Network meta-analysis
Level 2 or 3 hypoglycemia (participants)
Type 2 diabetes (adults)
longest follow-upRecorded harmsDoses of a drug pooledHazard ratio (from event counts)
38
Randomized trials
27
Treatments
18,205
Participants
5,236
Events
In plain language
Across 38 trials with 18,205 participants, 1 of 26 treatments had a clearly better result than placebo on level 2 or 3 hypoglycemia (participants), 12 a clearly worse one, and for 13 the evidence could not tell them apart from placebo. The most favorable estimate was for Sitagliptin: hazard ratio (from event counts) 0.11 (95% credible interval 0.01 to 0.66).
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
Hazard ratio (from event counts). Lower values favor the treatment.
| Treatment | Bayesian HR (95% CrI) | 95% prediction interval | Frequentist HR (95% CI) | Verdict |
|---|---|---|---|---|
| Sitagliptin SITAGLIPTIN | 0.11 (0.01 to 0.66) | 0.01 to 0.69 | Better | |
| Efpe sc EFPE_SC | 0.38 (0.00 to 23.41) | 0.00 to 23.40 | Unclear | |
| Polyethylene glycol loxenatide injection PEGLOX_SC | 0.46 (0.02 to 10.76) | 0.02 to 11.13 | Unclear | |
| Exenatide extended release injection EXENER_SC | 0.52 (0.00 to 37.23) | 0.00 to 37.87 | Unclear | |
| Metformin METFORMIN | 0.58 (0.02 to 15.90) | 0.02 to 16.78 | Unclear | |
| Lixisenatide injection LIXI_SC | 0.64 (0.30 to 1.36) | 0.27 to 1.47 | Unclear | |
| Basal insulin sglt2i OTHER_ACTIVE_basal_insulin_sglt2i | 1.60 (0.22 to 12.54) | 0.21 to 13.08 | Unclear | |
| Tirzepatide injection TIRZ_SC | 1.86 (0.94 to 3.95) | 0.88 to 4.37 | Unclear | |
| Dulaglutide injection DULA_SC | 1.95 (1.05 to 3.60) | 0.93 to 3.92 | Worse | |
| Standard care or no added treatment STANDARD_CARE | 2.13 (0.79 to 5.73) | 0.73 to 5.99 | Unclear | |
| HRS-7535 tablet HRS7535_PO | 2.40 (1.03 to 6.15) | 0.94 to 6.63 | Worse | |
| Semaglutide injection SEMA_SC | 2.42 (0.73 to 7.47) | 0.69 to 7.84 | Unclear | |
| Liraglutide injection LIRA_SC | 2.46 (1.01 to 5.77) | 0.91 to 6.12 | Worse | |
| Investigator choice oral drug OTHER_ACTIVE_investigator_choice_oral_drug | 2.57 (0.89 to 6.85) | 0.82 to 7.30 | Unclear | |
| Albiglutide injection ALBI_SC | 2.82 (1.39 to 5.60) | 1.25 to 6.20 | Worse | |
| Bofanglutide (GZR18) injection BOFANG_SC | 3.06 (0.18 to 106) | 0.17 to 108 | Unclear | |
| Dapagliflozin DAPAGLIFLOZIN | 3.40 (1.14 to 10.03) | 1.06 to 10.63 | Worse | |
| Insulin glargine with lixisenatide injection IGLARLIXI_SC | 3.82 (1.96 to 7.38) | 1.74 to 8.03 | Worse | |
| Insulin glargine INS_GLARGINE | 3.83 (2.01 to 7.20) | 1.77 to 7.77 | Worse | |
| Exenatide injection EXEN_SC | 4.42 (1.60 to 12.27) | 1.43 to 12.70 | Worse | |
| Danuglipron tablet DANU_PO | 4.52 (0.52 to 107) | 0.48 to 110 | Unclear | |
| Basal bolus insulin OTHER_ACTIVE_basal_bolus_insulin | 4.67 (0.74 to 32.58) | 0.72 to 33.59 | Unclear | |
| Insulin aspart (prandial) INS_ASPART | 4.75 (1.59 to 13.85) | 1.47 to 14.72 | Worse | |
| Insulin lispro (prandial) INS_LISPRO | 4.89 (2.43 to 10.28) | 2.19 to 11.11 | Worse | |
| Glimepiride GLIMEPIRIDE | 10.47 (4.25 to 26.79) | 3.81 to 28.23 | Worse | |
| Premixed insulin INS_PREMIX | 12.19 (2.63 to 61.77) | 2.53 to 63.67 | Worse |
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: hazard ratio (from event counts) 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 | SITAGLIPTIN | EFPE_SC | PEGLOX_SC | EXENER_SC | METFORMIN | LIXI_SC | OTHER_ACTIVE_basal_insulin_sglt2i | TIRZ_SC | DULA_SC | STANDARD_CARE | HRS7535_PO | SEMA_SC | LIRA_SC | OTHER_ACTIVE_investigator_choice_oral_drug | ALBI_SC | BOFANG_SC | DAPAGLIFLOZIN | IGLARLIXI_SC | INS_GLARGINE | EXEN_SC | DANU_PO | OTHER_ACTIVE_basal_bolus_insulin | INS_ASPART | INS_LISPRO | GLIMEPIRIDE | INS_PREMIX |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PLACEBO | PLACEBO | 9.19 1.52 to 92.66 | 2.65 0.04 to 209 | 2.17 0.09 to 54.30 | 1.93 0.03 to 202 | 1.71 0.06 to 45.87 | 1.55 0.74 to 3.35 | 0.63 0.08 to 4.52 | 0.54 0.25 to 1.06 | 0.51 0.28 to 0.95 | 0.47 0.17 to 1.27 | 0.42 0.16 to 0.97 | 0.41 0.13 to 1.38 | 0.41 0.17 to 0.99 | 0.39 0.15 to 1.12 | 0.35 0.18 to 0.72 | 0.33 0.01 to 5.45 | 0.29 0.10 to 0.87 | 0.26 0.14 to 0.51 | 0.26 0.14 to 0.50 | 0.23 0.08 to 0.63 | 0.22 0.01 to 1.94 | 0.21 0.03 to 1.35 | 0.21 0.07 to 0.63 | 0.20 0.10 to 0.41 | 0.10 0.04 to 0.24 | 0.08 0.02 to 0.38 |
| SITAGLIPTIN | 0.11 0.01 to 0.66 | SITAGLIPTIN | 0.27 0.00 to 29.64 | 0.22 0.00 to 8.91 | 0.20 0.00 to 29.99 | 0.17 0.00 to 7.62 | 0.17 0.02 to 0.91 | 0.06 0.00 to 0.89 | 0.06 0.01 to 0.36 | 0.06 0.01 to 0.33 | 0.05 0.00 to 0.37 | 0.04 0.00 to 0.33 | 0.04 0.00 to 0.38 | 0.04 0.00 to 0.31 | 0.04 0.00 to 0.33 | 0.04 0.00 to 0.23 | 0.03 0.00 to 1.03 | 0.03 0.00 to 0.25 | 0.03 0.00 to 0.16 | 0.03 0.00 to 0.16 | 0.02 0.00 to 0.18 | 0.02 0.00 to 0.41 | 0.02 0.00 to 0.28 | 0.02 0.00 to 0.18 | 0.02 0.00 to 0.14 | 0.01 0.00 to 0.07 | 0.01 0.00 to 0.09 |
| EFPE_SC | 0.38 0.00 to 23.41 | 3.66 0.03 to 417 | EFPE_SC | 0.79 0.00 to 174 | 0.73 0.00 to 363 | 0.63 0.00 to 130 | 0.59 0.01 to 38.60 | 0.23 0.00 to 22.28 | 0.20 0.00 to 12.95 | 0.19 0.00 to 12.82 | 0.18 0.00 to 12.43 | 0.15 0.00 to 10.91 | 0.16 0.00 to 11.67 | 0.16 0.00 to 10.39 | 0.15 0.00 to 10.20 | 0.14 0.00 to 8.70 | 0.12 0.00 to 19.95 | 0.11 0.00 to 7.59 | 0.10 0.00 to 6.28 | 0.10 0.00 to 6.29 | 0.09 0.00 to 5.89 | 0.07 0.00 to 8.91 | 0.08 0.00 to 7.26 | 0.08 0.00 to 5.70 | 0.08 0.00 to 4.80 | 0.04 0.00 to 2.49 | 0.03 0.00 to 2.66 |
