Network meta-analysis

Acute kidney injury

Type 2 diabetes (adults)

longest follow-upRecorded harmsEach dose separatelyHazard ratio (from event counts)

Randomized trials

Treatments

8,758

Participants

Events

In plain language

Across 16 trials with 8,758 participants, 0 of 33 treatments had a clearly better result than placebo on acute kidney injury, 1 a clearly worse one, and for 32 the evidence could not tell them apart from placebo. The most favorable estimate was for HRS-7535 90 mg tablet once daily: hazard ratio (from event counts) 0.19 (95% credible interval 0.00 to 4.44).

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.

Node area shows participants; line width shows trials comparing two treatments directly. Blue: GLP-1 receptor agonist containing treatments; grey: comparators. Hover over or tab to a node or line for details.

Effects compared with Placebo

Hazard ratio (from event counts). Lower values favor the treatment.

Versus Placebo, log scale. Blue: Bayesian random effects posterior median with 95% credible interval (thick) and 95% prediction interval (dashed). Amber diamond: frequentist estimate with 95% confidence interval. Hover over or tab to a row for its values.

Effects of each treatment versus Placebo
Treatment	Bayesian HR (95% CrI)	95% prediction interval	Verdict
HRS-7535 90 mg tablet once daily HRS7535_PO_90MG_QD	0.19 (0.00 to 4.44)	0.00 to 5.23	Unclear
Orforglipron 12 mg oral once daily ORFO_PO_12MG_QD	0.24 (0.00 to 6.13)	0.00 to 7.05	Unclear
Semaglutide 16 mg injection once weekly SEMA_SC_16MG_QW	0.25 (0.00 to 7.83)	0.00 to 9.08	Unclear
Semaglutide 2.0 mg subcutaneous once weekly SEMA_SC_2p0MG_QW	0.26 (0.00 to 8.04)	0.00 to 8.94	Unclear
Semaglutide 8 mg injection once weekly SEMA_SC_8MG_QW	0.27 (0.00 to 7.76)	0.00 to 8.97	Unclear
Exenatide 10 ug subcutaneous twice daily EXEN_SC_10UG_BID	0.31 (0.00 to 16.10)	0.00 to 17.92	Unclear
Semaglutide 3 mg oral once daily (original tablet) SEMA_PO_3MG_QD	0.38 (0.03 to 4.21)	0.02 to 5.02	Unclear
Semaglutide 7 mg oral once daily (original tablet) SEMA_PO_7MG_QD	0.39 (0.02 to 4.14)	0.02 to 5.00	Unclear
Efpeglenatide 6 mg subcutaneous once weekly EFPE_SC_6MG_QW	0.39 (0.01 to 18.10)	0.00 to 19.58	Unclear
Efpeglenatide 2 mg subcutaneous once weekly EFPE_SC_2MG_QW	0.41 (0.01 to 17.05)	0.00 to 19.06	Unclear
Lotiglipron 260 mg tablet once daily LOTI_PO_260MG_QD	0.46 (0.01 to 15.95)	0.01 to 18.06	Unclear
Loti po 200mg qd LOTI_PO_200MG_QD	0.46 (0.01 to 17.92)	0.00 to 21.58	Unclear
Lotiglipron 80 mg tablet once daily LOTI_PO_80MG_QD	0.46 (0.01 to 17.65)	0.00 to 21.77	Unclear
Sitagliptin SITAGLIPTIN	0.49 (0.03 to 6.48)	0.02 to 7.87	Unclear
Standard care or no added treatment STANDARD_CARE	0.51 (0.01 to 40.24)	0.00 to 43.32	Unclear
Lotiglipron 160 mg tablet once daily LOTI_PO_160MG_QD	0.54 (0.01 to 25.70)	0.01 to 29.02	Unclear
Lotiglipron 140 mg tablet once daily LOTI_PO_140MG_QD	0.56 (0.01 to 27.68)	0.01 to 29.83	Unclear
Dulaglutide 4.5 mg subcutaneous once weekly DULA_SC_4p5MG_QW	0.57 (0.04 to 9.49)	0.03 to 10.80	Unclear
Dulaglutide 0.75 mg subcutaneous once weekly DULA_SC_0p75MG_QW	0.58 (0.01 to 38.31)	0.01 to 40.35	Unclear
Lotiglipron 20 mg tablet once daily LOTI_PO_20MG_QD	0.59 (0.01 to 23.73)	0.01 to 28.52	Unclear
Semaglutide 14 mg oral once daily (original tablet) SEMA_PO_14MG_QD	0.61 (0.06 to 4.89)	0.05 to 5.87	Unclear
Exenatide 5 ug subcutaneous twice daily EXEN_SC_5UG_BID	0.65 (0.01 to 53.05)	0.01 to 63.28	Unclear
Dulaglutide 1.5 mg subcutaneous once weekly DULA_SC_1p5MG_QW	0.69 (0.04 to 10.80)	0.04 to 13.33	Unclear
Mazdutide 4.5 mg subcutaneous once weekly MAZD_SC_4p5MG_QW	0.69 (0.01 to 52.19)	0.01 to 56.26	Unclear
Dulaglutide 3.0 mg subcutaneous once weekly DULA_SC_3p0MG_QW	0.70 (0.04 to 10.93)	0.04 to 13.01	Unclear
Mazdutide 3 mg subcutaneous once weekly MAZD_SC_3MG_QW	0.70 (0.01 to 52.88)	0.01 to 56.60	Unclear
HRS-7535 30 mg tablet once daily HRS7535_PO_30MG_QD	1.13 (0.07 to 16.41)	0.06 to 20.75	Unclear
Orforglipron 3 mg oral once daily ORFO_PO_3MG_QD	1.59 (0.08 to 24.33)	0.07 to 28.26	Unclear
Exenatide extended release 2 mg subcutaneous once weekly EXENER_SC_2MG_QW	2.51 (0.10 to 76.21)	0.09 to 89.41	Unclear
Liraglutide 1.8 mg subcutaneous once daily LIRA_SC_1p8MG_QD	2.83 (0.10 to 72.03)	0.08 to 79.19	Unclear
Orforglipron 36 mg oral once daily ORFO_PO_36MG_QD	3.77 (0.31 to 50.02)	0.27 to 59.12	Unclear
Efpeglenatide 4 mg subcutaneous once weekly EFPE_SC_4MG_QW	4.60 (0.18 to 136)	0.15 to 159	Unclear
Lotiglipron 40 mg tablet once daily LOTI_PO_40MG_QD	52.52 (4.08 to 960)	3.22 to 1195	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.

