% | 3% | 2% | 1% | 1% | 5.1 | ||
| ORFO_PO_3MG_QD | 1% | 2% | 5% | 16% | 51% | 10% | 6% | 3% | 3% | 1% | 1% | 1% | 6.2 | |
| METFORMIN | 1% | 2% | 4% | 6% | 22% | 18% | 12% | 12% | 10% | 7% | 6% | 8.7 | ||
| DULA_SC_1p5MG_QW | 1% | 3% | 5% | 15% | 18% | 12% | 13% | 13% | 9% | 10% | 9.2 | |||
| ALBI_SC_50MG_QW | 1% | 2% | 4% | 19% | 15% | 14% | 11% | 11% | 12% | 11% | 9.3 | |||
| PLACEBO | 1% | 10% | 15% | 20% | 17% | 18% | 12% | 7% | 9.8 | |||||
| ALBI_SC_30MG_QW | 1% | 1% | 3% | 10% | 12% | 12% | 12% | 12% | 15% | 22% | 10.2 | |||
| LIRA_SC_0p9MG_QD | 1% | 2% | 3% | 6% | 7% | 10% | 12% | 13% | 16% | 30% | 10.7 | |||
| DULA_SC_0p75MG_QW | 1% | 2% | 5% | 12% | 17% | 20% | 27% | 14% | 10.8 |
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 | TIRZ_SC_15MG_QW | TIRZ_SC_10MG_QW | ORFO_PO_36MG_QD | TIRZ_SC_5MG_QW | ORFO_PO_12MG_QD | ORFO_PO_3MG_QD | METFORMIN | DULA_SC_1p5MG_QW | ALBI_SC_50MG_QW | ALBI_SC_30MG_QW | DULA_SC_0p75MG_QW | LIRA_SC_0p9MG_QD |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PLACEBO | PLACEBO | 9.15 5.43 to 12.07 | 7.18 3.47 to 10.06 | 5.91 1.92 to 9.26 | 5.33 1.72 to 8.23 | 4.09 0.26 to 7.42 | 3.02 -0.90 to 6.44 | 0.55 -5.13 to 5.25 | 0.27 -5.24 to 4.86 | 0.22 -3.42 to 3.75 | -0.26 -3.85 to 3.33 | -0.59 -4.93 to 2.85 | -0.64 -6.11 to 4.09 |
| TIRZ_SC_15MG_QW | -9.15 -12.07 to -5.43 | TIRZ_SC_15MG_QW | -2.00 -4.55 to 0.85 | -3.25 -8.09 to 1.83 | -3.82 -6.33 to -1.04 | -5.04 -9.53 to -0.05 | -6.11 -10.66 to -1.19 | -8.64 -13.36 to -3.83 | -8.91 -13.45 to -4.16 | -8.92 -13.53 to -3.82 | -9.42 -13.76 to -4.03 | -9.76 -12.83 to -6.41 | -9.81 -14.21 to -4.91 |
| TIRZ_SC_10MG_QW | -7.18 -10.06 to -3.47 | 2.00 -0.85 to 4.55 | TIRZ_SC_10MG_QW | -1.30 -5.97 to 3.78 | -1.83 -4.44 to 0.83 | -3.08 -7.72 to 1.92 | -4.14 -8.85 to 0.98 | -6.66 -11.36 to -1.86 | -6.92 -11.64 to -2.32 | -6.95 -11.38 to -1.86 | -7.45 -11.85 to -1.89 | -7.75 -11.01 to -4.47 | -7.77 -12.39 to -3.16 |
| ORFO_PO_36MG_QD | -5.91 -9.26 to -1.92 | 3.25 -1.83 to 8.09 | 1.30 -3.78 to 5.97 | ORFO_PO_36MG_QD | -0.58 -5.34 to 4.16 | -1.82 -5.57 to 2.01 | -2.89 -6.59 to 0.85 | -5.36 -11.68 to 0.83 | -5.64 -11.98 to 0.49 | -5.67 -10.62 to -0.42 | -6.14 -11.20 to -0.83 | -6.50 -11.97 to -1.36 | -6.57 -12.85 to -0.29 |
| TIRZ_SC_5MG_QW | -5.33 -8.23 to -1.72 | 3.82 1.04 to 6.33 | 1.83 -0.83 to 4.44 | 0.58 -4.16 to 5.34 | TIRZ_SC_5MG_QW | -1.22 -5.95 to 3.50 | -2.31 -7.06 to 2.57 | -4.82 -9.40 to -0.21 | -5.09 -9.90 to -0.54 | -5.10 -9.65 to -0.18 | -5.61 -10.05 to -0.47 | -5.94 -9.20 to -2.71 | -5.96 -10.54 to -1.13 |