| PEGLOX_SC | 0.46 0.02 to 10.76 | 4.53 0.11 to 202 | 1.27 0.01 to 261 | PEGLOX_SC | 0.88 0.00 to 232 | 0.77 0.12 to 5.61 | 0.72 0.03 to 17.93 | 0.28 0.01 to 11.60 | 0.25 0.01 to 6.14 | 0.24 0.01 to 5.87 | 0.22 0.01 to 5.95 | 0.19 0.01 to 5.09 | 0.19 0.01 to 5.86 | 0.19 0.01 to 5.21 | 0.18 0.01 to 5.25 | 0.17 0.01 to 4.22 | 0.15 0.00 to 10.81 | 0.13 0.00 to 4.13 | 0.12 0.00 to 3.14 | 0.12 0.00 to 3.05 | 0.10 0.00 to 2.94 | 0.09 0.00 to 5.02 | 0.10 0.00 to 3.68 | 0.10 0.00 to 2.94 | 0.10 0.00 to 2.41 | 0.04 0.00 to 1.21 | 0.04 0.00 to 1.27 |
| EXENER_SC | 0.52 0.00 to 37.23 | 5.10 0.03 to 613 | 1.36 0.00 to 680 | 1.14 0.00 to 208 | EXENER_SC | 0.89 0.00 to 204 | 0.81 0.01 to 61.69 | 0.33 0.00 to 35.17 | 0.27 0.00 to 21.14 | 0.26 0.00 to 18.96 | 0.25 0.00 to 19.21 | 0.22 0.00 to 16.17 | 0.22 0.00 to 17.70 | 0.21 0.00 to 16.91 | 0.21 0.00 to 16.50 | 0.18 0.00 to 13.81 | 0.16 0.00 to 30.96 | 0.15 0.00 to 11.84 | 0.14 0.00 to 10.09 | 0.13 0.00 to 10.11 | 0.12 0.00 to 9.85 | 0.10 0.00 to 14.53 | 0.11 0.00 to 11.49 | 0.11 0.00 to 8.75 | 0.11 0.00 to 7.87 | 0.05 0.00 to 4.01 | 0.04 0.00 to 4.20 |
| METFORMIN | 0.58 0.02 to 15.90 | 5.73 0.13 to 275 | 1.59 0.01 to 346 | 1.30 0.18 to 8.06 | 1.13 0.00 to 311 | METFORMIN | 0.89 0.03 to 26.38 | 0.36 0.01 to 16.91 | 0.31 0.01 to 9.09 | 0.29 0.01 to 8.62 | 0.27 0.01 to 8.80 | 0.24 0.01 to 7.25 | 0.24 0.01 to 8.03 | 0.24 0.01 to 7.13 | 0.23 0.01 to 7.10 | 0.21 0.01 to 6.38 | 0.19 0.00 to 14.48 | 0.17 0.01 to 5.79 | 0.15 0.01 to 4.37 | 0.15 0.01 to 4.23 | 0.13 0.00 to 4.24 | 0.12 0.00 to 7.03 | 0.12 0.00 to 5.66 | 0.12 0.00 to 3.93 | 0.12 0.00 to 3.53 | 0.06 0.00 to 1.75 | 0.05 0.00 to 1.81 |
| LIXI_SC | 0.64 0.30 to 1.36 | 5.89 1.10 to 55.49 | 1.70 0.03 to 146 | 1.39 0.06 to 35.00 | 1.24 0.02 to 135 | 1.12 0.04 to 31.29 | LIXI_SC | 0.40 0.05 to 2.82 | 0.35 0.14 to 0.68 | 0.33 0.20 to 0.54 | 0.30 0.11 to 0.82 | 0.26 0.08 to 0.80 | 0.26 0.08 to 0.91 | 0.26 0.10 to 0.66 | 0.25 0.09 to 0.76 | 0.23 0.12 to 0.42 | 0.21 0.01 to 3.79 | 0.19 0.06 to 0.58 | 0.17 0.11 to 0.25 | 0.17 0.11 to 0.25 | 0.15 0.05 to 0.42 | 0.14 0.01 to 1.39 | 0.14 0.02 to 0.87 | 0.13 0.04 to 0.44 | 0.13 0.06 to 0.25 | 0.06 0.02 to 0.16 | 0.05 0.01 to 0.26 |
| OTHER_ACTIVE_basal_insulin_sglt2i | 1.60 0.22 to 12.54 | 15.69 1.12 to 310 | 4.40 0.04 to 534 | 3.56 0.09 to 153 | 3.08 0.03 to 459 | 2.77 0.06 to 135 | 2.48 0.35 to 20.39 | OTHER_ACTIVE_basal_insulin_sglt2i | 0.85 0.11 to 6.94 | 0.82 0.12 to 6.26 | 0.74 0.09 to 6.93 | 0.67 0.08 to 6.16 | 0.66 0.07 to 6.76 | 0.65 0.08 to 5.71 | 0.62 0.07 to 6.09 | 0.57 0.08 to 4.60 | 0.51 0.01 to 18.52 | 0.47 0.06 to 4.38 | 0.42 0.06 to 3.36 | 0.42 0.06 to 3.29 | 0.36 0.04 to 3.35 | 0.33 0.01 to 7.30 | 0.35 0.14 to 0.78 | 0.34 0.04 to 3.23 | 0.33 0.04 to 2.71 | 0.15 0.02 to 1.33 | 0.13 0.01 to 1.55 |
| TIRZ_SC | 1.86 0.94 to 3.95 | 17.31 2.81 to 196 | 4.96 0.08 to 417 | 4.01 0.16 to 104 | 3.69 0.05 to 396 | 3.24 0.11 to 92.72 | 2.86 1.47 to 6.95 | 1.18 0.14 to 9.00 | TIRZ_SC | 0.94 0.54 to 2.01 | 0.87 0.31 to 2.63 | 0.77 0.24 to 2.40 | 0.76 0.23 to 2.93 | 0.75 0.30 to 2.23 | 0.71 0.25 to 2.48 | 0.65 0.42 to 1.25 | 0.61 0.02 to 11.04 | 0.54 0.17 to 1.92 | 0.48 0.28 to 1.07 | 0.48 0.28 to 1.02 | 0.42 0.15 to 1.39 | 0.41 0.02 to 4.00 | 0.40 0.05 to 2.58 | 0.39 0.12 to 1.38 | 0.38 0.27 to 0.60 | 0.18 0.07 to 0.51 | 0.15 0.03 to 0.82 |
| DULA_SC | 1.95 1.05 to 3.60 | 17.97 3.04 to 179 | 5.22 0.08 to 427 | 4.18 0.17 to 108 | 3.79 0.05 to 409 | 3.39 0.12 to 91.02 | 3.04 1.84 to 5.01 | 1.22 0.16 to 8.40 | 1.07 0.50 to 1.85 | DULA_SC | 0.92 0.38 to 2.13 | 0.81 0.26 to 2.24 | 0.80 0.28 to 2.45 | 0.79 0.37 to 1.77 | 0.76 0.30 to 2.04 | 0.70 0.40 to 1.13 | 0.64 0.02 to 11.38 | 0.57 0.21 to 1.56 | 0.51 0.36 to 0.71 | 0.51 0.38 to 0.66 | 0.44 0.18 to 1.10 | 0.42 0.02 to 4.18 | 0.42 0.06 to 2.44 | 0.41 0.15 to 1.16 | 0.40 0.20 to 0.69 | 0.19 0.08 to 0.42 | 0.16 0.03 to 0.70 |
| STANDARD_CARE | 2.13 0.79 to 5.73 | 20.14 2.71 to 217 | 5.63 0.08 to 493 | 4.55 0.17 to 125 | 4.03 0.05 to 444 | 3.66 0.11 to 107 | 3.29 1.22 to 9.08 | 1.34 0.14 to 10.61 | 1.15 0.38 to 3.23 | 1.09 0.47 to 2.63 | STANDARD_CARE | 0.88 0.22 to 3.12 | 0.87 0.29 to 2.73 | 0.87 0.39 to 1.94 | 0.83 0.32 to 2.19 | 0.76 0.28 to 2.06 | 0.71 0.02 to 13.97 | 0.63 0.22 to 1.79 | 0.55 0.22 to 1.43 | 0.56 0.22 to 1.39 | 0.48 0.16 to 1.48 | 0.46 0.02 to 5.16 | 0.46 0.06 to 3.17 | 0.44 0.16 to 1.31 | 0.43 0.15 to 1.23 | 0.20 0.07 to 0.56 | 0.18 0.03 to 0.88 |
| HRS7535_PO | 2.40 1.03 to 6.15 | 22.91 3.03 to 263 | 6.54 0.09 to 537 | 5.31 0.20 to 155 | 4.59 0.06 to 498 | 4.14 0.14 to 135 | 3.78 1.26 to 12.51 | 1.50 0.16 to 13.30 | 1.29 0.42 to 4.11 | 1.23 0.45 to 3.84 | 1.14 0.32 to 4.55 | HRS7535_PO | 1.00 0.24 to 4.48 | 0.99 0.29 to 3.56 | 0.95 0.26 to 3.81 | 0.86 0.29 to 2.80 | 0.80 0.02 to 15.43 | 0.72 0.18 to 3.04 | 0.63 0.22 to 2.03 | 0.63 0.23 to 1.98 | 0.55 0.15 to 2.18 | 0.53 0.02 to 5.96 | 0.52 0.06 to 4.21 | 0.52 0.13 to 2.14 | 0.49 0.16 to 1.61 | 0.23 0.07 to 0.85 | 0.20 0.03 to 1.22 |