Every treatment in a row compared with every treatment in a column
Row versus column	PLACEBO	HRS7535_PO_90MG_QD	ORFO_PO_12MG_QD	SEMA_SC_16MG_QW	SEMA_SC_2p0MG_QW	SEMA_SC_8MG_QW	EXEN_SC_10UG_BID	SEMA_PO_3MG_QD	SEMA_PO_7MG_QD	EFPE_SC_6MG_QW	EFPE_SC_2MG_QW	LOTI_PO_260MG_QD	LOTI_PO_200MG_QD	LOTI_PO_80MG_QD	SITAGLIPTIN	STANDARD_CARE	LOTI_PO_160MG_QD	LOTI_PO_140MG_QD	DULA_SC_4p5MG_QW	DULA_SC_0p75MG_QW	LOTI_PO_20MG_QD	SEMA_PO_14MG_QD	EXEN_SC_5UG_BID	DULA_SC_1p5MG_QW	MAZD_SC_4p5MG_QW	DULA_SC_3p0MG_QW	MAZD_SC_3MG_QW	HRS7535_PO_30MG_QD	ORFO_PO_3MG_QD	EXENER_SC_2MG_QW	LIRA_SC_1p8MG_QD	ORFO_PO_36MG_QD	EFPE_SC_4MG_QW	LOTI_PO_40MG_QD
PLACEBO	PLACEBO	5.25 0.23 to 302	4.25 0.16 to 249	3.97 0.13 to 245	3.90 0.12 to 239	3.73 0.13 to 225	3.19 0.06 to 218	2.67 0.24 to 39.89	2.58 0.24 to 41.83	2.53 0.06 to 197	2.42 0.06 to 194	2.20 0.06 to 178	2.18 0.06 to 187	2.15 0.06 to 185	2.03 0.15 to 34.55	1.97 0.02 to 184	1.87 0.04 to 171	1.78 0.04 to 176	1.75 0.11 to 28.11	1.73 0.03 to 163	1.70 0.04 to 166	1.64 0.20 to 15.47	1.54 0.02 to 142	1.46 0.09 to 23.12	1.45 0.02 to 189	1.44 0.09 to 22.95	1.42 0.02 to 154	0.88 0.06 to 14.38	0.63 0.04 to 12.23	0.40 0.01 to 9.78	0.35 0.01 to 9.86	0.27 0.02 to 3.25	0.22 0.01 to 5.61	0.02 0.00 to 0.25
HRS7535_PO_90MG_QD	0.19 0.00 to 4.44	HRS7535_PO_90MG_QD	0.80 0.00 to 131	0.74 0.00 to 147	0.74 0.00 to 134	0.71 0.00 to 138	0.57 0.00 to 122	0.51 0.00 to 30.77	0.49 0.00 to 31.63	0.47 0.00 to 96.01	0.44 0.00 to 95.21	0.41 0.00 to 86.83	0.40 0.00 to 106	0.40 0.00 to 103	0.39 0.00 to 26.24	0.35 0.00 to 102	0.33 0.00 to 81.11	0.33 0.00 to 83.42	0.31 0.00 to 24.12	0.32 0.00 to 75.65	0.32 0.00 to 88.18	0.31 0.00 to 14.67	0.27 0.00 to 87.85	0.27 0.00 to 18.44	0.25 0.00 to 91.11	0.26 0.00 to 18.20	0.25 0.00 to 80.72	0.17 0.00 to 7.45	0.12 0.00 to 8.51	0.07 0.00 to 6.22	0.06 0.00 to 7.00	0.05 0.00 to 2.85	0.04 0.00 to 3.92	0.00 0.00 to 0.21
ORFO_PO_12MG_QD	0.24 0.00 to 6.13	1.25 0.01 to 214	ORFO_PO_12MG_QD	0.90 0.00 to 179	0.95 0.01 to 158	0.89 0.00 to 200	0.74 0.00 to 172	0.64 0.01 to 42.37	0.60 0.01 to 43.42	0.56 0.00 to 148	0.56 0.00 to 148	0.51 0.00 to 141	0.49 0.00 to 140	0.52 0.00 to 120	0.47 0.00 to 40.50	0.46 0.00 to 115	0.42 0.00 to 106	0.40 0.00 to 104	0.41 0.00 to 29.82	0.39 0.00 to 109	0.41 0.00 to 112	0.37 0.00 to 22.08	0.35 0.00 to 112	0.34 0.00 to 25.62	0.34 0.00 to 117	0.34 0.00 to 24.23	0.30 0.00 to 119	0.21 0.00 to 15.79	0.16 0.00 to 7.49	0.09 0.00 to 9.06	0.08 0.00 to 7.76	0.06 0.00 to 2.04	0.05 0.00 to 5.37	0.00 0.00 to 0.31
SEMA_SC_16MG_QW	0.25 0.00 to 7.83	1.35 0.01 to 255	1.10 0.01 to 207	SEMA_SC_16MG_QW	1.02 0.01 to 185	0.94 0.01 to 146	0.81 0.00 to 172	0.67 0.01 to 52.49	0.67 0.01 to 50.38	0.61 0.00 to 148	0.65 0.00 to 147	0.55 0.00 to 138	0.54 0.00 to 142	0.57 0.00 to 139	0.50 0.00 to 47.31	0.48 0.00 to 149	0.45 0.00 to 124	0.43 0.00 to 139	0.43 0.00 to 36.73	0.43 0.00 to 132	0.43 0.00 to 135	0.41 0.00 to 23.04	0.38 0.00 to 115	0.35 0.00 to 27.80	0.34 0.00 to 168	0.36 0.00 to 29.12	0.36 0.00 to 122	0.22 0.00 to 18.34	0.16 0.00 to 15.07	0.10 0.00 to 12.52	0.09 0.00 to 9.97	0.06 0.00 to 4.55	0.05 0.00 to 5.98	0.00 0.00 to 0.34
SEMA_SC_2p0MG_QW	0.26 0.00 to 8.04	1.36 0.01 to 274	1.05 0.01 to 197	0.98 0.01 to 191	SEMA_SC_2p0MG_QW	0.94 0.01 to 174	0.81 0.00 to 195	0.68 0.01 to 52.94	0.66 0.01 to 55.69	0.64 0.00 to 154	0.63 0.00 to 160	0.55 0.00 to 149	0.52 0.00 to 153	0.58 0.00 to 168	0.53 0.00 to 44.85	0.49 0.00 to 162	0.44 0.00 to 154	0.46 0.00 to 141	0.42 0.00 to 36.89	0.42 0.00 to 122	0.45 0.00 to 137	0.41 0.00 to 24.58	0.37 0.00 to 129	0.35 0.00 to 29.34	0.35 0.00 to 128	0.35 0.00 to 27.35	0.36 0.00 to 129	0.22 0.00 to 16.19	0.15 0.00 to 14.29	0.10 0.00 to 12.36	0.09 0.00 to 10.03	0.06 0.00 to 4.59	0.05 0.00 to 7.40	0.00 0.00 to 0.37