| ORFO_PO_12MG_QD | -4.09 -7.42 to -0.26 | 5.04 0.05 to 9.53 | 3.08 -1.92 to 7.72 | 1.82 -2.01 to 5.57 | 1.22 -3.50 to 5.95 | ORFO_PO_12MG_QD | -1.07 -4.91 to 2.77 | -3.56 -9.84 to 2.49 | -3.82 -9.95 to 1.95 | -3.87 -8.70 to 1.30 | -4.34 -9.08 to 0.92 | -4.68 -10.02 to 0.29 | -4.70 -11.09 to 1.26 |
| ORFO_PO_3MG_QD | -3.02 -6.44 to 0.90 | 6.11 1.19 to 10.66 | 4.14 -0.98 to 8.85 | 2.89 -0.85 to 6.59 | 2.31 -2.57 to 7.06 | 1.07 -2.77 to 4.91 | ORFO_PO_3MG_QD | -2.45 -9.00 to 3.36 | -2.75 -9.29 to 3.06 | -2.81 -7.78 to 2.40 | -3.28 -8.07 to 1.95 | -3.60 -9.16 to 1.45 | -3.62 -10.25 to 2.48 |
| METFORMIN | -0.55 -5.25 to 5.13 | 8.64 3.83 to 13.36 | 6.66 1.86 to 11.36 | 5.36 -0.83 to 11.68 | 4.82 0.21 to 9.40 | 3.56 -2.49 to 9.84 | 2.45 -3.36 to 9.00 | METFORMIN | -0.27 -3.89 to 3.31 | -0.31 -6.20 to 6.22 | -0.85 -6.66 to 6.08 | -1.13 -4.66 to 2.43 | -1.18 -6.23 to 3.84 |
| DULA_SC_1p5MG_QW | -0.27 -4.86 to 5.24 | 8.91 4.16 to 13.45 | 6.92 2.32 to 11.64 | 5.64 -0.49 to 11.98 | 5.09 0.54 to 9.90 | 3.82 -1.95 to 9.95 | 2.75 -3.06 to 9.29 | 0.27 -3.31 to 3.89 | DULA_SC_1p5MG_QW | 0.01 -5.80 to 6.27 | -0.50 -6.14 to 6.24 | -0.86 -4.36 to 2.77 | -0.91 -5.91 to 4.30 |
| ALBI_SC_50MG_QW | -0.22 -3.75 to 3.42 | 8.92 3.82 to 13.53 | 6.95 1.86 to 11.38 | 5.67 0.42 to 10.62 | 5.10 0.18 to 9.65 | 3.87 -1.30 to 8.70 | 2.81 -2.40 to 7.78 | 0.31 -6.22 to 6.20 | -0.01 -6.27 to 5.80 | ALBI_SC_50MG_QW | -0.47 -3.96 to 3.24 | -0.80 -6.35 to 4.14 | -0.86 -7.50 to 5.10 |
| ALBI_SC_30MG_QW | 0.26 -3.33 to 3.85 | 9.42 4.03 to 13.76 | 7.45 1.89 to 11.85 | 6.14 0.83 to 11.20 | 5.61 0.47 to 10.05 | 4.34 -0.92 to 9.08 | 3.28 -1.95 to 8.07 | 0.85 -6.08 to 6.66 | 0.50 -6.24 to 6.14 | 0.47 -3.24 to 3.96 | ALBI_SC_30MG_QW | -0.31 -6.31 to 4.51 | -0.36 -7.25 to 5.44 |
| DULA_SC_0p75MG_QW | 0.59 -2.85 to 4.93 | 9.76 6.41 to 12.83 | 7.75 4.47 to 11.01 | 6.50 1.36 to 11.97 | 5.94 2.71 to 9.20 | 4.68 -0.29 to 10.02 | 3.60 -1.45 to 9.16 | 1.13 -2.43 to 4.66 | 0.86 -2.77 to 4.36 | 0.80 -4.14 to 6.35 | 0.31 -4.51 to 6.31 | DULA_SC_0p75MG_QW | -0.05 -3.50 to 3.41 |
| LIRA_SC_0p9MG_QD | 0.64 -4.09 to 6.11 | 9.81 4.91 to 14.21 | 7.77 3.16 to 12.39 | 6.57 0.29 to 12.85 | 5.96 1.13 to 10.54 | 4.70 -1.26 to 11.09 | 3.62 -2.48 to 10.25 | 1.18 -3.84 to 6.23 | 0.91 -4.30 to 5.91 | 0.86 -5.10 to 7.50 | 0.36 -5.44 to 7.25 | 0.05 -3.41 to 3.50 | LIRA_SC_0p9MG_QD |
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?