| SEMA_SC | 2.42 0.73 to 7.47 | 23.14 2.64 to 268 | 6.22 0.09 to 598 | 5.26 0.17 to 144 | 4.59 0.06 to 558 | 4.15 0.12 to 127 | 3.80 1.10 to 12.12 | 1.52 0.15 to 13.34 | 1.32 0.34 to 4.27 | 1.24 0.41 to 3.63 | 1.15 0.37 to 3.47 | 1.00 0.22 to 4.09 | SEMA_SC | 0.99 0.44 to 2.23 | 0.94 0.36 to 2.45 | 0.87 0.25 to 2.77 | 0.79 0.02 to 16.18 | 0.71 0.24 to 2.05 | 0.64 0.19 to 1.96 | 0.64 0.20 to 1.93 | 0.55 0.16 to 1.84 | 0.52 0.02 to 6.19 | 0.52 0.06 to 4.09 | 0.51 0.33 to 0.77 | 0.50 0.14 to 1.62 | 0.23 0.07 to 0.71 | 0.20 0.03 to 1.09 |
| LIRA_SC | 2.46 1.01 to 5.77 | 23.00 3.26 to 252 | 6.44 0.10 to 594 | 5.37 0.19 to 142 | 4.67 0.06 to 526 | 4.20 0.14 to 125 | 3.85 1.51 to 9.68 | 1.54 0.18 to 12.00 | 1.33 0.45 to 3.35 | 1.26 0.56 to 2.71 | 1.15 0.52 to 2.56 | 1.01 0.28 to 3.43 | 1.01 0.45 to 2.25 | LIRA_SC | 0.95 0.56 to 1.66 | 0.88 0.34 to 2.11 | 0.81 0.02 to 15.11 | 0.72 0.36 to 1.42 | 0.65 0.27 to 1.47 | 0.64 0.28 to 1.44 | 0.56 0.22 to 1.38 | 0.53 0.02 to 5.56 | 0.53 0.07 to 3.68 | 0.52 0.26 to 1.03 | 0.51 0.18 to 1.27 | 0.24 0.10 to 0.51 | 0.20 0.04 to 0.90 |
| OTHER_ACTIVE_investigator_choice_oral_drug | 2.57 0.89 to 6.85 | 24.21 3.00 to 275 | 6.77 0.10 to 642 | 5.60 0.19 to 149 | 4.86 0.06 to 580 | 4.40 0.14 to 140 | 4.04 1.31 to 11.45 | 1.61 0.16 to 13.52 | 1.40 0.40 to 3.96 | 1.32 0.49 to 3.30 | 1.21 0.46 to 3.10 | 1.05 0.26 to 3.86 | 1.06 0.41 to 2.80 | 1.05 0.60 to 1.79 | OTHER_ACTIVE_investigator_choice_oral_drug | 0.92 0.31 to 2.54 | 0.86 0.02 to 16.97 | 0.76 0.31 to 1.81 | 0.68 0.24 to 1.79 | 0.68 0.24 to 1.74 | 0.59 0.20 to 1.69 | 0.55 0.02 to 6.34 | 0.56 0.06 to 4.02 | 0.54 0.22 to 1.31 | 0.53 0.16 to 1.49 | 0.25 0.09 to 0.63 | 0.21 0.04 to 1.08 |
| ALBI_SC | 2.82 1.39 to 5.60 | 26.16 4.26 to 268 | 7.39 0.11 to 596 | 5.97 0.24 to 154 | 5.42 0.07 to 594 | 4.87 0.16 to 138 | 4.33 2.40 to 8.41 | 1.74 0.22 to 13.04 | 1.53 0.80 to 2.36 | 1.43 0.89 to 2.48 | 1.32 0.48 to 3.57 | 1.16 0.36 to 3.42 | 1.15 0.36 to 4.05 | 1.14 0.47 to 2.92 | 1.09 0.39 to 3.27 | ALBI_SC | 0.91 0.03 to 16.36 | 0.82 0.27 to 2.56 | 0.73 0.46 to 1.25 | 0.73 0.47 to 1.18 | 0.63 0.23 to 1.83 | 0.60 0.02 to 5.93 | 0.61 0.08 to 3.81 | 0.59 0.19 to 1.94 | 0.58 0.37 to 0.83 | 0.27 0.10 to 0.68 | 0.23 0.04 to 1.12 |
| BOFANG_SC | 3.06 0.18 to 106 | 30.53 0.97 to 1880 | 8.37 0.05 to 2296 | 6.78 0.09 to 743 | 6.16 0.03 to 1625 | 5.27 0.07 to 721 | 4.80 0.26 to 177 | 1.95 0.05 to 115 | 1.64 0.09 to 58.15 | 1.57 0.09 to 56.81 | 1.42 0.07 to 53.90 | 1.25 0.06 to 45.42 | 1.26 0.06 to 49.17 | 1.24 0.07 to 46.42 | 1.17 0.06 to 46.60 | 1.09 0.06 to 39.17 | BOFANG_SC | 0.90 0.05 to 37.07 | 0.81 0.05 to 29.14 | 0.81 0.04 to 28.73 | 0.69 0.03 to 26.12 | 0.63 0.01 to 39.13 | 0.66 0.02 to 35.53 | 0.64 0.03 to 25.21 | 0.63 0.03 to 23.04 | 0.29 0.01 to 10.77 | 0.25 0.01 to 11.63 |
| DAPAGLIFLOZIN | 3.40 1.14 to 10.03 | 31.90 3.94 to 370 | 8.94 0.13 to 838 | 7.44 0.24 to 209 | 6.46 0.08 to 783 | 5.73 0.17 to 184 | 5.31 1.73 to 16.38 | 2.13 0.23 to 17.85 | 1.84 0.52 to 5.77 | 1.74 0.64 to 4.86 | 1.59 0.56 to 4.48 | 1.40 0.33 to 5.46 | 1.40 0.49 to 4.09 | 1.38 0.71 to 2.75 | 1.32 0.55 to 3.18 | 1.22 0.39 to 3.70 | 1.12 0.03 to 22.10 | DAPAGLIFLOZIN | 0.90 0.31 to 2.61 | 0.89 0.31 to 2.55 | 0.77 0.25 to 2.37 | 0.73 0.03 to 8.49 | 0.74 0.08 to 5.45 | 0.71 0.27 to 1.95 | 0.70 0.21 to 2.17 | 0.33 0.11 to 0.92 | 0.28 0.05 to 1.46 |
| IGLARLIXI_SC | 3.82 1.96 to 7.38 | 34.81 6.08 to 344 | 10.11 0.16 to 827 | 8.20 0.32 to 206 | 7.38 0.10 to 830 | 6.58 0.23 to 179 | 5.91 3.94 to 9.04 | 2.39 0.30 to 16.50 | 2.08 0.93 to 3.63 | 1.95 1.40 to 2.77 | 1.80 0.70 to 4.53 | 1.58 0.49 to 4.48 | 1.56 0.51 to 5.16 | 1.54 0.68 to 3.68 | 1.47 0.56 to 4.18 | 1.36 0.80 to 2.19 | 1.24 0.03 to 21.60 | 1.12 0.38 to 3.26 | IGLARLIXI_SC | 1.00 0.82 to 1.21 | 0.86 0.33 to 2.29 | 0.82 0.03 to 8.07 | 0.82 0.12 to 4.99 | 0.79 0.28 to 2.46 | 0.79 0.40 to 1.34 | 0.36 0.15 to 0.86 | 0.31 0.06 to 1.44 |
| INS_GLARGINE | 3.83 2.01 to 7.20 | 34.95 6.10 to 339 | 10.10 0.16 to 834 | 8.28 0.33 to 205 | 7.41 0.10 to 817 | 6.61 0.24 to 180 | 5.93 3.93 to 9.13 | 2.39 0.30 to 16.53 | 2.09 0.98 to 3.54 | 1.95 1.50 to 2.63 | 1.80 0.72 to 4.45 | 1.59 0.50 to 4.41 | 1.57 0.52 to 5.04 | 1.55 0.69 to 3.63 | 1.48 0.58 to 4.13 | 1.37 0.84 to 2.14 | 1.24 0.03 to 22.26 | 1.12 0.39 to 3.20 | 1.00 0.83 to 1.22 | INS_GLARGINE | 0.87 0.33 to 2.22 | 0.82 0.03 to 8.08 | 0.83 0.12 to 4.94 | 0.80 0.28 to 2.41 | 0.79 0.42 to 1.31 | 0.37 0.15 to 0.83 | 0.31 0.06 to 1.41 |
| EXEN_SC | 4.42 1.60 to 12.27 | 41.54 5.44 to 472 | 11.75 0.17 to 1083 | 9.53 0.34 to 278 | 8.33 0.10 to 974 | 7.53 0.24 to 234 | 6.88 2.39 to 19.26 | 2.75 0.30 to 22.47 | 2.38 0.72 to 6.89 | 2.25 0.91 to 5.69 | 2.08 0.68 to 6.35 | 1.82 0.46 to 6.84 | 1.83 0.54 to 6.18 | 1.79 0.72 to 4.52 | 1.71 0.59 to 5.04 | 1.58 0.55 to 4.39 | 1.45 0.04 to 29.21 | 1.30 0.42 to 4.08 | 1.16 0.44 to 3.06 | 1.15 0.45 to 2.99 | EXEN_SC | 0.94 0.04 to 10.33 | 0.94 0.12 to 6.99 | 0.93 0.29 to 2.92 | 0.91 0.29 to 2.60 | 0.42 0.26 to 0.64 | 0.37 0.09 to 1.23 |
| DANU_PO | 4.52 0.52 to 107 | 47.42 2.44 to 1715 | 13.75 0.11 to 2522 | 10.82 0.20 to 880 | 9.59 0.07 to 2335 | 8.55 0.14 to 794 | 7.22 0.72 to 182 | 3.07 0.14 to 104 | 2.46 0.25 to 59.24 | 2.37 0.24 to 58.17 | 2.17 0.19 to 55.50 | 1.87 0.17 to 48.06 | 1.91 0.16 to 54.67 | 1.88 0.18 to 48.47 | 1.83 0.16 to 52.33 | 1.65 0.17 to 40.15 | 1.58 0.03 to 91.82 | 1.36 0.12 to 36.50 | 1.21 0.12 to 29.63 | 1.22 0.12 to 29.10 | 1.07 0.10 to 27.63 | DANU_PO | 1.06 0.05 to 32.62 | 0.98 0.08 to 26.19 | 0.95 0.09 to 23.00 | 0.45 0.04 to 11.42 | 0.40 0.03 to 11.37 |
