Percent body weight change
Overweight or obesity without diabetes (adults)
In plain language
Across 13 trials with 2,153 participants, 11 of 22 treatments had a clearly better result than placebo on percent body weight change, and for 11 the evidence could not tell them apart from placebo. The most favorable estimate was for Bofanglutide 48 mg injection every 2 weeks: mean difference -15.10 percentage points (95% credible interval -21.91 to -6.09).
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 |
|---|---|---|---|---|
| Bofanglutide 48 mg injection every 2 weeks BOFANG_SC_48MG_Q2W | -15.10 (-21.91 to -6.09) | -25.26 to -3.04 | -16.64 (-24.49 to -8.79) | Better |
| Mazdutide 16 mg injection once weekly MAZD_SC_16MG_QW | -14.60 (-22.59 to -5.62) | -25.69 to -1.95 | -15.30 (-23.59 to -7.01) | Better |
| Bofanglutide 24 mg injection once weekly BOFANG_SC_24MG_QW | -13.78 (-20.74 to -4.67) | -23.85 to -1.18 | -15.35 (-23.23 to -7.47) | Better |
| Mazdutide 6 mg subcutaneous once weekly MAZD_SC_6MG_QW | -11.44 (-18.85 to -2.90) | -22.38 to 0.07 | -12.30 (-20.04 to -4.56) | Better |
| Bofanglutide 24 mg injection every 2 weeks BOFANG_SC_24MG_Q2W | -10.90 (-17.87 to -1.86) | -21.45 to 1.62 | -12.41 (-20.29 to -4.53) | Better |
| Mazdutide 4.5 mg subcutaneous once weekly MAZD_SC_4p5MG_QW | -10.53 (-17.85 to -2.01) | -20.95 to 1.36 | -11.40 (-19.14 to -3.66) | Better |
| Bofanglutide 18 mg injection every 2 weeks BOFANG_SC_18MG_Q2W | -10.05 (-17.07 to -1.32) | -20.37 to 2.33 | -11.57 (-19.45 to -3.69) | Better |
| Orforglipron 45 mg oral once daily ORFO_PO_45MG_QD | -9.69 (-16.67 to -1.16) | -20.07 to 2.34 | -10.60 (-18.40 to -2.80) | Better |
| Orforglipron 36 mg oral once daily ORFO_PO_36MG_QD | -9.39 (-16.57 to -0.67) | -20.05 to 2.59 | -10.30 (-18.10 to -2.50) | Better |
| Semaglutide 2.4 mg subcutaneous once weekly SEMA_SC_2p4MG_QW | -8.68 (-14.57 to -2.79) | -18.83 to 1.43 | -9.03 (-14.72 to -3.33) | Better |
| Orforglipron 24 mg oral once daily ORFO_PO_24MG_QD | -8.23 (-15.32 to 0.19) | -18.59 to 3.72 | -9.20 (-17.02 to -1.38) | Unclear |
| Bofanglutide 12 mg injection every 2 weeks BOFANG_SC_12MG_Q2W | -7.40 (-14.36 to 1.64) | -17.92 to 5.09 | -8.79 (-16.67 to -0.91) | Unclear |
| Mazdutide 3 mg subcutaneous once weekly MAZD_SC_3MG_QW | -6.93 (-14.24 to 1.52) | -17.69 to 5.01 | -7.70 (-15.44 to 0.04) | Unclear |
| Efpeglenatide 8 mg injection every 2 weeks EFPE_SC_8MG_Q2W | -6.81 (-14.06 to 1.88) | -17.53 to 4.76 | -7.50 (-15.17 to 0.17) | Unclear |
| Efpeglenatide 6 mg subcutaneous once weekly EFPE_SC_6MG_QW | -6.76 (-13.91 to 1.73) | -17.57 to 4.70 | -7.40 (-15.07 to 0.27) | Unclear |
| Efpeglenatide 6 mg injection every 2 weeks EFPE_SC_6MG_Q2W | -6.19 (-13.27 to 2.36) | -16.63 to 5.89 | -6.80 (-14.47 to 0.87) | Unclear |
| Efpeglenatide 4 mg subcutaneous once weekly EFPE_SC_4MG_QW | -6.10 (-13.37 to 2.01) | -16.83 to 5.44 | -6.80 (-14.47 to 0.87) | Unclear |
| Orforglipron 12 mg oral once daily ORFO_PO_12MG_QD | -5.70 (-13.11 to 3.01) | -16.04 to 6.16 | -6.60 (-14.44 to 1.24) | Unclear |
| Liraglutide 3.0 mg subcutaneous once daily LIRA_SC_3p0MG_QD | -5.11 (-9.87 to -0.40) | -14.46 to 4.05 | -5.22 (-9.68 to -0.76) | Better |
| Exenatide extended release and dapagliflozin 2 to 10 mg injection once weekly EXENER_SC_2-10MG_QW | -4.11 (-11.89 to 4.07) | -15.28 to 7.21 | -4.20 (-12.03 to 3.63) | Unclear |