| Comparison | Trials | Direct | Indirect | Network | P |
|---|---|---|---|---|---|
| Dulaglutide 0.75 mg subcutaneous once weekly versus Tirzepatide 10 mg subcutaneous once weekly DULA_SC_0p75MG_QW:TIRZ_SC_10MG_QW | 1 | 8.00 5.77 to 10.23 | 6.58 1.32 to 11.85 | 7.78 5.73 to 9.84 | 0.627 |
| Dulaglutide 0.75 mg subcutaneous once weekly versus Tirzepatide 15 mg subcutaneous once weekly DULA_SC_0p75MG_QW:TIRZ_SC_15MG_QW | 1 | 10.20 7.97 to 12.43 | 7.29 2.01 to 12.57 | 9.76 7.70 to 11.82 | 0.320 |
| Dulaglutide 0.75 mg subcutaneous once weekly versus Tirzepatide 5 mg subcutaneous once weekly DULA_SC_0p75MG_QW:TIRZ_SC_5MG_QW | 1 | 5.30 3.07 to 7.53 | 9.60 4.34 to 14.85 | 5.96 3.90 to 8.01 | 0.140 |
| Tirzepatide 10 mg subcutaneous once weekly versus Placebo TIRZ_SC_10MG_QW:PLACEBO | 1 | -7.10 -9.57 to -4.63 | -8.56 -13.90 to -3.22 | -7.36 -9.60 to -5.12 | 0.627 |
| Tirzepatide 15 mg subcutaneous once weekly versus Placebo TIRZ_SC_15MG_QW:PLACEBO | 1 | -8.80 -11.28 to -6.32 | -11.77 -17.07 to -6.46 | -9.33 -11.57 to -7.09 | 0.320 |
| Tirzepatide 5 mg subcutaneous once weekly versus Placebo TIRZ_SC_5MG_QW:PLACEBO | 1 | -6.30 -8.76 to -3.84 | -1.85 -7.23 to 3.53 | -5.53 -7.77 to -3.29 | 0.140 |
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.
Contribution of direct evidence
Percent contribution of each direct comparison (columns) to each network estimate (rows), from netcontrib.
| Network estimate | ALBI_SC_30MG_QW:ALBI_SC_50MG_QW:PLACEBO | DULA_SC_0p75MG_QW:DULA_SC_1p5MG_QW:METFORMIN | DULA_SC_0p75MG_QW:LIRA_SC_0p9MG_QD | DULA_SC_0p75MG_QW:TIRZ_SC_10MG_QW:TIRZ_SC_15MG_QW:TIRZ_SC_5MG_QW | ORFO_PO_12MG_QD:ORFO_PO_36MG_QD:ORFO_PO_3MG_QD:PLACEBO | PLACEBO:TIRZ_SC_10MG_QW:TIRZ_SC_15MG_QW:TIRZ_SC_5MG_QW |
|---|---|---|---|---|---|---|
| ALBI_SC_30MG_QW:PLACEBO | 100 | |||||
| ALBI_SC_50MG_QW:PLACEBO | 100 | |||||
| DULA_SC_0p75MG_QW:PLACEBO | 50 | 50 | ||||
| DULA_SC_1p5MG_QW:PLACEBO | 39 | 31 | 31 | |||
| LIRA_SC_0p9MG_QD:PLACEBO | 33 | 33 | 33 | |||
| METFORMIN:PLACEBO | 39 | 31 | 31 | |||
| ORFO_PO_12MG_QD:PLACEBO | 100 | |||||
| ORFO_PO_36MG_QD:PLACEBO | 100 | |||||
| ORFO_PO_3MG_QD:PLACEBO | 100 | |||||
| PLACEBO:TIRZ_SC_10MG_QW | 20 | 80 | ||||
| PLACEBO:TIRZ_SC_15MG_QW | 20 | 80 | ||||
| PLACEBO:TIRZ_SC_5MG_QW | 20 | 80 |
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 | Baseline BMI or body weight (kg/m2) effect modifier, prognostic factor; 5 of 6 | Sex (percent female) effect modifier, prognostic factor; 6 of 6 | Background glucose lowering therapy (stratum S0 to S4) effect modifier, prognostic factor; 6 of 6 | Asian ancestry or region (percent Asian) effect modifier, prognostic factor; 6 of 6 | Kidney function (eGFR) (mL/min/1.73 m2) prognostic factor, effect modifier; 3 of 6 | Treatment duration (weeks) effect modifier; 6 of 6 | Lifestyle co-intervention intensity (none standard intensive) effect modifier, prognostic factor; 6 of 6 |