| OTHER_ACTIVE_basal_bolus_insulin | 4.67 0.74 to 32.58 | 45.77 3.61 to 846 | 12.93 0.14 to 1454 | 10.45 0.27 to 422 | 9.07 0.09 to 1239 | 8.13 0.18 to 382 | 7.23 1.15 to 52.95 | 2.88 1.29 to 6.95 | 2.50 0.39 to 18.28 | 2.37 0.41 to 16.43 | 2.17 0.32 to 17.83 | 1.92 0.24 to 16.48 | 1.92 0.24 to 17.63 | 1.90 0.27 to 14.78 | 1.80 0.25 to 15.72 | 1.64 0.26 to 11.79 | 1.52 0.03 to 48.88 | 1.35 0.18 to 12.00 | 1.22 0.20 to 8.68 | 1.21 0.20 to 8.48 | 1.06 0.14 to 8.47 | 0.95 0.03 to 19.74 | OTHER_ACTIVE_basal_bolus_insulin | 0.98 0.12 to 8.47 | 0.94 0.15 to 6.95 | 0.45 0.06 to 3.46 | 0.38 0.04 to 4.38 |
| INS_ASPART | 4.75 1.59 to 13.85 | 45.25 5.47 to 539 | 12.49 0.18 to 1174 | 10.31 0.34 to 271 | 9.02 0.11 to 1032 | 8.14 0.25 to 237 | 7.49 2.30 to 22.36 | 2.96 0.31 to 25.78 | 2.56 0.73 to 8.13 | 2.44 0.86 to 6.67 | 2.27 0.76 to 6.42 | 1.94 0.47 to 7.76 | 1.97 1.31 to 3.02 | 1.93 0.97 to 3.92 | 1.85 0.76 to 4.48 | 1.70 0.52 to 5.17 | 1.56 0.04 to 30.62 | 1.40 0.51 to 3.68 | 1.26 0.41 to 3.62 | 1.25 0.42 to 3.54 | 1.08 0.34 to 3.41 | 1.02 0.04 to 11.78 | 1.02 0.12 to 8.05 | INS_ASPART | 0.98 0.29 to 3.03 | 0.45 0.16 to 1.30 | 0.40 0.07 to 2.09 |
| INS_LISPRO | 4.89 2.43 to 10.28 | 45.59 7.21 to 484 | 13.05 0.21 to 1048 | 10.48 0.42 to 274 | 9.46 0.13 to 1052 | 8.55 0.28 to 241 | 7.57 3.93 to 16.53 | 3.06 0.37 to 23.11 | 2.66 1.68 to 3.72 | 2.48 1.45 to 4.92 | 2.30 0.82 to 6.65 | 2.03 0.62 to 6.12 | 2.01 0.62 to 7.41 | 1.97 0.78 to 5.59 | 1.89 0.67 to 6.21 | 1.73 1.21 to 2.72 | 1.59 0.04 to 29.36 | 1.43 0.46 to 4.75 | 1.27 0.75 to 2.52 | 1.27 0.76 to 2.41 | 1.10 0.38 to 3.41 | 1.05 0.04 to 10.57 | 1.06 0.14 to 6.74 | 1.02 0.33 to 3.50 | INS_LISPRO | 0.47 0.18 to 1.28 | 0.40 0.07 to 2.01 |
| GLIMEPIRIDE | 10.47 4.25 to 26.79 | 98.91 13.65 to 1078 | 27.43 0.40 to 2546 | 22.60 0.83 to 609 | 19.69 0.25 to 2242 | 17.96 0.57 to 548 | 16.24 6.35 to 42.08 | 6.53 0.75 to 54.03 | 5.64 1.97 to 15.08 | 5.35 2.41 to 12.29 | 4.94 1.79 to 14.13 | 4.31 1.18 to 15.10 | 4.31 1.40 to 13.66 | 4.23 1.96 to 9.76 | 4.03 1.59 to 11.23 | 3.73 1.47 to 9.55 | 3.48 0.09 to 68.13 | 3.07 1.08 to 9.02 | 2.74 1.16 to 6.67 | 2.74 1.20 to 6.54 | 2.36 1.57 to 3.81 | 2.24 0.09 to 23.64 | 2.24 0.29 to 15.79 | 2.21 0.77 to 6.33 | 2.13 0.78 to 5.66 | GLIMEPIRIDE | 0.87 0.20 to 3.21 |
| INS_PREMIX | 12.19 2.63 to 61.77 | 115 11.04 to 1673 | 32.19 0.38 to 3465 | 26.38 0.79 to 880 | 23.45 0.24 to 3257 | 20.66 0.55 to 774 | 18.96 3.82 to 103 | 7.71 0.64 to 91.92 | 6.54 1.22 to 35.07 | 6.19 1.42 to 31.56 | 5.69 1.14 to 32.09 | 4.99 0.82 to 31.63 | 5.03 0.92 to 30.92 | 4.91 1.11 to 25.46 | 4.73 0.93 to 27.11 | 4.31 0.89 to 22.89 | 4.01 0.09 to 107 | 3.56 0.69 to 20.82 | 3.19 0.70 to 16.41 | 3.19 0.71 to 16.22 | 2.71 0.81 to 11.11 | 2.53 0.09 to 39.88 | 2.62 0.23 to 27.45 | 2.53 0.48 to 14.83 | 2.48 0.50 to 13.34 | 1.14 0.31 to 5.03 | INS_PREMIX |
Heterogeneity, fit and convergence
Bayesian random effects (primary)
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.
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 | Baseline HbA1c (percent) effect modifier, prognostic factor; 38 of 38 | Background glucose lowering therapy (stratum S0 to S4) effect modifier, prognostic factor; 35 of 38 |
|---|---|---|
| ELEGANT S001780 | 7.34 | S4 |
| NCT02229227 S001887 | 7.7 | S3 |
| LIXILAN JP-O1 S002018 | 8.39 | S1 |
| NCT03131687 S000010 | 8.13 | S1 |
| NCT00838916 S000099 | 8.31 | S1 |
| SURPASS-6 S000108 | 8.8 | S2 |
| Lixilan-O-AP S000170 | 8.34 | S1 |
| NCT01476475 S000191 | 8.05 | S1 |
| NCT02846233 S000236 | 9.99 | S3 |
| AWARD-7 S000237 | 8.6 | S3 |
| NCT01584232 S000246 | 8.05 | S1 |
| NCT04235959 S000277 | 7.92 | S0 |
| SUSTAIN 11 S000363 | 8.55 | S2 |
| LIRA-PRIME S000508 | 8.15 | S1 |
| NCT02081118 S000719 | 7.9 | S1 |
| EXENDA S000796 | 7.57 | S1 |
| NCT01558271 S000837 | 8.14 | S0 |
| NCT02200991 S001003 | 8.29 | S2 |
| AWARD-CHN1 S001064 | 7.97 | S0 |
| AWARD-8 S001068 | 8.4 | S1 |
| NCT00359762 S001097 | 7.45 | S1 |
| NCT02449603 S001146 | 8.78 | S1 |
| NCT03985293 S001191 | 8.08 | S1 |
| LixiLan-O S001199 | 8.1 | S1 |
| SOLID-DKD S001370 | 7.61 | S4 |
| AWARD-CHN2 S001404 | 8.37 | S1 |
| LixiLan-L S001409 | 8.08 | S2 |
| Lixilan-L-CN S002110 | 8.3 | S2 |
| NCT01425580 S002231 | 13.83 median | S1 |
| SIMPLE S002252 | 12.05 | S2 |
| NCT03311724 S002256 | 8.38 | S1 |
| BEYOND S002277 | 8.57 | S3 |
| LIXILAN JP-O2 S002305 | 8.04 | S1 |
| NCT06256523 S002776 | 8.12 | not reported |
| S002928 S002928 | 7.3 median | S1 |
| S002951 S002951 | 8.75 | not reported |
| S003090 S003090 | 8.1 | S3 |
| S003152 S003152 | 8.86 | 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.
- FlagEligibility, bmi entry range: a design requires bmi 50 or more while another admits only 35 or less
- FlagBaseline, Baseline HbA1c: design means range from 7.3 (PEGLOX_SC vs PLACEBO) to 13.8 (GLIMEPIRIDE vs LIRA_SC) percent; threshold 0.5
- FlagEligibility, hba1c entry range: a design requires hba1c 45 or more while another admits only 8.5 or less
- NoteOutcome assessment, time point: selected time points span 1 to 156.54 weeks