| Exenatide 10 ug subcutaneous twice daily EXEN_SC_10UG_BID | -3.13 (-10.82 to 4.73) | -14.25 to 8.07 | -3.30 (-10.85 to 4.25) | Unclear |
| Standard care or no added treatment STANDARD_CARE | -0.66 (-9.85 to 8.19) | -12.58 to 11.11 | -0.80 (-9.64 to 8.05) | Unclear |
Ranking
League table
| Row versus column | PLACEBO | BOFANG_SC_48MG_Q2W | MAZD_SC_16MG_QW | BOFANG_SC_24MG_QW | MAZD_SC_6MG_QW | BOFANG_SC_24MG_Q2W | MAZD_SC_4p5MG_QW | BOFANG_SC_18MG_Q2W | ORFO_PO_45MG_QD | ORFO_PO_36MG_QD | SEMA_SC_2p4MG_QW | ORFO_PO_24MG_QD | BOFANG_SC_12MG_Q2W | MAZD_SC_3MG_QW | EFPE_SC_8MG_Q2W | EFPE_SC_6MG_QW | EFPE_SC_6MG_Q2W | EFPE_SC_4MG_QW | ORFO_PO_12MG_QD | LIRA_SC_3p0MG_QD | EXENER_SC_2-10MG_QW | EXEN_SC_10UG_BID | STANDARD_CARE |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PLACEBO | PLACEBO | 15.10 6.09 to 21.91 | 14.60 5.62 to 22.59 | 13.78 4.67 to 20.74 | 11.44 2.90 to 18.85 | 10.90 1.86 to 17.87 | 10.53 2.01 to 17.85 | 10.05 1.32 to 17.07 | 9.69 1.16 to 16.67 | 9.39 0.67 to 16.57 | 8.68 2.79 to 14.57 | 8.23 -0.19 to 15.32 | 7.40 -1.64 to 14.36 | 6.93 -1.52 to 14.24 | 6.81 -1.88 to 14.06 | 6.76 -1.73 to 13.91 | 6.19 -2.36 to 13.27 | 6.10 -2.01 to 13.37 | 5.70 -3.01 to 13.11 | 5.11 0.40 to 9.87 | 4.11 -4.07 to 11.89 | 3.13 -4.73 to 10.82 | 0.66 -8.19 to 9.85 |
| BOFANG_SC_48MG_Q2W | -15.10 -21.91 to -6.09 | BOFANG_SC_48MG_Q2W | -0.47 -11.47 to 11.32 | -1.34 -9.70 to 7.30 | -3.58 -14.02 to 7.90 | -4.14 -11.90 to 3.76 | -4.50 -15.29 to 6.90 | -5.00 -12.99 to 3.31 | -5.45 -16.05 to 5.88 | -5.65 -16.22 to 5.63 | -6.37 -15.21 to 4.72 | -6.91 -17.52 to 4.38 | -7.72 -15.84 to 0.67 | -8.15 -18.59 to 3.30 | -8.18 -18.77 to 2.76 | -8.28 -18.80 to 3.15 | -8.97 -19.43 to 2.47 | -9.00 -19.23 to 2.21 | -9.41 -19.62 to 2.39 | -9.92 -17.88 to 0.10 | -10.99 -21.19 to 1.08 | -11.95 -22.20 to 0.17 | -14.45 -25.10 to -1.46 |
| MAZD_SC_16MG_QW | -14.60 -22.59 to -5.62 | 0.47 -11.32 to 11.47 | MAZD_SC_16MG_QW | -0.91 -12.84 to 9.94 | -3.16 -14.69 to 8.37 | -3.74 -15.40 to 7.65 | -4.13 -15.53 to 7.78 | -4.58 -16.93 to 6.36 | -4.97 -16.57 to 6.39 | -5.17 -17.19 to 5.98 | -6.04 -15.65 to 5.04 | -6.41 -18.06 to 4.89 | -7.26 -18.66 to 4.08 | -7.64 -19.06 to 3.75 | -7.80 -19.13 to 3.87 | -7.88 -19.10 to 3.54 | -8.48 -20.21 to 3.02 | -8.54 -19.60 to 2.72 | -8.90 -20.55 to 2.50 | -9.41 -18.76 to 0.78 | -10.55 -21.49 to 1.29 | -11.49 -22.54 to 0.55 | -13.95 -25.77 to -1.03 |
| BOFANG_SC_24MG_QW | -13.78 -20.74 to -4.67 | 1.34 -7.30 to 9.70 | 0.91 -9.94 to 12.84 | BOFANG_SC_24MG_QW | -2.29 -13.37 to 9.39 | -2.77 -11.30 to 5.45 | -3.23 -14.21 to 8.72 | -3.66 -12.13 to 4.99 | -4.10 -14.85 to 7.41 | -4.28 -15.12 to 6.85 | -5.07 -13.88 to 5.82 | -5.55 -16.25 to 6.17 | -6.42 -14.62 to 2.49 | -6.86 -17.40 to 4.96 | -6.86 -17.69 to 4.62 | -6.99 -17.83 to 4.56 | -7.61 -18.32 to 3.73 | -7.63 -17.96 to 4.19 | -8.09 -18.72 to 4.02 | -8.72 -16.75 to 1.70 | -9.70 -20.01 to 2.70 | -10.65 -21.07 to 1.62 | -13.07 -23.98 to 0.16 |
| MAZD_SC_6MG_QW | -11.44 -18.85 to -2.90 | 3.58 -7.90 to 14.02 | 3.16 -8.37 to 14.69 | 2.29 -9.39 to 13.37 | MAZD_SC_6MG_QW | -0.53 -11.90 to 9.97 | -0.93 -9.23 to 7.17 | -1.37 -13.07 to 9.23 | -1.78 -13.14 to 8.86 | -2.12 -13.19 to 9.04 | -2.84 -11.97 to 7.48 | -3.19 -14.62 to 7.64 | -4.10 -15.32 to 6.71 | -4.52 -12.70 to 3.42 | -4.59 -16.15 to 6.52 | -4.73 -15.86 to 6.34 | -5.29 -16.66 to 5.84 | -5.38 -16.48 to 6.01 | -5.78 -16.64 to 5.10 | -6.39 -15.03 to 3.52 | -7.38 -18.29 to 4.13 | -8.29 -19.10 to 2.99 | -10.81 -21.73 to 1.84 |