|---|---|---|---|---|---|---|---|
| SURPASS J-mono S000239 | 28.13 | 24.49 | S0 | 100 | 78.12 | 52 | none |
| SURPASS-1 S000407 | 31.9 | 48.31 | S0 | 35.15 | 94.1 | 40 | not_reported |
| NCT01558271 S000837 | 25.51 | 19 | S0 | 98.98 | 72.35 median | 52 | not_reported |
| NCT00849017 S000852 | 33.53 | 44.88 100 minus male share | S0 | 2.36 | not reported | 156 | standard |
| NCT01126580 S001786 | 33.26 | 56.26 | S0 | 7.56 | eGFR below 60: 3.7 percent | 52 | not_reported |
| ACHIEVE-1 S001950 | body weight 90.2 kg | 48.12 | S0 | 43.83 | not reported | 40 | 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 25.5 (DULA_SC_0p75MG_QW vs LIRA_SC_0p9MG_QD) to 33.5 (ALBI_SC_30MG_QW vs ALBI_SC_50MG_QW vs PLACEBO) kg/m2; threshold 3
- FlagBaseline, Sex: design means range from 19.0 (DULA_SC_0p75MG_QW vs LIRA_SC_0p9MG_QD) to 56.3 (DULA_SC_0p75MG_QW vs DULA_SC_1p5MG_QW vs METFORMIN) percent female; threshold 15
- FlagBaseline, Asian ancestry or region: design means range from 2.4 (ALBI_SC_30MG_QW vs ALBI_SC_50MG_QW vs PLACEBO) to 100.0 (DULA_SC_0p75MG_QW vs TIRZ_SC_10MG_QW vs TIRZ_SC_15MG_QW vs TIRZ_SC_5MG_QW) percent Asian; threshold 30
- FlagBaseline, Kidney function (eGFR): not reported by 3 of 6 trials
- FlagBaseline, Kidney function (eGFR): design means range from 72.3 (DULA_SC_0p75MG_QW vs LIRA_SC_0p9MG_QD) to 94.1 (PLACEBO vs TIRZ_SC_10MG_QW vs TIRZ_SC_15MG_QW vs TIRZ_SC_5MG_QW) mL/min/1.73 m2; threshold 15
- FlagBaseline, Treatment duration: design means range from 40.0 (ORFO_PO_12MG_QD vs ORFO_PO_36MG_QD vs ORFO_PO_3MG_QD vs PLACEBO) to 156.0 (ALBI_SC_30MG_QW vs ALBI_SC_50MG_QW vs PLACEBO) weeks; threshold 26
- NoteOutcome assessment, time point: selected time points span 40 to 52 weeks
- NoteOutcome assessment, intercurrent events (discontinuation): mixed: hypothetical 4, not stated 2
- NoteOutcome assessment, intercurrent events (rescue): mixed: hypothetical 4, not stated 2
| Trial | time weeks | analysis set | definition | instrument | adjudicated | proportion method | intercurrent events (discontinuation) | intercurrent events (rescue) | blinding | funding | start year | Eligibility |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SURPASS J-mono | 52 | modified_itt | not stated | not stated | not stated | not stated | hypothetical | hypothetical | double_blind | industry | 2019 | Japanese adults 20 or older; BMI 23 or more; HbA1c 7.0 to 10.0 percent; drug naive or oral monotherapy washed out |
| SURPASS-1 | 40 | modified_itt | not stated | not stated | not stated | not stated | hypothetical | hypothetical | double_blind | industry | 2019 | adults; HbA1c 7.0 to 9.5 percent; BMI 23 or higher; no glucose lowering drug in prior 90 days |
| NCT01558271 | 52 | modified_itt | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2012 | Japanese; age 20 or more; BMI 18.5 to 35; HbA1c 7.0 to 10.0 percent; OAM naive or OAM stopped |