- NoteOutcome assessment, analysis set: mixed: completers 1, full_analysis 1, modified_itt 4, other 3, randomized 3, safety 26
- NoteOutcome assessment, definition: mixed: any hypoglycemia, blood glucose below 70 mg/dL 1, documented asymptomatic hypoglycemia, glucose below 3.9 mmol/L 1, documented below 3.0 mmol/L regardless of symptoms (ADA level 2) 1, documented plasma glucose below 3.0 mmol/L regardless of symptoms 1, documented symptomatic hypoglycemia, plasma glucose 70 mg/dL or less 1, documented symptomatic, glucose 3.9 mmol/L or less with symptoms 1, documented symptomatic, plasma glucose 3.9 mmol/L or less 1, Documented symptomatic, plasma glucose 3.9 mmol/L or lower 1, glucose below 54 mg/dL or severe hypoglycemia 1, Grade 1 or 2 hypoglycemia below 3.9 mmol/L 1, hypoglycemia AE with BG 3.9 mmol/L or lower 1, hypoglycemia below 3.0 mmol/L or requiring assistance 1, hypoglycemia glucose 3.9 mmol/L or lower; both events mild 1, level 1, below 70 mg/dL with symptoms or signs 1, level 3 severe hypoglycemia 1, not stated 7, participants whose worst on therapy event had glucose below 3.1 mmol/L 1, patients with any glucose below 70 mg/dL 1, plasma glucose 54 mg/dL or lower 1, protocol defined severe hypoglycemia 1, severe hypoglycemia needing assistance of another person 2, severe hypoglycemia needing resuscitative help, before rescue 1, severe hypoglycemia needing third party assistance 1, severe hypoglycemia requiring assistance from another person 1, Severe hypoglycemia, impaired consciousness or not self managed 1, severe or BG confirmed symptomatic below 3.1 mmol/L 1, severe symptomatic hypoglycemia requiring third party assistance 1, severe, assistance of another person required 1, severe, needing assistance of another person 1, severe, requiring assistance of another person 1, total hypoglycemia, plasma glucose 70 mg/dL or less 1
- NoteOutcome assessment, proportion method: mixed: not stated 35, observed 3
- NoteOutcome assessment, intercurrent events (discontinuation): mixed: hypothetical 1, not stated 36, while_on_treatment 1
- NoteOutcome assessment, intercurrent events (rescue): mixed: hypothetical 5, not stated 33
- NoteRisk of bias, blinding: mixed: double_blind 11, open_label 24, single_blind 3
- NoteRisk of bias, funding: mixed: industry 30, mixed 2, non_industry 5, not_reported 1
- NoteData handling, input conversions: arms_combined 10, count_from_percent 8, printed_denominator 7
| Trial | time weeks | blinding | analysis set | definition | instrument | adjudicated | proportion method | intercurrent events (discontinuation) | intercurrent events (rescue) | funding | start year | Eligibility |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ELEGANT | 26 | open_label | randomized | Grade 1 or 2 hypoglycemia below 3.9 mmol/L | not stated | not stated | not stated | not stated | not stated | industry | 2012 | age 18 to 75; BMI 25 or more; HbA1c 6.5 to 8.5 percent; insulin 3 to 16 months with 4 percent weight gain |
| NCT02229227 | 26 | open_label | safety | participants whose worst on therapy event had glucose below 3.1 mmol/L | not stated | not stated | not stated | not stated | not stated | industry | 2014 | age 18 to 75; HbA1c 7.0 to 9.5 percent at screening; BMI 40 or less; basal plus prandial insulin |
| LIXILAN JP-O1 | 52.14 | open_label | safety | severe hypoglycemia requiring assistance from another person | not stated | not stated | not stated | not stated | not stated | industry | 2016 | insulin naive Japanese adults; HbA1c 7.5 to 10%; FPG 13.8 mmol/L or less; one or two OADs |
| NCT03131687 | 30 | double_blind | safety | severe hypoglycemia needing assistance of another person | not stated | not stated | not stated | not stated | not stated | 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 |
| NCT00838916 | 52 | open_label | safety | severe hypoglycemia needing resuscitative help, before rescue | not stated | not stated | not stated | not stated | hypothetical | industry | 2009 | age 18 or older, HbA1c 7.0 to 10.0 percent, BMI 20 to 45, creatinine clearance above 60 |
| SURPASS-6 | 56 | open_label | safety | glucose below 54 mg/dL or severe hypoglycemia | not stated | not stated | not stated | while_on_treatment | hypothetical | industry | 2020 | adults 18 or older; HbA1c 7.5 to 11 percent; BMI 23 to 45; basal insulin at least 30 U/day with or without up to 2 oral drugs |
| Lixilan-O-AP | 24.43 | open_label | safety | documented plasma glucose below 3.0 mmol/L regardless of symptoms | not stated | not stated | not stated | not stated | not stated | industry | 2019 | adults with T2D on metformin with or without a second OAD; HbA1c 7.5 to 11 percent, or 7 to 10 percent with a non SGLT2i second OAD |
| NCT01476475 | 24 | open_label | safety | Documented symptomatic, plasma glucose 3.9 mmol/L or lower | not stated | not stated | not stated | not stated | not stated | industry | 2011 | Adults with T2D; HbA1c 7 to 10 percent on metformin at least 1.5 g/day; insulin naive |
| NCT02846233 | 16 | open_label | randomized | any hypoglycemia, blood glucose below 70 mg/dL | not stated | not stated | not stated | not stated | not stated | non_industry | 2016 | age over 21; BMI 30 or more; HbA1c above 8 percent; eGFR above 45; basal plus prandial or premixed insulin |