| BOFANG_SC_24MG_Q2W | -10.90 -17.87 to -1.86 | 4.14 -3.76 to 11.90 | 3.74 -7.65 to 15.40 | 2.77 -5.45 to 11.30 | 0.53 -9.97 to 11.90 | BOFANG_SC_24MG_Q2W | -0.37 -10.85 to 11.10 | -0.91 -8.99 to 7.34 | -1.28 -12.13 to 10.13 | -1.62 -12.28 to 9.84 | -2.22 -11.63 to 8.78 | -2.76 -13.35 to 8.43 | -3.58 -11.81 to 4.99 | -4.04 -14.45 to 7.12 | -4.09 -14.89 to 7.40 | -4.06 -14.88 to 7.23 | -4.73 -15.55 to 6.57 | -4.80 -15.13 to 6.40 | -5.22 -15.85 to 6.68 | -5.80 -14.18 to 4.43 | -6.85 -16.94 to 5.20 | -7.81 -18.00 to 4.05 | -10.20 -21.20 to 2.99 |
| MAZD_SC_4p5MG_QW | -10.53 -17.85 to -2.01 | 4.50 -6.90 to 15.29 | 4.13 -7.78 to 15.53 | 3.23 -8.72 to 14.21 | 0.93 -7.17 to 9.23 | 0.37 -11.10 to 10.85 | MAZD_SC_4p5MG_QW | -0.51 -12.26 to 10.23 | -0.86 -12.04 to 10.29 | -1.18 -12.10 to 9.50 | -1.93 -11.06 to 8.61 | -2.32 -13.57 to 8.76 | -3.14 -14.57 to 7.66 | -3.64 -11.66 to 4.39 | -3.66 -14.95 to 7.56 | -3.81 -15.01 to 7.30 | -4.40 -15.84 to 7.10 | -4.40 -15.67 to 6.78 | -4.78 -15.94 to 6.11 | -5.46 -14.20 to 4.48 | -6.41 -17.32 to 5.00 | -7.41 -18.32 to 4.17 | -9.90 -21.24 to 2.80 |
| BOFANG_SC_18MG_Q2W | -10.05 -17.07 to -1.32 | 5.00 -3.31 to 12.99 | 4.58 -6.36 to 16.93 | 3.66 -4.99 to 12.13 | 1.37 -9.23 to 13.07 | 0.91 -7.34 to 8.99 | 0.51 -10.23 to 12.26 | BOFANG_SC_18MG_Q2W | -0.47 -11.30 to 11.38 | -0.62 -11.67 to 10.50 | -1.46 -10.55 to 9.59 | -1.89 -12.53 to 9.32 | -2.69 -11.02 to 5.99 | -3.15 -13.61 to 8.31 | -3.25 -13.88 to 8.26 | -3.33 -13.93 to 8.18 | -3.98 -14.80 to 7.30 | -3.99 -14.38 to 7.56 | -4.43 -15.23 to 7.30 | -4.93 -13.18 to 5.04 | -6.05 -16.54 to 6.20 | -6.94 -17.21 to 5.19 | -9.36 -20.64 to 3.75 |
| ORFO_PO_45MG_QD | -9.69 -16.67 to -1.16 | 5.45 -5.88 to 16.05 | 4.97 -6.39 to 16.57 | 4.10 -7.41 to 14.85 | 1.78 -8.86 to 13.14 | 1.28 -10.13 to 12.13 | 0.86 -10.29 to 12.04 | 0.47 -11.38 to 11.30 | ORFO_PO_45MG_QD | -0.30 -8.55 to 7.86 | -1.01 -9.84 to 9.67 | -1.40 -9.37 to 6.59 | -2.24 -13.54 to 8.63 | -2.73 -13.51 to 8.43 | -2.80 -13.68 to 8.27 | -2.94 -13.70 to 8.55 | -3.53 -14.29 to 7.76 | -3.53 -14.02 to 7.93 | -3.94 -11.89 to 4.18 | -4.54 -13.25 to 5.72 | -5.63 -16.18 to 5.91 | -6.50 -17.06 to 4.79 | -9.00 -20.19 to 3.82 |
| ORFO_PO_36MG_QD | -9.39 -16.57 to -0.67 | 5.65 -5.63 to 16.22 | 5.17 -5.98 to 17.19 | 4.28 -6.85 to 15.12 | 2.12 -9.04 to 13.19 | 1.62 -9.84 to 12.28 | 1.18 -9.50 to 12.10 | 0.62 -10.50 to 11.67 | 0.30 -7.86 to 8.55 | ORFO_PO_36MG_QD | -0.74 -9.92 to 9.95 | -1.16 -9.21 to 7.03 | -2.00 -13.18 to 8.81 | -2.57 -13.12 to 8.66 | -2.53 -13.54 to 8.65 | -2.52 -13.43 to 8.58 | -3.32 -14.67 to 8.15 | -3.26 -14.16 to 8.14 | -3.65 -11.72 to 4.96 | -4.24 -12.94 to 5.92 | -5.27 -16.09 to 6.58 | -6.32 -17.04 to 5.46 | -8.71 -19.91 to 3.84 |
| SEMA_SC_2p4MG_QW | -8.68 -14.57 to -2.79 | 6.37 -4.72 to 15.21 | 6.04 -5.04 to 15.65 | 5.07 -5.82 to 13.88 | 2.84 -7.48 to 11.97 | 2.22 -8.78 to 11.63 | 1.93 -8.61 to 11.06 | 1.46 -9.59 to 10.55 | 1.01 -9.67 to 9.84 | 0.74 -9.95 to 9.92 | SEMA_SC_2p4MG_QW | -0.44 -11.02 to 8.61 | -1.33 -12.06 to 7.67 | -1.71 -12.43 to 7.25 | -1.86 -11.91 to 7.16 | -1.91 -12.25 to 7.19 | -2.54 -12.97 to 6.45 | -2.55 -12.51 to 6.58 | -2.99 -13.45 to 6.28 | -3.55 -11.12 to 4.03 | -4.55 -14.89 to 5.00 | -5.50 -15.34 to 4.24 | -7.94 -18.57 to 2.84 |