SEMA_SC_8MG_QW	0.27 0.00 to 7.76	1.41 0.01 to 260	1.12 0.00 to 237	1.06 0.01 to 171	1.06 0.01 to 165	SEMA_SC_8MG_QW	0.80 0.00 to 177	0.71 0.01 to 61.12	0.70 0.01 to 54.23	0.65 0.00 to 159	0.61 0.00 to 164	0.59 0.00 to 153	0.55 0.00 to 145	0.60 0.00 to 146	0.54 0.00 to 48.51	0.49 0.00 to 168	0.49 0.00 to 115	0.46 0.00 to 143	0.44 0.00 to 37.90	0.42 0.00 to 131	0.45 0.00 to 127	0.42 0.00 to 27.31	0.38 0.00 to 141	0.38 0.00 to 32.47	0.36 0.00 to 141	0.37 0.00 to 29.72	0.36 0.00 to 113	0.22 0.00 to 20.94	0.16 0.00 to 13.70	0.10 0.00 to 10.55	0.09 0.00 to 11.19	0.07 0.00 to 4.50	0.05 0.00 to 6.44	0.00 0.00 to 0.42
EXEN_SC_10UG_BID	0.31 0.00 to 16.10	1.75 0.01 to 432	1.35 0.01 to 372	1.24 0.01 to 354	1.24 0.01 to 346	1.24 0.01 to 298	EXEN_SC_10UG_BID	0.82 0.01 to 108	0.80 0.01 to 104	0.80 0.00 to 269	0.77 0.00 to 252	0.71 0.00 to 249	0.68 0.00 to 253	0.73 0.00 to 246	0.64 0.00 to 78.47	0.66 0.00 to 233	0.58 0.00 to 212	0.55 0.00 to 220	0.54 0.00 to 68.74	0.53 0.00 to 220	0.52 0.00 to 202	0.50 0.00 to 51.67	0.50 0.00 to 192	0.44 0.00 to 55.86	0.45 0.00 to 257	0.45 0.00 to 62.68	0.44 0.00 to 213	0.29 0.00 to 28.98	0.20 0.00 to 26.23	0.13 0.00 to 20.14	0.11 0.00 to 19.87	0.08 0.00 to 8.70	0.07 0.00 to 11.90	0.01 0.00 to 0.63
SEMA_PO_3MG_QD	0.38 0.03 to 4.21	1.97 0.03 to 213	1.56 0.02 to 178	1.50 0.02 to 183	1.47 0.02 to 182	1.42 0.02 to 161	1.22 0.01 to 148	SEMA_PO_3MG_QD	0.98 0.05 to 17.32	0.95 0.01 to 133	0.91 0.01 to 122	0.83 0.01 to 112	0.81 0.01 to 138	0.83 0.01 to 127	0.78 0.04 to 15.36	0.74 0.00 to 132	0.66 0.01 to 107	0.63 0.01 to 116	0.64 0.01 to 27.22	0.63 0.01 to 97.93	0.64 0.01 to 116	0.62 0.04 to 6.95	0.59 0.00 to 91.52	0.53 0.01 to 21.57	0.56 0.00 to 122	0.53 0.01 to 22.98	0.55 0.00 to 117	0.33 0.01 to 14.06	0.23 0.00 to 11.01	0.14 0.00 to 8.47	0.13 0.00 to 6.08	0.10 0.00 to 2.96	0.08 0.00 to 4.53	0.01 0.00 to 0.23
SEMA_PO_7MG_QD	0.39 0.02 to 4.14	2.03 0.03 to 240	1.65 0.02 to 164	1.49 0.02 to 183	1.52 0.02 to 172	1.42 0.02 to 152	1.25 0.01 to 149	1.02 0.06 to 19.15	SEMA_PO_7MG_QD	0.97 0.01 to 152	0.91 0.01 to 140	0.88 0.01 to 107	0.85 0.01 to 114	0.84 0.01 to 129	0.79 0.04 to 14.52	0.74 0.00 to 127	0.69 0.01 to 93.51	0.67 0.01 to 110	0.68 0.01 to 24.66	0.64 0.01 to 96.54	0.65 0.01 to 122	0.65 0.04 to 7.04	0.57 0.00 to 100	0.55 0.01 to 20.74	0.56 0.00 to 125	0.56 0.01 to 20.35	0.55 0.00 to 107	0.34 0.01 to 12.67	0.24 0.00 to 11.09	0.15 0.00 to 9.07	0.14 0.00 to 6.90	0.10 0.00 to 3.09	0.08 0.00 to 4.46	0.01 0.00 to 0.23
EFPE_SC_6MG_QW	0.39 0.01 to 18.10	2.12 0.01 to 514	1.77 0.01 to 426	1.64 0.01 to 362	1.57 0.01 to 445	1.54 0.01 to 375	1.26 0.00 to 347	1.05 0.01 to 108	1.03 0.01 to 116	EFPE_SC_6MG_QW	0.97 0.00 to 278	0.87 0.00 to 260	0.86 0.00 to 252	0.89 0.00 to 285	0.81 0.01 to 86.81	0.74 0.00 to 320	0.71 0.00 to 285	0.70 0.00 to 235	0.65 0.00 to 78.20	0.66 0.00 to 276	0.68 0.00 to 222	0.65 0.01 to 55.27	0.60 0.00 to 223	0.54 0.00 to 62.12	0.57 0.00 to 247	0.53 0.00 to 63.57	0.58 0.00 to 216	0.34 0.00 to 35.56	0.24 0.00 to 29.70	0.15 0.00 to 23.14	0.14 0.00 to 20.51	0.10 0.00 to 8.62	0.09 0.00 to 6.74	0.01 0.00 to 0.68
EFPE_SC_2MG_QW	0.41 0.01 to 17.05	2.28 0.01 to 530	1.77 0.01 to 441	1.55 0.01 to 408	1.60 0.01 to 482	1.64 0.01 to 417	1.30 0.00 to 371	1.10 0.01 to 105	1.10 0.01 to 107	1.03 0.00 to 236	EFPE_SC_2MG_QW	0.92 0.00 to 299	0.84 0.00 to 287	0.91 0.00 to 290	0.84 0.01 to 89.42	0.80 0.00 to 307	0.71 0.00 to 270	0.73 0.00 to 236	0.71 0.00 to 75.18	0.71 0.00 to 270	0.76 0.00 to 220	0.71 0.01 to 49.96	0.61 0.00 to 214	0.58 0.00 to 56.61	0.58 0.00 to 315	0.58 0.00 to 65.21	0.54 0.00 to 223	0.36 0.00 to 41.11	0.26 0.00 to 28.04	0.16 0.00 to 22.54	0.14 0.00 to 22.07	0.11 0.00 to 10.19	0.09 0.00 to 6.50	0.01 0.00 to 0.73