| AWARD-7 | 52 | single_blind | safety | total hypoglycemia, plasma glucose 70 mg/dL or less | not stated | not stated | not stated | hypothetical | hypothetical | industry | 2012 | adults with T2D and CKD stage 3 to 4 (eGFR 15 to below 60); HbA1c 7.5 to 10.5 percent on insulin; maximal ACEI or ARB; BMI 23 to 45 |
| NCT01584232 | 26 | open_label | safety | severe, needing assistance of another person | not stated | not stated | not stated | not stated | hypothetical | 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 |
| NCT04235959 | 28 | double_blind | safety | hypoglycemia glucose 3.9 mmol/L or lower; both events mild | not stated | not stated | not stated | not stated | not stated | industry | 2020 | Chinese adults 20 to 70 years, HbA1c 7.0 to 10.5 diet only or 6.5 to 10.0 on one OAM, BMI 23 or more |
| SUSTAIN 11 | 52 | open_label | full_analysis | not stated | not stated | not stated | not stated | not stated | not stated | industry | 2018 | adults; HbA1c above 7.5 to 10.0 percent on insulin glargine plus metformin |
| LIRA-PRIME | 104 | open_label | safety | severe or BG confirmed symptomatic below 3.1 mmol/L | not stated | not stated | not stated | not stated | not stated | industry | 2016 | adults; HbA1c 7.5 to 9.0 percent; stable metformin monotherapy |
| NCT02081118 | 22 | double_blind | safety | hypoglycemia AE with BG 3.9 mmol/L or lower | not stated | not stated | not stated | not stated | not stated | industry | 2014 | age 18 to under 75; metformin; HbA1c 7.0 to 10 percent; BMI under 40 |
| EXENDA | 28 | double_blind | randomized | not stated | not stated | not stated | not stated | not stated | not stated | industry | 2017 | age 18 to 75; BMI 25 or more; HbA1c 6.5 to 11 percent; metformin 1000 mg or more |
| NCT01558271 | 26 | double_blind | safety | severe, assistance of another person required | not stated | not stated | not stated | not stated | not stated | industry | 2012 | Japanese; age 20 or more; BMI 18.5 to 35; HbA1c 7.0 to 10.0 percent; OAM naive or OAM stopped |
| NCT02200991 | 4.43 | open_label | safety | severe hypoglycemia needing third party assistance | not stated | not stated | not stated | not stated | not stated | industry | 2014 | age 20 to 75; T2D 5 years or more; HbA1c 7.0 to 10.0; FBG 180 mg/dL or less; stable glargine |
| AWARD-CHN1 | 26 | double_blind | safety | severe, requiring assistance of another person | not stated | not stated | not stated | not stated | not stated | industry | 2012 | age 18 or older; BMI 19 to 35 kg/m2; HbA1c 7.0 to 10.5 percent OAM naive or 6.5 to 10.0 percent on OAM monotherapy |
| AWARD-8 | 24 | double_blind | modified_itt | severe hypoglycemia needing assistance of another person | not stated | not stated | not stated | not stated | hypothetical | industry | 2013 | age 18 or older; BMI up to 45; HbA1c 7.5 to 9.5 percent on sulfonylurea at least half maximal dose |
| NCT00359762 | 156.54 | open_label | safety | documented asymptomatic hypoglycemia, glucose below 3.9 mmol/L | not stated | not stated | not stated | not stated | not stated | industry | 2006 | age 18 to 85; BMI 25 to below 40; HbA1c 6.5 to below 9.0 percent on maximum tolerated metformin |
| NCT02449603 | 16 | open_label | safety | not stated | not stated | not stated | not stated | not stated | not stated | mixed | 2015 | age 18 to 70, HbA1c 7.5 to 10.0 percent on metformin at least 1500 mg, BMI 21 to 35 |
| NCT03985293 | 20 | double_blind | safety | protocol defined severe hypoglycemia | not stated | not stated | not stated | not stated | not stated | industry | 2019 | age 18 to 75; HbA1c 7 to 10.5 percent; BMI 22.5 (Asia) or 24.5 to 45.4; metformin or diet and exercise |
| LixiLan-O | 30.14 | open_label | safety | documented symptomatic, plasma glucose 3.9 mmol/L or less | not stated | not stated | not stated | not stated | not stated | industry | 2014 | adults; HbA1c 7.5 to 10% on metformin or 7 to 9% on metformin plus second OAD; 7 to 10% after run in |
| SOLID-DKD | 18 | double_blind | safety | level 3 severe hypoglycemia | not stated | not stated | not stated | not stated | not stated | industry | 2024 | age 18 to 75; T2D with UACR 300 to below 3000 mg/g; eGFR 30 or more; HbA1c 6.5 to 10; BMI 20 to 40 |
| AWARD-CHN2 | 52 | open_label | safety | documented symptomatic, glucose 3.9 mmol/L or less with symptoms | not stated | not stated | not stated | not stated | not stated | industry | 2012 | age 18 or older; BMI 19 to 35 kg/m2; HbA1c 7.0 to 11.0 percent on metformin and/or sulfonylurea |
| LixiLan-L | 30 | open_label | safety | severe symptomatic hypoglycemia requiring third party assistance | not stated | not stated | not stated | not stated | not stated | industry | 2014 | adults with T2D on basal insulin 15 to 40 U/d; HbA1c 7 to 10% and glargine 20 to 50 U after run in |
| Lixilan-L-CN | 30 | open_label | safety | documented below 3.0 mmol/L regardless of symptoms (ADA level 2) | not stated | not stated | not stated | not stated | not stated | industry | 2019 | Chinese adults; HbA1c 7.0 to 10.5 percent; basal insulin 10 to 25 U/day with up to 2 oral drugs; FPG at most 8.9 mmol/L |