| ORFO_PO_24MG_QD | -8.23 -15.32 to 0.19 | 6.91 -4.38 to 17.52 | 6.41 -4.89 to 18.06 | 5.55 -6.17 to 16.25 | 3.19 -7.64 to 14.62 | 2.76 -8.43 to 13.35 | 2.32 -8.76 to 13.57 | 1.89 -9.32 to 12.53 | 1.40 -6.59 to 9.37 | 1.16 -7.03 to 9.21 | 0.44 -8.61 to 11.02 | ORFO_PO_24MG_QD | -0.84 -12.16 to 9.65 | -1.33 -11.72 to 9.69 | -1.43 -12.22 to 9.80 | -1.46 -12.21 to 9.41 | -2.09 -12.95 to 8.69 | -2.12 -12.86 to 9.06 | -2.49 -10.63 to 5.41 | -3.16 -11.55 to 6.86 | -4.15 -14.76 to 7.00 | -5.10 -15.40 to 6.26 | -7.57 -18.46 to 5.10 |
| BOFANG_SC_12MG_Q2W | -7.40 -14.36 to 1.64 | 7.72 -0.67 to 15.84 | 7.26 -4.08 to 18.66 | 6.42 -2.49 to 14.62 | 4.10 -6.71 to 15.32 | 3.58 -4.99 to 11.81 | 3.14 -7.66 to 14.57 | 2.69 -5.99 to 11.02 | 2.24 -8.63 to 13.54 | 2.00 -8.81 to 13.18 | 1.33 -7.67 to 12.06 | 0.84 -9.65 to 12.16 | BOFANG_SC_12MG_Q2W | -0.47 -11.02 to 10.61 | -0.48 -11.28 to 10.87 | -0.64 -11.52 to 10.88 | -1.24 -11.99 to 9.97 | -1.30 -11.84 to 10.38 | -1.79 -12.71 to 10.01 | -2.28 -10.51 to 7.95 | -3.37 -13.99 to 8.91 | -4.30 -14.54 to 7.93 | -6.78 -17.66 to 6.61 |
| MAZD_SC_3MG_QW | -6.93 -14.24 to 1.52 | 8.15 -3.30 to 18.59 | 7.64 -3.75 to 19.06 | 6.86 -4.96 to 17.40 | 4.52 -3.42 to 12.70 | 4.04 -7.12 to 14.45 | 3.64 -4.39 to 11.66 | 3.15 -8.31 to 13.61 | 2.73 -8.43 to 13.51 | 2.57 -8.66 to 13.12 | 1.71 -7.25 to 12.43 | 1.33 -9.69 to 11.72 | 0.47 -10.61 to 11.02 | MAZD_SC_3MG_QW | -0.00 -10.77 to 10.93 | -0.18 -11.28 to 10.87 | -0.73 -11.62 to 10.16 | -0.78 -11.82 to 10.08 | -1.19 -12.32 to 9.61 | -1.77 -10.16 to 7.86 | -2.80 -13.90 to 8.55 | -3.76 -14.32 to 7.82 | -6.16 -17.20 to 6.03 |
| EFPE_SC_8MG_Q2W | -6.81 -14.06 to 1.88 | 8.18 -2.76 to 18.77 | 7.80 -3.87 to 19.13 | 6.86 -4.62 to 17.69 | 4.59 -6.52 to 16.15 | 4.09 -7.40 to 14.89 | 3.66 -7.56 to 14.95 | 3.25 -8.26 to 13.88 | 2.80 -8.27 to 13.68 | 2.53 -8.65 to 13.54 | 1.86 -7.16 to 11.91 | 1.43 -9.80 to 12.22 | 0.48 -10.87 to 11.28 | 0.00 -10.93 to 10.77 | EFPE_SC_8MG_Q2W | -0.13 -7.79 to 7.72 | -0.78 -8.40 to 7.25 | -0.79 -8.52 to 7.50 | -1.12 -12.19 to 9.94 | -1.76 -10.30 to 8.02 | -2.82 -13.59 to 9.25 | -3.74 -14.06 to 7.74 | -6.14 -17.56 to 6.72 |
| EFPE_SC_6MG_QW | -6.76 -13.91 to 1.73 | 8.28 -3.15 to 18.80 | 7.88 -3.54 to 19.10 | 6.99 -4.56 to 17.83 | 4.73 -6.34 to 15.86 | 4.06 -7.23 to 14.88 | 3.81 -7.30 to 15.01 | 3.33 -8.18 to 13.93 | 2.94 -8.55 to 13.70 | 2.52 -8.58 to 13.43 | 1.91 -7.19 to 12.25 | 1.46 -9.41 to 12.21 | 0.64 -10.88 to 11.52 | 0.18 -10.87 to 11.28 | 0.13 -7.72 to 7.79 | EFPE_SC_6MG_QW | -0.64 -8.83 to 7.18 | -0.63 -8.52 to 7.16 | -1.06 -12.17 to 10.05 | -1.60 -10.11 to 8.09 | -2.74 -13.51 to 9.16 | -3.66 -13.86 to 7.76 | -6.06 -17.46 to 6.48 |
| EFPE_SC_6MG_Q2W | -6.19 -13.27 to 2.36 | 8.97 -2.47 to 19.43 | 8.48 -3.02 to 20.21 | 7.61 -3.73 to 18.32 | 5.29 -5.84 to 16.66 | 4.73 -6.57 to 15.55 | 4.40 -7.10 to 15.84 | 3.98 -7.30 to 14.80 | 3.53 -7.76 to 14.29 | 3.32 -8.15 to 14.67 | 2.54 -6.45 to 12.97 | 2.09 -8.69 to 12.95 | 1.24 -9.97 to 11.99 | 0.73 -10.16 to 11.62 | 0.78 -7.25 to 8.40 | 0.64 -7.18 to 8.83 | EFPE_SC_6MG_Q2W | 0.03 -7.96 to 8.14 | -0.39 -11.64 to 10.51 | -1.05 -9.14 to 8.69 | -2.09 -13.13 to 10.03 | -3.00 -13.20 to 8.60 | -5.45 -16.70 to 7.23 |
| EFPE_SC_4MG_QW | -6.10 -13.37 to 2.01 | 9.00 -2.21 to 19.23 | 8.54 -2.72 to 19.60 | 7.63 -4.19 to 17.96 | 5.38 -6.01 to 16.48 | 4.80 -6.40 to 15.13 | 4.40 -6.78 to 15.67 | 3.99 -7.56 to 14.38 | 3.53 -7.93 to 14.02 | 3.26 -8.14 to 14.16 | 2.55 -6.58 to 12.51 | 2.12 -9.06 to 12.86 | 1.30 -10.38 to 11.84 | 0.78 -10.08 to 11.82 | 0.79 -7.50 to 8.52 | 0.63 -7.16 to 8.52 | -0.03 -8.14 to 7.96 | EFPE_SC_4MG_QW | -0.40 -11.81 to 10.49 | -1.04 -9.43 to 8.69 | -2.03 -12.70 to 9.42 | -3.02 -13.16 to 8.39 | -5.41 -16.60 to 6.93 |