LOTI_PO_260MG_QD	0.46 0.01 to 15.95	2.42 0.01 to 544	1.96 0.01 to 473	1.83 0.01 to 420	1.83 0.01 to 401	1.69 0.01 to 427	1.40 0.00 to 363	1.20 0.01 to 103	1.14 0.01 to 116	1.15 0.00 to 325	1.09 0.00 to 310	LOTI_PO_260MG_QD	0.99 0.00 to 295	0.99 0.00 to 320	0.92 0.01 to 91.92	0.87 0.00 to 292	0.78 0.00 to 243	0.80 0.00 to 242	0.75 0.00 to 82.05	0.72 0.00 to 306	0.80 0.00 to 208	0.71 0.01 to 53.51	0.67 0.00 to 228	0.63 0.00 to 63.67	0.62 0.00 to 286	0.63 0.00 to 65.02	0.65 0.00 to 239	0.40 0.00 to 41.62	0.28 0.00 to 31.36	0.17 0.00 to 24.00	0.16 0.00 to 21.39	0.12 0.00 to 9.28	0.10 0.00 to 11.99	0.01 0.00 to 0.40
LOTI_PO_200MG_QD	0.46 0.01 to 17.92	2.51 0.01 to 540	2.02 0.01 to 485	1.84 0.01 to 438	1.92 0.01 to 455	1.83 0.01 to 414	1.48 0.00 to 372	1.24 0.01 to 123	1.18 0.01 to 109	1.16 0.00 to 337	1.19 0.00 to 320	1.01 0.00 to 276	LOTI_PO_200MG_QD	1.01 0.00 to 273	0.89 0.01 to 95.44	0.88 0.00 to 359	0.80 0.00 to 239	0.78 0.00 to 295	0.77 0.00 to 79.82	0.75 0.00 to 307	0.82 0.00 to 270	0.73 0.01 to 52.85	0.68 0.00 to 232	0.65 0.00 to 68.87	0.67 0.00 to 298	0.65 0.00 to 64.92	0.66 0.00 to 265	0.41 0.00 to 47.65	0.29 0.00 to 31.55	0.17 0.00 to 27.00	0.16 0.00 to 24.32	0.12 0.00 to 10.88	0.10 0.00 to 13.69	0.01 0.00 to 0.40
LOTI_PO_80MG_QD	0.46 0.01 to 17.65	2.53 0.01 to 493	1.93 0.01 to 434	1.76 0.01 to 444	1.73 0.01 to 457	1.66 0.01 to 477	1.37 0.00 to 366	1.21 0.01 to 118	1.18 0.01 to 124	1.12 0.00 to 334	1.09 0.00 to 360	1.01 0.00 to 301	0.99 0.00 to 249	LOTI_PO_80MG_QD	0.91 0.01 to 109	0.87 0.00 to 320	0.79 0.00 to 229	0.78 0.00 to 255	0.76 0.00 to 88.89	0.76 0.00 to 269	0.79 0.00 to 252	0.73 0.01 to 54.76	0.68 0.00 to 265	0.62 0.00 to 73.06	0.66 0.00 to 294	0.61 0.00 to 71.82	0.61 0.00 to 278	0.39 0.00 to 45.31	0.28 0.00 to 31.84	0.17 0.00 to 28.20	0.16 0.00 to 21.01	0.11 0.00 to 11.14	0.09 0.00 to 12.93	0.01 0.00 to 0.38
SITAGLIPTIN	0.49 0.03 to 6.48	2.59 0.04 to 300	2.13 0.02 to 236	1.98 0.02 to 259	1.90 0.02 to 238	1.86 0.02 to 242	1.57 0.01 to 225	1.29 0.07 to 26.58	1.27 0.07 to 24.98	1.24 0.01 to 194	1.19 0.01 to 178	1.09 0.01 to 160	1.12 0.01 to 155	1.10 0.01 to 170	SITAGLIPTIN	0.94 0.01 to 188	0.90 0.01 to 138	0.85 0.01 to 168	0.85 0.02 to 36.22	0.85 0.01 to 123	0.88 0.01 to 158	0.81 0.05 to 10.88	0.75 0.00 to 133	0.69 0.01 to 30.33	0.70 0.00 to 169	0.69 0.01 to 33.17	0.70 0.00 to 144	0.43 0.01 to 18.86	0.31 0.01 to 15.36	0.18 0.00 to 12.15	0.18 0.00 to 9.71	0.13 0.00 to 4.46	0.11 0.00 to 6.62	0.01 0.00 to 0.35
STANDARD_CARE	0.51 0.01 to 40.24	2.89 0.01 to 881	2.18 0.01 to 823	2.09 0.01 to 722	2.05 0.01 to 849	2.06 0.01 to 681	1.51 0.00 to 667	1.34 0.01 to 252	1.36 0.01 to 225	1.36 0.00 to 594	1.25 0.00 to 477	1.14 0.00 to 640	1.14 0.00 to 500	1.15 0.00 to 558	1.07 0.01 to 197	STANDARD_CARE	0.92 0.00 to 462	0.94 0.00 to 432	0.87 0.00 to 160	0.90 0.00 to 439	0.91 0.00 to 506	0.79 0.01 to 122	0.79 0.00 to 424	0.72 0.00 to 119	0.75 0.00 to 510	0.72 0.00 to 135	0.68 0.00 to 413	0.44 0.00 to 83.54	0.31 0.00 to 53.88	0.21 0.00 to 45.11	0.17 0.00 to 42.07	0.12 0.00 to 20.91	0.11 0.00 to 29.07	0.01 0.00 to 1.65
LOTI_PO_160MG_QD	0.54 0.01 to 25.70	3.01 0.01 to 708	2.41 0.01 to 639	2.22 0.01 to 614	2.25 0.01 to 653	2.04 0.01 to 649	1.73 0.00 to 584	1.52 0.01 to 157	1.45 0.01 to 152	1.42 0.00 to 508	1.41 0.00 to 502	1.27 0.00 to 376	1.26 0.00 to 352	1.27 0.00 to 385	1.11 0.01 to 126	1.09 0.00 to 401	LOTI_PO_160MG_QD	1.02 0.00 to 383	0.93 0.01 to 112	0.94 0.00 to 362	0.99 0.00 to 313	0.93 0.01 to 72.68	0.83 0.00 to 371	0.76 0.00 to 96.41	0.78 0.00 to 438	0.77 0.00 to 93.57	0.79 0.00 to 346	0.50 0.00 to 59.70	0.35 0.00 to 46.18	0.22 0.00 to 35.04	0.19 0.00 to 28.22	0.14 0.00 to 15.75	0.12 0.00 to 21.14	0.01 0.00 to 0.56