| NCT01425580 | 18 | single_blind | other | not stated | not stated | not stated | not stated | not stated | not stated | mixed | 2012 | type 2 diabetes; HbA1c 45 to 97 mmol/mol; subclinical LV dysfunction on echocardiography; BMI 40 or less |
| SIMPLE | 26 | open_label | completers | not stated | not stated | not stated | observed | not stated | not stated | industry | 2014 | age 18 or older; HbA1c 10 or higher; no prandial insulin, DPP-4 inhibitor or GLP-1 RA |
| NCT03311724 | 16 | double_blind | modified_itt | plasma glucose 54 mg/dL or lower | not stated | not stated | not stated | not stated | not stated | industry | 2017 | age 18 to 75; T2D at least 6 months; HbA1c 7.0 to 10.5%; BMI 23 to 45; diet or stable metformin |
| BEYOND | 104.28 | open_label | other | level 1, below 70 mg/dL with symptoms or signs | not stated | not stated | observed | not stated | not stated | non_industry | 2019 | age over 35; HbA1c above 7.5 percent; basal bolus insulin 6 months or more; eGFR 60 or more |
| LIXILAN JP-O2 | 26 | open_label | modified_itt | documented symptomatic hypoglycemia, plasma glucose 70 mg/dL or less | not stated | not stated | observed | not stated | not stated | industry | 2016 | HbA1c 7.5 to 9.5 percent; FPG 10.0 mmol/L or less; up to two OADs or three with DPP4i |
| NCT06256523 | 29 | double_blind | safety | not stated | not stated | not stated | not stated | not stated | not stated | industry | 2022 | age 18 to 65; HbA1c 7.0 to 10.0 percent; BMI 18.5 to 35; eGFR 60 or more |
| S002928 | 24 | single_blind | safety | hypoglycemia below 3.0 mmol/L or requiring assistance | not stated | not stated | not stated | not stated | not stated | non_industry | 2022 | age 18 to 65; BMI 50 or more; type 2 diabetes |
| S002951 | 16 | open_label | safety | not stated | not stated | not stated | not stated | not stated | not stated | non_industry | 2022 | age 18 to 65; BMI 25 or more; HbA1c 7.0 to 10.0 percent; lifestyle or one OAD |
| S003090 | 1 | open_label | modified_itt | patients with any glucose below 70 mg/dL | not stated | not stated | not stated | not stated | not stated | not_reported | age over 18; type 2 diabetes over 3 months; noncritical inpatients; prior insulin under 10 units/day | |
| S003152 | 24 | open_label | other | Severe hypoglycemia, impaired consciousness or not self managed | not stated | not stated | not stated | not stated | not stated | non_industry | 2019 | age 18 or more; BMI 24 or more; HbA1c 7.0 percent or more; metformin 1500 mg/d or more alone or with premixed insulin |
Trial data
What each trial contributes. Arm rows give the arm value with its standard error, or events over participants; contrast rows give the hazard ratio (from event counts) on the analysis scale (log) against the trial's first row. Flags mark converted, combined or approximated inputs.
| Trial | Arm | Treatment | Week | Data | Value | SE | Events / N | Flags | Source |
|---|---|---|---|---|---|---|---|---|---|
| NCT03131687 | A1 | PLACEBO | 30 | arm, events | 2 / 51 | R0016215:Table 3 | |||
| NCT03131687 | A2+A3+A4+A5 | TIRZ_SC | 30 | arm, events | 14 / 213 | arms_combined | R0016215:Table 3 | ||
| NCT03131687 | A6 | DULA_SC | 30 | arm, events | 2 / 54 | R0016215:Table 3 | |||
| NCT00838916 | A1 | ALBI_SC | 52 | arm, events | 88 / 516 | R0025374:Table 3 | |||
| NCT00838916 | A2 | INS_GLARGINE | 52 | arm, events | 66 / 263 | R0025374:Table 3 | |||
| SURPASS-6 | A1+A2+A3 | TIRZ_SC | 56 | arm, events | 263 / 717 | arms_combined | R0009666:Table 4 | ||
| SURPASS-6 | A4 | INS_LISPRO | 56 | arm, events | 519 / 711 | R0009666:Table 4 | |||
| Lixilan-O-AP | A1 | IGLARLIXI_SC | 24.43 | arm, events | 171 / 351 | R0013321:Table 3 | |||
| Lixilan-O-AP | A2 | INS_GLARGINE | 24.43 | arm, events | 161 / 350 | R0013321:Table 3 | |||
| Lixilan-O-AP | A3 | LIXI_SC | 24.43 | arm, events | 12 / 177 | R0013321:Table 3 | |||
| NCT01476475 | A1 | IGLARLIXI_SC | 24 | arm, events | 35 / 161 | R0021236:Table 2 | |||
| NCT01476475 | A2 | INS_GLARGINE | 24 | arm, events | 37 / 162 | R0021236:Table 2 | |||
| NCT02846233 | A1 | DULA_SC | 16 | arm, events | 1 / 12 | R0028441:Table 5 | |||
| NCT02846233 | A2 | OTHER_ACTIVE_basal_bolus_insulin | 16 | arm, events | 3 / 10 | R0028441:Table 5 | |||
| AWARD-7 | A1 | INS_GLARGINE | 52 | arm, events | 145 / 194 | R0017387:Supplement Table 12 | |||
| AWARD-7 | A2+A3 | DULA_SC | 52 | arm, events | 208 / 383 | arms_combined | R0017387:Supplement Table 12 | ||
| NCT01584232 | A1 | DULA_SC | 26 | arm, events | 47 / 181 | R0016159:Results | |||
| NCT01584232 | A2 | INS_GLARGINE | 26 | arm, events | 86 / 180 | R0016159:Results | |||
| NCT04235959 | A1 | PLACEBO | 28 | arm, events | 0 / 4 | R0019570:Table 2 | |||
| NCT04235959 | A3 | TIRZ_SC | 28 | arm, events | 1 / 10 | R0019570:Table 2 | |||
| SUSTAIN 11 | A1 | SEMA_SC | 52 | arm, events | 330 / 874 | R0022346:Table 2 | |||
| SUSTAIN 11 | A2 | INS_ASPART | 52 | arm, events | 528 / 874 | R0022346:Table 2 | |||
| LIRA-PRIME | A1 | LIRA_SC | 104 | arm, events | 50 / 996 | R0022482:Supplement Table S5 | |||
| LIRA-PRIME | A2 | OTHER_ACTIVE_investigator_choice_oral_drug | 104 | arm, events | 53 / 995 | R0022482:Supplement Table S5 | |||
| NCT02081118 | A1 | PLACEBO | 22 | arm, events | 0 / 51 | R0009733:Results | |||