| ORFO_PO_12MG_QD | -5.70 -13.11 to 3.01 | 9.41 -2.39 to 19.62 | 8.90 -2.50 to 20.55 | 8.09 -4.02 to 18.72 | 5.78 -5.10 to 16.64 | 5.22 -6.68 to 15.85 | 4.78 -6.11 to 15.94 | 4.43 -7.30 to 15.23 | 3.94 -4.18 to 11.89 | 3.65 -4.96 to 11.72 | 2.99 -6.28 to 13.45 | 2.49 -5.41 to 10.63 | 1.79 -10.01 to 12.71 | 1.19 -9.61 to 12.32 | 1.12 -9.94 to 12.19 | 1.06 -10.05 to 12.17 | 0.39 -10.51 to 11.64 | 0.40 -10.49 to 11.81 | ORFO_PO_12MG_QD | -0.54 -9.33 to 9.36 | -1.55 -12.57 to 10.04 | -2.51 -13.43 to 9.13 | -4.98 -16.27 to 7.50 |
| LIRA_SC_3p0MG_QD | -5.11 -9.87 to -0.40 | 9.92 -0.10 to 17.88 | 9.41 -0.78 to 18.76 | 8.72 -1.70 to 16.75 | 6.39 -3.52 to 15.03 | 5.80 -4.43 to 14.18 | 5.46 -4.48 to 14.20 | 4.93 -5.04 to 13.18 | 4.54 -5.72 to 13.25 | 4.24 -5.92 to 12.94 | 3.55 -4.03 to 11.12 | 3.16 -6.86 to 11.55 | 2.28 -7.95 to 10.51 | 1.77 -7.86 to 10.16 | 1.76 -8.02 to 10.30 | 1.60 -8.09 to 10.11 | 1.05 -8.69 to 9.14 | 1.04 -8.69 to 9.43 | 0.54 -9.36 to 9.33 | LIRA_SC_3p0MG_QD | -1.06 -10.69 to 8.40 | -2.01 -11.32 to 7.07 | -4.46 -12.05 to 3.44 |
| EXENER_SC_2-10MG_QW | -4.11 -11.89 to 4.07 | 10.99 -1.08 to 21.19 | 10.55 -1.29 to 21.49 | 9.70 -2.70 to 20.01 | 7.38 -4.13 to 18.29 | 6.85 -5.20 to 16.94 | 6.41 -5.00 to 17.32 | 6.05 -6.20 to 16.54 | 5.63 -5.91 to 16.18 | 5.27 -6.58 to 16.09 | 4.55 -5.00 to 14.89 | 4.15 -7.00 to 14.76 | 3.37 -8.91 to 13.99 | 2.80 -8.55 to 13.90 | 2.82 -9.25 to 13.59 | 2.74 -9.16 to 13.51 | 2.09 -10.03 to 13.13 | 2.03 -9.42 to 12.70 | 1.55 -10.04 to 12.57 | 1.06 -8.40 to 10.69 | EXENER_SC_2-10MG_QW | -0.97 -11.95 to 10.26 | -3.36 -15.43 to 8.97 |
| EXEN_SC_10UG_BID | -3.13 -10.82 to 4.73 | 11.95 -0.17 to 22.20 | 11.49 -0.55 to 22.54 | 10.65 -1.62 to 21.07 | 8.29 -2.99 to 19.10 | 7.81 -4.05 to 18.00 | 7.41 -4.17 to 18.32 | 6.94 -5.19 to 17.21 | 6.50 -4.79 to 17.06 | 6.32 -5.46 to 17.04 | 5.50 -4.24 to 15.34 | 5.10 -6.26 to 15.40 | 4.30 -7.93 to 14.54 | 3.76 -7.82 to 14.32 | 3.74 -7.74 to 14.06 | 3.66 -7.76 to 13.86 | 3.00 -8.60 to 13.20 | 3.02 -8.39 to 13.16 | 2.51 -9.13 to 13.43 | 2.01 -7.07 to 11.32 | 0.97 -10.26 to 11.95 | EXEN_SC_10UG_BID | -2.46 -14.00 to 9.44 |
| STANDARD_CARE | -0.66 -9.85 to 8.19 | 14.45 1.46 to 25.10 | 13.95 1.03 to 25.77 | 13.07 -0.16 to 23.98 | 10.81 -1.84 to 21.73 | 10.20 -2.99 to 21.20 | 9.90 -2.80 to 21.24 | 9.36 -3.75 to 20.64 | 9.00 -3.82 to 20.19 | 8.71 -3.84 to 19.91 | 7.94 -2.84 to 18.57 | 7.57 -5.10 to 18.46 | 6.78 -6.61 to 17.66 | 6.16 -6.03 to 17.20 | 6.14 -6.72 to 17.56 | 6.06 -6.48 to 17.46 | 5.45 -7.23 to 16.70 | 5.41 -6.93 to 16.60 | 4.98 -7.50 to 16.27 | 4.46 -3.44 to 12.05 | 3.36 -8.97 to 15.43 | 2.46 -9.44 to 14.00 | STANDARD_CARE |
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; 13 of 13 | Type 2 diabetes share in weight trials (percent of participants) effect modifier; 13 of 13 | Sex (percent female) effect modifier, prognostic factor; 13 of 13 | Asian ancestry or region (percent Asian) effect modifier, prognostic factor; 9 of 13 | Treatment duration (weeks) effect modifier; 13 of 13 | Lifestyle co-intervention intensity (none standard intensive) effect modifier, prognostic factor; 13 of 13 |
|---|---|---|---|---|---|---|
| BARI-STEP S000434 | 41.5 | 10 | 82.85 | 2.85 | 68 | standard |
| BARIOPTIMISE S000466 | 43.1 | 13 | 74 | 7.14 | 24 | standard |