LOTI_PO_140MG_QD	0.56 0.01 to 27.68	3.05 0.01 to 846	2.50 0.01 to 704	2.32 0.01 to 624	2.17 0.01 to 667	2.17 0.01 to 539	1.80 0.00 to 555	1.58 0.01 to 164	1.49 0.01 to 152	1.42 0.00 to 510	1.37 0.00 to 483	1.25 0.00 to 375	1.28 0.00 to 394	1.29 0.00 to 394	1.18 0.01 to 147	1.07 0.00 to 440	0.98 0.00 to 366	LOTI_PO_140MG_QD	0.97 0.00 to 124	0.92 0.00 to 402	0.97 0.00 to 393	0.90 0.01 to 78.87	0.90 0.00 to 337	0.78 0.00 to 89.44	0.79 0.00 to 344	0.78 0.00 to 96.12	0.82 0.00 to 330	0.49 0.00 to 54.92	0.36 0.00 to 49.15	0.22 0.00 to 36.40	0.20 0.00 to 32.20	0.14 0.00 to 15.89	0.12 0.00 to 20.01	0.01 0.00 to 0.60
DULA_SC_4p5MG_QW	0.57 0.04 to 9.49	3.22 0.04 to 385	2.44 0.03 to 348	2.33 0.03 to 316	2.38 0.03 to 331	2.29 0.03 to 310	1.86 0.01 to 310	1.57 0.04 to 67.93	1.47 0.04 to 74.19	1.55 0.01 to 247	1.40 0.01 to 241	1.33 0.01 to 214	1.30 0.01 to 218	1.32 0.01 to 227	1.18 0.03 to 60.82	1.15 0.01 to 231	1.08 0.01 to 181	1.03 0.01 to 217	DULA_SC_4p5MG_QW	1.00 0.01 to 191	1.00 0.01 to 203	0.95 0.03 to 31.46	0.89 0.00 to 179	0.82 0.18 to 3.84	0.88 0.00 to 221	0.82 0.17 to 3.93	0.81 0.01 to 189	0.51 0.01 to 26.71	0.36 0.01 to 21.93	0.23 0.00 to 15.52	0.20 0.00 to 14.52	0.15 0.00 to 6.26	0.12 0.00 to 8.65	0.01 0.00 to 0.47
DULA_SC_0p75MG_QW	0.58 0.01 to 38.31	3.12 0.01 to 1042	2.53 0.01 to 836	2.34 0.01 to 836	2.40 0.01 to 859	2.37 0.01 to 755	1.87 0.00 to 681	1.60 0.01 to 194	1.57 0.01 to 177	1.51 0.00 to 586	1.40 0.00 to 567	1.39 0.00 to 597	1.34 0.00 to 610	1.32 0.00 to 560	1.18 0.01 to 160	1.11 0.00 to 641	1.06 0.00 to 412	1.09 0.00 to 474	1.00 0.01 to 143	DULA_SC_0p75MG_QW	1.05 0.00 to 508	0.97 0.01 to 90.21	0.89 0.00 to 455	0.81 0.00 to 116	0.85 0.00 to 470	0.83 0.00 to 111	0.87 0.00 to 424	0.51 0.00 to 82.05	0.37 0.00 to 55.97	0.23 0.00 to 47.36	0.20 0.00 to 48.11	0.15 0.00 to 19.82	0.13 0.00 to 25.26	0.01 0.00 to 1.64
LOTI_PO_20MG_QD	0.59 0.01 to 23.73	3.08 0.01 to 801	2.46 0.01 to 731	2.33 0.01 to 548	2.23 0.01 to 668	2.23 0.01 to 572	1.93 0.00 to 579	1.56 0.01 to 150	1.53 0.01 to 150	1.48 0.00 to 456	1.32 0.00 to 458	1.25 0.00 to 364	1.22 0.00 to 400	1.26 0.00 to 446	1.14 0.01 to 138	1.10 0.00 to 434	1.02 0.00 to 356	1.03 0.00 to 372	1.00 0.00 to 111	0.95 0.00 to 384	LOTI_PO_20MG_QD	0.94 0.01 to 72.94	0.85 0.00 to 326	0.82 0.00 to 90.39	0.86 0.00 to 396	0.82 0.00 to 92.86	0.80 0.00 to 313	0.51 0.00 to 50.99	0.36 0.00 to 40.91	0.21 0.00 to 36.72	0.19 0.00 to 27.81	0.14 0.00 to 15.73	0.12 0.00 to 17.78	0.01 0.00 to 0.58
SEMA_PO_14MG_QD	0.61 0.06 to 4.89	3.19 0.07 to 307	2.69 0.05 to 231	2.46 0.04 to 257	2.42 0.04 to 271	2.37 0.04 to 220	2.02 0.02 to 207	1.61 0.14 to 24.48	1.55 0.14 to 23.28	1.54 0.02 to 188	1.41 0.02 to 184	1.41 0.02 to 149	1.37 0.02 to 153	1.36 0.02 to 179	1.24 0.09 to 19.04	1.26 0.01 to 166	1.07 0.01 to 146	1.11 0.01 to 151	1.05 0.03 to 34.17	1.03 0.01 to 130	1.07 0.01 to 171	SEMA_PO_14MG_QD	0.94 0.01 to 142	0.88 0.02 to 27.85	0.91 0.01 to 169	0.87 0.03 to 28.52	0.89 0.01 to 143	0.55 0.02 to 16.72	0.39 0.01 to 14.76	0.24 0.00 to 12.11	0.23 0.01 to 6.89	0.16 0.01 to 4.26	0.13 0.00 to 6.64	0.01 0.00 to 0.27