| NCT02081118 | A2+A3+A4 | EFPE_SC | 22 | arm, events | 0 / 157 | printed_denominator;arms_combined | R0009733:Results | ||
| EXENDA | A1 | EXENER_SC | 28 | arm, events | 0 / 16 | R0025594:Results | |||
| EXENDA | A2 | PLACEBO | 28 | arm, events | 0 / 14 | R0025594:Results | |||
| NCT01558271 | A1 | DULA_SC | 26 | arm, events | 6 / 281 | R0011901:Results | |||
| NCT01558271 | A2 | LIRA_SC | 26 | arm, events | 2 / 141 | R0011901:Results | |||
| NCT01558271 | A3 | PLACEBO | 26 | arm, events | 1 / 70 | R0011901:Results | |||
| NCT02200991 | A1 | LIXI_SC | 4.43 | arm, events | 7 / 69 | R0024589:Table 3 | |||
| NCT02200991 | A2 | SITAGLIPTIN | 4.43 | arm, events | 1 / 67 | R0024589:Table 3 | |||
| AWARD-CHN1 | A1+A2 | DULA_SC | 26 | arm, events | 4 / 492 | arms_combined | R0014229:Table 2 | ||
| AWARD-CHN1 | A3 | GLIMEPIRIDE | 26 | arm, events | 15 / 245 | R0014229:Table 2 | |||
| AWARD-8 | A1 | DULA_SC | 24 | arm, events | 50 / 240 | R0016038:Table 3 | |||
| AWARD-8 | A2 | PLACEBO | 24 | arm, events | 2 / 60 | R0016038:Table 3 | |||
| NCT00359762 | A1 | EXEN_SC | 156.54 | arm, events | 122 / 515 | R0016082:Results | |||
| NCT00359762 | A2 | GLIMEPIRIDE | 156.54 | arm, events | 237 / 514 | R0016082:Results | |||
| NCT02449603 | A1 | EXEN_SC | 16 | arm, events | 3 / 52 | count_from_percent;printed_denominator | R0023224:Abstract | ||
| NCT02449603 | A2 | INS_PREMIX | 16 | arm, events | 9 / 52 | count_from_percent;printed_denominator | R0023224:Abstract | ||
| NCT03985293 | A1 | PLACEBO | 20 | arm, events | 0 / 66 | R0006095:Supplement eTable 1 | |||
| NCT03985293 | A2+A3+A4+A5+A6 | DANU_PO | 20 | arm, events | 7 / 346 | arms_combined | R0006095:Supplement eTable 1 | ||
| LixiLan-O | A1 | IGLARLIXI_SC | 30.14 | arm, events | 120 / 469 | R0013783:Supplement Table S2 | |||
| LixiLan-O | A2 | INS_GLARGINE | 30.14 | arm, events | 110 / 467 | R0013783:Supplement Table S2 | |||
| LixiLan-O | A3 | LIXI_SC | 30.14 | arm, events | 15 / 234 | R0013783:Supplement Table S2 | |||
| SOLID-DKD | A1+A2 | HRS7535_PO | 18 | arm, events | 32 / 187 | arms_combined | R0004355:Table 2 | ||
| SOLID-DKD | A3 | PLACEBO | 18 | arm, events | 7 / 94 | R0004355:Table 2 | |||
| AWARD-CHN2 | A1+A2 | DULA_SC | 52 | arm, events | 57 / 515 | arms_combined | R0023722:Supplement Table S7 | ||
| AWARD-CHN2 | A3 | INS_GLARGINE | 52 | arm, events | 52 / 259 | R0023722:Supplement Table S7 | |||
| LixiLan-L | A1 | IGLARLIXI_SC | 30 | arm, events | 146 / 367 | R0014829:Table 3 | |||
| LixiLan-L | A2 | INS_GLARGINE | 30 | arm, events | 155 / 369 | R0014829:Table 3 | |||
| ELEGANT | A1 | LIRA_SC | 26 | arm, events | 15 / 26 | R0025175:Table 3 | |||
| ELEGANT | A2 | STANDARD_CARE | 26 | arm, events | 8 / 24 | R0025175:Table 3 | |||
| NCT02229227 | A1 | ALBI_SC | 26 | arm, events | 290 / 402 | R0008089:Table 3 | |||
| NCT02229227 | A2 | INS_LISPRO | 26 | arm, events | 359 / 412 | R0008089:Table 3 | |||
| LIXILAN JP-O1 | A1 | IGLARLIXI_SC | 52.14 | arm, events | 29 / 161 | R0015751:Table 3 | |||
| LIXILAN JP-O1 | A2 | LIXI_SC | 52.14 | arm, events | 7 / 160 | R0015751:Table 3 | |||
| Lixilan-L-CN | A1 | IGLARLIXI_SC | 30 | arm, events | 141 / 212 | R0014540:Supplement Table S4 | |||
| Lixilan-L-CN | A2 | INS_GLARGINE | 30 | arm, events | 152 / 214 | R0014540:Supplement Table S4 | |||
| NCT01425580 | A1 | LIRA_SC | 18 | arm, events | 6 / 33 | R0025885:Results | |||
| NCT01425580 | A2 | GLIMEPIRIDE | 18 | arm, events | 17 / 29 | R0025885:Results | |||
| SIMPLE | A1 | INS_ASPART | 26 | arm, events | 29 / 61 | count_from_percent | registry:outcomes | ||
| SIMPLE | A2 | LIRA_SC | 26 | arm, events | 16 / 59 | count_from_percent | registry:outcomes | ||
| NCT03311724 | A1 | PLACEBO | 16 | arm, events | 0 / 26 | R0010282:Table 2 | |||
| NCT03311724 | A2+A3+A4 | TIRZ_SC | 16 | arm, events | 12 / 85 | arms_combined | R0010282:Table 2 | ||
| BEYOND | A1 | OTHER_ACTIVE_basal_bolus_insulin | 104.28 | arm, events | 25 / 101 | count_from_percent | R0022468:Results | ||
| BEYOND | A3 | OTHER_ACTIVE_basal_insulin_sglt2i | 104.28 | arm, events | 10 / 102 | count_from_percent | R0022468:Results | ||
| LIXILAN JP-O2 | A1 | IGLARLIXI_SC | 26 | arm, events | 37 / 260 | count_from_percent | R0009500:Results | ||
| LIXILAN JP-O2 | A2 | INS_GLARGINE | 26 | arm, events | 32 / 261 | count_from_percent | R0009500:Results | ||
| NCT06256523 | A1 | BOFANG_SC | 29 | arm, events | 2 / 27 | printed_denominator | R0002476:Table 2 | ||
| NCT06256523 | A2 | PLACEBO | 29 | arm, events | 0 / 9 | printed_denominator | R0002476:Table 2 | ||
| S002928 | A1 | PLACEBO | 24 | arm, events | 0 / 41 | R0007034:Table 4 | |||
| S002928 | A2+A3 | PEGLOX_SC | 24 | arm, events | 0 / 82 | arms_combined | R0007034:Table 4 | ||
| S002951 | A1 | PEGLOX_SC | 16 | arm, events | 3 / 104 | R0007588:Table 3 | |||
| S002951 | A2 | METFORMIN | 16 | arm, events | 2 / 52 | R0007588:Table 3 | |||
| S003090 | A1 | STANDARD_CARE | 1 | arm, events | 9 / 27 | printed_denominator | R0025350:Table 3 | ||
| S003090 | A2 | DULA_SC | 1 | arm, events | 3 / 27 | printed_denominator | R0025350:Table 3 | ||
| S003152 | A1 | LIRA_SC | 24 | arm, events | 21 / 180 | R0022648:Results | |||
| S003152 | A2 | DAPAGLIFLOZIN | 24 | arm, events | 29 / 180 | R0022648:Results |
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