| NCT00500370 S000663 | 39.51 | 0 population codes | 76.69 | not reported | 24 | intensive |
| NCT02075281 S000743 | 35.44 | 0 population codes | 76.35 | 8.49 | 20 | standard |
| NCT04904913 S001183 | 31.83 | 0 population codes | 52.03 | 100 | 24 | none |
| Dapalost S001235 | 35.4 | 0 population codes | 61.25 | not reported | 24 | standard |
| STABLE Wt Loss S001294 | 37.48 | 0 population codes | 78.36 | 4.2 | 60 | not_reported;standard |
| NCT05623839 S001559 | 32.5 | 0 population codes | 50 | not reported | 20 | none |
| STRIVE S001687 | 45.96 | 35.5 | 64.28 | 3.56 | 104 | intensive |
| NCT01557166 S002315 | 39.15 | 0 population codes | 28.1 | 4.46 | 32 | standard |
| NCT05051579 S002337 | 38.08 | 0 population codes | 59.19 | 0.74 | 36 | standard |
| NCT06256562 S002790 | 33.23 | 0 population codes | 45.62 | 100 | 30 | standard |
| S003017 S003017 | 38.05 | 0 population codes | 87.5 | not reported | 52.14 | standard |
Comparability of the trials
- FlagBaseline, Baseline BMI or body weight: design means range from 31.8 (MAZD_SC_3MG_QW vs MAZD_SC_4p5MG_QW vs MAZD_SC_6MG_QW vs PLACEBO) to 46.0 (LIRA_SC_3p0MG_QD vs STANDARD_CARE) kg/m2; threshold 3
- FlagBaseline, Type 2 diabetes share in weight trials: design means range from 0.0 (BOFANG_SC_12MG_Q2W vs BOFANG_SC_18MG_Q2W vs BOFANG_SC_24MG_Q2W vs BOFANG_SC_24MG_QW vs BOFANG_SC_48MG_Q2W vs PLACEBO) to 35.5 (LIRA_SC_3p0MG_QD vs STANDARD_CARE) percent of participants; threshold 20
- FlagBaseline, Sex: design means range from 45.6 (BOFANG_SC_12MG_Q2W vs BOFANG_SC_18MG_Q2W vs BOFANG_SC_24MG_Q2W vs BOFANG_SC_24MG_QW vs BOFANG_SC_48MG_Q2W vs PLACEBO) to 80.6 (PLACEBO vs SEMA_SC_2p4MG_QW) percent female; threshold 15
- FlagBaseline, Asian ancestry or region: not reported by 4 of 13 trials
- FlagBaseline, Asian ancestry or region: design means range from 0.7 (ORFO_PO_12MG_QD vs ORFO_PO_24MG_QD vs ORFO_PO_36MG_QD vs ORFO_PO_45MG_QD vs PLACEBO) to 100.0 (BOFANG_SC_12MG_Q2W vs BOFANG_SC_18MG_Q2W vs BOFANG_SC_24MG_Q2W vs BOFANG_SC_24MG_QW vs BOFANG_SC_48MG_Q2W vs PLACEBO) percent Asian; threshold 30
- FlagBaseline, Treatment duration: design means range from 20.0 (EFPE_SC_4MG_QW vs EFPE_SC_6MG_Q2W vs EFPE_SC_6MG_QW vs EFPE_SC_8MG_Q2W vs PLACEBO) to 104.0 (LIRA_SC_3p0MG_QD vs STANDARD_CARE) weeks; threshold 26
- FlagHeterogeneity, tau above threshold: tau 3.50 exceeds the outcome threshold 2.5; the flags of this network are candidate explanations
- NoteOutcome assessment, time point: selected time points span 20 to 32 weeks
- NoteOutcome assessment, analysis set: mixed: completers 2, full_analysis 3, modified_itt 5, randomized 3
- NoteRisk of bias, blinding: mixed: double_blind 12, open_label 1
- NoteRisk of bias, funding: mixed: industry 11, mixed 2
- NoteData handling, input conversions: arms_combined 1, n_randomized 19
| Trial | time weeks | analysis set | definition | instrument | adjudicated | proportion method | intercurrent events (discontinuation) | intercurrent events (rescue) | blinding | funding | start year | Eligibility |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| BARI-STEP | 32 | randomized | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | mixed | 2022 | age 18 to 65; at least 1 year after primary bypass or sleeve; less than 20 percent weight loss from surgery |