EXEN_SC_5UG_BID	0.65 0.01 to 53.05	3.75 0.01 to 1443	2.83 0.01 to 1035	2.60 0.01 to 1029	2.71 0.01 to 1088	2.66 0.01 to 1075	2.02 0.01 to 1135	1.69 0.01 to 303	1.75 0.01 to 323	1.67 0.00 to 756	1.65 0.00 to 794	1.49 0.00 to 770	1.47 0.00 to 604	1.48 0.00 to 789	1.33 0.01 to 251	1.26 0.00 to 805	1.20 0.00 to 576	1.11 0.00 to 666	1.13 0.01 to 235	1.13 0.00 to 691	1.18 0.00 to 617	1.06 0.01 to 154	EXEN_SC_5UG_BID	0.93 0.00 to 194	0.97 0.00 to 689	0.92 0.00 to 180	0.93 0.00 to 572	0.60 0.00 to 109	0.42 0.00 to 78.89	0.23 0.00 to 59.36	0.23 0.00 to 54.08	0.16 0.00 to 29.42	0.14 0.00 to 34.68	0.01 0.00 to 2.03
DULA_SC_1p5MG_QW	0.69 0.04 to 10.80	3.77 0.05 to 480	2.98 0.04 to 427	2.84 0.04 to 427	2.82 0.03 to 379	2.64 0.03 to 360	2.26 0.02 to 338	1.90 0.05 to 82.89	1.82 0.05 to 83.15	1.84 0.02 to 262	1.71 0.02 to 283	1.58 0.02 to 233	1.54 0.01 to 265	1.63 0.01 to 309	1.45 0.03 to 67.90	1.40 0.01 to 292	1.31 0.01 to 238	1.27 0.01 to 244	1.22 0.26 to 5.65	1.23 0.01 to 228	1.21 0.01 to 245	1.13 0.04 to 40.40	1.08 0.01 to 205	DULA_SC_1p5MG_QW	1.08 0.01 to 233	1.00 0.22 to 4.45	1.04 0.01 to 221	0.61 0.01 to 31.63	0.44 0.01 to 22.73	0.27 0.00 to 18.54	0.25 0.00 to 17.15	0.18 0.00 to 7.34	0.15 0.00 to 10.70	0.01 0.00 to 0.58
MAZD_SC_4p5MG_QW	0.69 0.01 to 52.19	3.94 0.01 to 1197	2.98 0.01 to 1126	2.93 0.01 to 1022	2.83 0.01 to 989	2.80 0.01 to 1095	2.24 0.00 to 1035	1.80 0.01 to 319	1.78 0.01 to 314	1.75 0.00 to 735	1.73 0.00 to 758	1.60 0.00 to 701	1.50 0.00 to 706	1.51 0.00 to 664	1.42 0.01 to 270	1.33 0.00 to 711	1.28 0.00 to 600	1.27 0.00 to 612	1.14 0.00 to 216	1.17 0.00 to 603	1.16 0.00 to 700	1.09 0.01 to 150	1.03 0.00 to 547	0.93 0.00 to 174	MAZD_SC_4p5MG_QW	0.94 0.00 to 166	0.99 0.00 to 509	0.59 0.00 to 105	0.42 0.00 to 90.92	0.24 0.00 to 63.52	0.23 0.00 to 54.03	0.17 0.00 to 26.01	0.14 0.00 to 36.32	0.01 0.00 to 1.93
DULA_SC_3p0MG_QW	0.70 0.04 to 10.93	3.84 0.05 to 468	2.96 0.04 to 407	2.78 0.03 to 386	2.87 0.04 to 367	2.70 0.03 to 390	2.24 0.02 to 409	1.90 0.04 to 85.55	1.78 0.05 to 88.66	1.87 0.02 to 286	1.73 0.02 to 278	1.59 0.02 to 265	1.54 0.02 to 259	1.63 0.01 to 297	1.44 0.03 to 71.62	1.38 0.01 to 275	1.30 0.01 to 236	1.28 0.01 to 223	1.22 0.25 to 5.72	1.21 0.01 to 212	1.23 0.01 to 256	1.15 0.04 to 39.43	1.09 0.01 to 222	1.00 0.22 to 4.58	1.06 0.01 to 233	DULA_SC_3p0MG_QW	0.99 0.01 to 223	0.63 0.01 to 31.91	0.45 0.01 to 24.52	0.28 0.00 to 18.46	0.25 0.00 to 15.76	0.18 0.00 to 7.57	0.15 0.00 to 10.63	0.01 0.00 to 0.61
MAZD_SC_3MG_QW	0.70 0.01 to 52.88	3.94 0.01 to 1213	3.29 0.01 to 1067	2.77 0.01 to 974	2.77 0.01 to 1150	2.76 0.01 to 979	2.25 0.00 to 1100	1.81 0.01 to 318	1.82 0.01 to 296	1.73 0.00 to 770	1.84 0.00 to 788	1.53 0.00 to 758	1.52 0.00 to 660	1.64 0.00 to 770	1.43 0.01 to 261	1.48 0.00 to 802	1.27 0.00 to 567	1.22 0.00 to 714	1.23 0.01 to 187	1.15 0.00 to 646	1.25 0.00 to 655	1.12 0.01 to 153	1.07 0.00 to 502	0.96 0.00 to 161	1.01 0.00 to 540	1.01 0.00 to 139	MAZD_SC_3MG_QW	0.61 0.00 to 98.13	0.44 0.00 to 80.42	0.26 0.00 to 62.93	0.25 0.00 to 64.21	0.19 0.00 to 25.70	0.15 0.00 to 36.38	0.01 0.00 to 2.04
HRS7535_PO_30MG_QD	1.13 0.07 to 16.41	5.93 0.13 to 568	4.68 0.06 to 612	4.50 0.05 to 518	4.56 0.06 to 602	4.52 0.05 to 544	3.48 0.03 to 533	3.05 0.07 to 131	2.91 0.08 to 135	2.90 0.03 to 460	2.79 0.02 to 474	2.47 0.02 to 440	2.45 0.02 to 477	2.56 0.02 to 488	2.31 0.05 to 113	2.25 0.01 to 471	1.99 0.02 to 359	2.05 0.02 to 377	1.98 0.04 to 89.65	1.97 0.01 to 356	1.96 0.02 to 391	1.81 0.06 to 62.09	1.68 0.01 to 328	1.64 0.03 to 76.75	1.70 0.01 to 450	1.60 0.03 to 74.14	1.65 0.01 to 381	HRS7535_PO_30MG_QD	0.73 0.02 to 36.45	0.46 0.01 to 26.35	0.39 0.01 to 29.89	0.29 0.01 to 10.51	0.24 0.00 to 17.50	0.02 0.00 to 0.88