| NCT00849017 | 52 | modified_itt | not stated | not stated | not stated | not stated | hypothetical | hypothetical | double_blind | industry | 2009 | age 18 or older; HbA1c 7.0 to 10.0 percent; BMI 20 to 45; diet and exercise only |
| NCT01126580 | 52 | modified_itt | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2010 | type 2 diabetes on diet and exercise or one oral drug; registry gives no ranges |
| ACHIEVE-1 | 40 | modified_itt | not stated | not stated | not stated | not stated | hypothetical | hypothetical | double_blind | industry | 2023 | adults with type 2 diabetes on diet and exercise alone; HbA1c 7.0 to 9.5 percent |
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 |
|---|---|---|---|---|---|---|---|---|---|
| SURPASS J-mono | A1 | TIRZ_SC_5MG_QW | 52 | arm, change | -5.800 | 0.400 | 143 | R0012580:Table 2 | |
| SURPASS J-mono | A2 | TIRZ_SC_10MG_QW | 52 | arm, change | -8.500 | 0.400 | 135 | R0012580:Table 2 | |
| SURPASS J-mono | A3 | TIRZ_SC_15MG_QW | 52 | arm, change | -10.700 | 0.400 | 134 | R0012580:Table 2 | |
| SURPASS J-mono | A4 | DULA_SC_0p75MG_QW | 52 | arm, change | -0.500 | 0.400 | 138 | R0012580:Table 2 | |
| SURPASS-1 | A1 | TIRZ_SC_5MG_QW | 40 | arm, change | -7.000 | 0.520 | 121 | registry:outcomes | |
| SURPASS-1 | A2 | TIRZ_SC_10MG_QW | 40 | arm, change | -7.800 | 0.530 | 118 | registry:outcomes | |
| SURPASS-1 | A3 | TIRZ_SC_15MG_QW | 40 | arm, change | -9.500 | 0.540 | 116 | registry:outcomes | |
| SURPASS-1 | A4 | PLACEBO | 40 | arm, change | -0.700 | 0.570 | 112 | registry:outcomes | |
| NCT01558271 | A1 | DULA_SC_0p75MG_QW | 52 | arm, change | -0.170 | 0.180 | 280 | registry:outcomes | |
| NCT01558271 | A2 | LIRA_SC_0p9MG_QD | 52 | arm, change | -0.130 | 0.260 | 136 | registry:outcomes | |
| NCT00849017 | A1 | PLACEBO | 52 | arm, change | -0.660 | 0.428 | 99 | registry:outcomes | |
| NCT00849017 | A2 | ALBI_SC_30MG_QW | 52 | arm, change | -0.390 | 0.424 | 100 | registry:outcomes | |
| NCT00849017 | A3 | ALBI_SC_50MG_QW | 52 | arm, change | -0.860 | 0.432 | 97 | registry:outcomes | |
| NCT01126580 | A1 | DULA_SC_1p5MG_QW | 52 | arm, change | -1.930 | 0.290 | 267 | registry:outcomes | |
| NCT01126580 | A2 | DULA_SC_0p75MG_QW | 52 | arm, change | -1.090 | 0.290 | 269 | registry:outcomes | |
| NCT01126580 | A3 | METFORMIN | 52 | arm, change | -2.200 | 0.290 | 267 | registry:outcomes | |
| ACHIEVE-1 | A1 | PLACEBO | 40 | arm, change | -1.300 | 0.360 | 138 | registry:outcomes | |
| ACHIEVE-1 | A2 | ORFO_PO_3MG_QD | 40 | arm, change | -4.400 | 0.430 | 143 | registry:outcomes | |
| ACHIEVE-1 | A3 | ORFO_PO_12MG_QD | 40 | arm, change | -5.500 | 0.490 | 137 | registry:outcomes | |
| ACHIEVE-1 | A4 | ORFO_PO_36MG_QD | 40 | arm, change | -7.300 | 0.550 | 141 | registry:outcomes |
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.