| BARIOPTIMISE | 24 | modified_itt | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | mixed | 2018 | adults at least 1 year after RYGB or sleeve gastrectomy with 20 percent or less weight loss and suboptimal GLP-1 response |
| NCT00500370 | 24 | modified_itt | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2007 | adults with BMI 30 or more, without diabetes |
| NCT02075281 | 20 | full_analysis | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2014 | age 18 to 64 years; BMI 30 to 42, or 27 to 30 with comorbidity; FPG below 7 mmol/L; HbA1c 6.5 percent or less; no diabetes |
| NCT04904913 | 24 | modified_itt | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2021 | Chinese adults 18 to 75; BMI 28 or more, or 24 or more with comorbidity or hyperphagia; no diabetes, HbA1c below 6.5 |
| Dapalost | 24 | full_analysis | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2014 | age 18 to 70; BMI 30 to 45 kg/m2; no diabetes |
| STABLE Wt Loss | 20 | randomized | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2022 | age 18 to 70; BMI 30 or more, or 27 or more with comorbidity; no diabetes; HbA1c 6.5 percent or less |
| NCT05623839 | 27 | completers | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2022 | age 18 to 70; BMI 27 to 50; HbA1c below 6.5 percent; no diabetes |
| STRIVE | 32 | completers | not stated | not stated | not stated | not stated | not stated | not stated | open_label | industry | 2017 | age 18 to 75; BMI 35 or more plus prediabetes, T2D, hypertension or sleep apnea; no insulin or GLP-1 RA |
| NCT01557166 | 32 | full_analysis | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2012 | age 18 to 64; BMI 30 or more; AHI 15 or more; no diabetes; unable or unwilling to use CPAP |
| NCT05051579 | 26 | modified_itt | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2021 | adults BMI 30 or more, or 27 to 30 with a weight related complication, without diabetes |
| NCT06256562 | 30 | modified_itt | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2023 | age 18 to 75; BMI 24 to <28 kg/m2 with comorbidity or 28 or more (Chinese criteria); no diabetes |
| S003017 | 26.07 | randomized | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2019 | age 20 to 65; BMI above 35; 12 to 36 months after bariatric surgery with suboptimal stable weight loss or regain |
Trial data
| Trial | Arm | Treatment | Week | Data | Value | SE | Events / N | Flags | Source |
|---|---|---|---|---|---|---|---|---|---|
| BARI-STEP | A1 | PLACEBO | 32 | arm, percent_change | 0.710 | 1.330 | 30 | R0014003:Supplement Table 6 | |
| BARI-STEP | A2 | SEMA_SC_2p4MG_QW | 32 | arm, percent_change | -12.960 | 1.340 | 34 | R0014003:Supplement Table 6 | |
| BARIOPTIMISE | A1 | PLACEBO | 24 | arm, percent_change | -0.540 | 0.651 | 26 | R0017334:Results | |
| BARIOPTIMISE | A2 | LIRA_SC_3p0MG_QD | 24 | arm, percent_change | -8.820 | 0.887 | 31 | R0017334:Results | |
| NCT00500370 | A1 | EXEN_SC_10UG_BID | 24 | contrast, md | -3.300 | 0.500 | R0026955:Results | ||
| NCT00500370 | A2 | PLACEBO | 24 | contrast, md | R0026955:Results | ||||
| NCT02075281 | A1 | PLACEBO | 20 | arm, percent_change | 0.100 | 0.600 | 60 | n_randomized | R0011218:Table 2 |
| NCT02075281 | A2 | EFPE_SC_4MG_QW | 20 | arm, percent_change | -6.700 | 0.600 | 59 | n_randomized | R0011218:Table 2 |
| NCT02075281 | A3 | EFPE_SC_6MG_QW | 20 | arm, percent_change | -7.300 | 0.600 | 59 | n_randomized | R0011218:Table 2 |
| NCT02075281 | A4 | EFPE_SC_6MG_Q2W | 20 | arm, percent_change | -6.700 | 0.600 | 59 | n_randomized | R0011218:Table 2 |