ORFO_PO_3MG_QD	1.59 0.08 to 24.33	8.68 0.12 to 885	6.34 0.13 to 668	6.37 0.07 to 819	6.48 0.07 to 811	6.15 0.07 to 785	5.08 0.04 to 721	4.30 0.09 to 207	4.11 0.09 to 205	4.18 0.03 to 590	3.87 0.04 to 686	3.57 0.03 to 550	3.42 0.03 to 583	3.56 0.03 to 519	3.20 0.07 to 171	3.21 0.02 to 607	2.82 0.02 to 575	2.81 0.02 to 546	2.76 0.05 to 135	2.72 0.02 to 539	2.81 0.02 to 520	2.55 0.07 to 90.93	2.39 0.01 to 459	2.27 0.04 to 108	2.35 0.01 to 513	2.24 0.04 to 109	2.27 0.01 to 558	1.36 0.03 to 66.44	ORFO_PO_3MG_QD	0.63 0.01 to 41.17	0.56 0.01 to 39.93	0.42 0.02 to 6.16	0.33 0.00 to 24.13	0.03 0.00 to 1.31
EXENER_SC_2MG_QW	2.51 0.10 to 76.21	14.40 0.16 to 2508	10.93 0.11 to 2100	10.24 0.08 to 2113	10.04 0.08 to 2302	9.86 0.09 to 1906	7.71 0.05 to 1923	6.95 0.12 to 487	6.69 0.11 to 497	6.57 0.04 to 1668	6.23 0.04 to 1665	5.72 0.04 to 1269	5.98 0.04 to 1409	5.90 0.04 to 1426	5.41 0.08 to 363	4.87 0.02 to 1573	4.61 0.03 to 1284	4.62 0.03 to 1332	4.26 0.06 to 363	4.28 0.02 to 1485	4.65 0.03 to 1231	4.10 0.08 to 228	4.27 0.02 to 943	3.64 0.05 to 293	4.13 0.02 to 1159	3.56 0.05 to 306	3.80 0.02 to 1079	2.16 0.04 to 189	1.57 0.02 to 125	EXENER_SC_2MG_QW	0.90 0.01 to 105	0.66 0.01 to 43.59	0.56 0.01 to 60.42	0.05 0.00 to 3.45
LIRA_SC_1p8MG_QD	2.83 0.10 to 72.03	15.57 0.14 to 2731	12.46 0.13 to 2056	11.35 0.10 to 1896	11.76 0.10 to 1976	11.18 0.09 to 2198	9.13 0.05 to 2202	7.57 0.16 to 411	7.37 0.14 to 487	7.31 0.05 to 1612	6.96 0.05 to 1886	6.21 0.05 to 1349	6.24 0.04 to 1515	6.41 0.05 to 1468	5.71 0.10 to 382	5.89 0.02 to 1431	5.14 0.04 to 1165	5.13 0.03 to 1224	4.94 0.07 to 368	5.11 0.02 to 1297	5.26 0.04 to 1267	4.44 0.15 to 180	4.38 0.02 to 1216	4.06 0.06 to 285	4.33 0.02 to 1404	4.08 0.06 to 287	3.95 0.02 to 1405	2.59 0.03 to 178	1.78 0.03 to 149	1.11 0.01 to 112	LIRA_SC_1p8MG_QD	0.74 0.01 to 42.06	0.62 0.01 to 62.55	0.05 0.00 to 3.02
ORFO_PO_36MG_QD	3.77 0.31 to 50.02	21.57 0.35 to 2334	15.42 0.49 to 1516	15.48 0.22 to 1769	15.96 0.22 to 1954	14.99 0.22 to 1970	13.03 0.11 to 1764	10.36 0.34 to 460	9.99 0.32 to 424	10.23 0.12 to 1274	9.36 0.10 to 1512	8.36 0.11 to 1423	8.54 0.09 to 1348	8.78 0.09 to 1328	7.84 0.22 to 390	8.03 0.05 to 1429	6.96 0.06 to 1143	7.17 0.06 to 1273	6.72 0.16 to 293	6.60 0.05 to 1352	6.98 0.06 to 1229	6.27 0.23 to 194	6.09 0.03 to 1155	5.53 0.14 to 236	5.96 0.04 to 1170	5.60 0.13 to 244	5.40 0.04 to 1239	3.46 0.10 to 149	2.37 0.16 to 53.60	1.51 0.02 to 90.65	1.36 0.02 to 90.11	ORFO_PO_36MG_QD	0.86 0.01 to 48.76	0.07 0.00 to 2.71
EFPE_SC_4MG_QW	4.60 0.18 to 136	26.00 0.25 to 4381	20.32 0.19 to 3771	18.84 0.17 to 3790	19.11 0.14 to 3624	19.00 0.16 to 3488	15.08 0.08 to 3059	12.47 0.22 to 849	12.76 0.22 to 800	11.11 0.15 to 2179	10.81 0.15 to 2080	10.31 0.08 to 2601	10.45 0.07 to 2517	10.78 0.08 to 2569	9.44 0.15 to 824	9.32 0.03 to 2548	8.55 0.05 to 2094	8.23 0.05 to 2322	8.30 0.12 to 639	7.70 0.04 to 2362	8.47 0.06 to 2148	7.60 0.15 to 427	7.18 0.03 to 2011	6.88 0.09 to 504	7.05 0.03 to 2482	6.52 0.09 to 509	6.68 0.03 to 2259	4.18 0.06 to 388	3.01 0.04 to 234	1.78 0.02 to 180	1.62 0.02 to 173	1.17 0.02 to 75.34	EFPE_SC_4MG_QW	0.09 0.00 to 5.52
LOTI_PO_40MG_QD	52.52 4.08 to 960	290 4.85 to 38755	232 3.26 to 31233	221 2.95 to 26772	220 2.70 to 30169	210 2.40 to 32579	175 1.59 to 28012	144 4.36 to 6929	137 4.26 to 7257	141 1.48 to 22681	134 1.36 to 25271	109 2.52 to 18753	111 2.51 to 17820	109 2.62 to 19255	110 2.82 to 5669	110 0.61 to 23543	91.86 1.77 to 17700	89.08 1.68 to 19271	92.72 2.13 to 5110	93.83 0.61 to 18902	90.33 1.71 to 16002	86.80 3.67 to 2989	83.92 0.49 to 18317	76.72 1.73 to 4278	84.36 0.52 to 20299	76.22 1.65 to 4054	80.09 0.49 to 17682	48.07 1.14 to 2641	34.67 0.76 to 1969	21.59 0.29 to 1650	19.85 0.33 to 1299	14.04 0.37 to 578	11.26 0.18 to 849	LOTI_PO_40MG_QD