| NCT02075281 | A5 | EFPE_SC_8MG_Q2W | 20 | arm, percent_change | -7.400 | 0.600 | 60 | n_randomized | R0011218:Table 2 |
| NCT04904913 | A1 | MAZD_SC_3MG_QW | 24 | arm, percent_change | -6.700 | 0.700 | 62 | R0016107:Table 2 | |
| NCT04904913 | A2 | MAZD_SC_4p5MG_QW | 24 | arm, percent_change | -10.400 | 0.700 | 63 | R0016107:Table 2 | |
| NCT04904913 | A3 | MAZD_SC_6MG_QW | 24 | arm, percent_change | -11.300 | 0.700 | 61 | R0016107:Table 2 | |
| NCT04904913 | A4 | PLACEBO | 24 | arm, percent_change | 1.000 | 0.700 | 62 | R0016107:Table 2 | |
| Dapalost | A1 | EXENER_SC_2-10MG_QW | 24 | arm, percent_change | -4.470 | 0.804 | 25 | n_randomized | R0025627:Table 2 |
| Dapalost | A2 | PLACEBO | 24 | arm, percent_change | -0.270 | 0.839 | 25 | n_randomized | R0025627:Table 2 |
| STABLE Wt Loss | A1 | SEMA_SC_2p4MG_QW | 20 | arm, percent_change | -9.700 | 0.600 | 72 | n_randomized | R0013679:Table 3 |
| STABLE Wt Loss | A2 | PLACEBO | 20 | arm, percent_change | -4.700 | 0.900 | 48 | n_randomized | R0013679:Table 3 |
| NCT05623839 | A1 | PLACEBO | 27 | arm, percent_change | 1.200 | 1.600 | 6 | R0013210:Results | |
| NCT05623839 | A2+A3 | MAZD_SC_16MG_QW | 27 | arm, percent_change | -14.100 | 0.860 | 21 | arms_combined | R0013210:Results |
| STRIVE | A1 | STANDARD_CARE | 32 | arm, percent_change | -4.580 | 0.646 | 79 | registry:outcomes | |
| STRIVE | A2 | LIRA_SC_3p0MG_QD | 32 | arm, percent_change | -9.000 | 0.404 | 208 | registry:outcomes | |
| NCT01557166 | A1 | LIRA_SC_3p0MG_QD | 32 | arm, percent_change | -5.700 | 0.400 | 180 | n_randomized | R0026203:Results |
| NCT01557166 | A2 | PLACEBO | 32 | arm, percent_change | -1.600 | 0.300 | 179 | n_randomized | R0026203:Results |
| NCT05051579 | A1 | ORFO_PO_12MG_QD | 26 | arm, percent_change | -8.600 | 0.850 | 44 | registry:outcomes | |
| NCT05051579 | A2 | ORFO_PO_24MG_QD | 26 | arm, percent_change | -11.200 | 0.820 | 51 | registry:outcomes | |
| NCT05051579 | A3 | ORFO_PO_36MG_QD | 26 | arm, percent_change | -12.300 | 0.770 | 56 | registry:outcomes | |
| NCT05051579 | A5 | ORFO_PO_45MG_QD | 26 | arm, percent_change | -12.600 | 0.750 | 57 | registry:outcomes | |
| NCT05051579 | A7 | PLACEBO | 26 | arm, percent_change | -2.000 | 0.810 | 48 | registry:outcomes | |
| NCT06256562 | A1 | BOFANG_SC_12MG_Q2W | 30 | arm, percent_change | -9.720 | 0.940 | 52 | n_randomized | R0002409:Supplement Table S2 |
| NCT06256562 | A2 | BOFANG_SC_18MG_Q2W | 30 | arm, percent_change | -12.500 | 0.930 | 53 | n_randomized | R0002409:Supplement Table S2 |
| NCT06256562 | A3 | BOFANG_SC_24MG_Q2W | 30 | arm, percent_change | -13.340 | 0.940 | 52 | n_randomized | R0002409:Supplement Table S2 |
| NCT06256562 | A4 | BOFANG_SC_48MG_Q2W | 30 | arm, percent_change | -17.570 | 0.870 | 64 | n_randomized | R0002409:Supplement Table S2 |
| NCT06256562 | A5 | BOFANG_SC_24MG_QW | 30 | arm, percent_change | -16.280 | 0.930 | 53 | n_randomized | R0002409:Supplement Table S2 |
| NCT06256562 | A6 | PLACEBO | 30 | arm, percent_change | -0.930 | 0.830 | 66 | n_randomized | R0002409:Supplement Table S2 |
| S003017 | A1 | LIRA_SC_3p0MG_QD | 26.07 | arm, percent_change | -3.490 | 0.790 | 24 | n_randomized | R0016758:Supplement eTable 1 |
| S003017 | A2 | PLACEBO | 26.07 | arm, percent_change | -0.160 | 0.880 | 24 | n_randomized | R0016758:Supplement eTable 1 |
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