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau): 0.330 (95% CrI 0.074 to 1.206), log scale
Residual deviance: 36.4 for 58 data points
DIC: 55.1 (pD 18.7)
Largest R-hat: 1.002
Smallest ESS: bulk 2,897, tail 4,189
Divergent transitions: 0
Convergence: All criteria met
Priors: PR02 N(0, 5^2); PR05 N(0, 2.5^2); PR09 log normal(-2.1, 1.58^2) on tau^2 (Adverse events, pharm vs pharm)

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.

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.

NoteOutcome assessment, time point: selected time points span 0.43 to 62 weeks
NoteOutcome assessment, analysis set: mixed: full_analysis 1, randomized 1, safety 14
NoteOutcome assessment, definition: mixed: documented, confirmed plasma glucose below 54 mg/dL 1, EAC confirmed acute kidney injury 1, hypoglycemia requiring medical assistance 1, level 3 severe hypoglycemia 1, minor: symptomatic, glucose below 3.0 mmol/L, not major 1, not stated 11
NoteOutcome assessment, adjudicated: mixed: not stated 12, yes 4
NoteOutcome assessment, intercurrent events (discontinuation): mixed: not stated 15, while_on_treatment 1
NoteOutcome assessment, intercurrent events (rescue): mixed: not stated 15, treatment_policy 1
NoteRisk of bias, blinding: mixed: double_blind 13, open_label 2, single_blind 1
NoteRisk of bias, funding: mixed: industry 14, non_industry 2
NoteData handling, input conversions: arms_combined 4, nonserious_only 21, printed_denominator 2

Comparability items per trial
Trial	blinding	time weeks	analysis set	definition	instrument	adjudicated	proportion method	intercurrent events (discontinuation)	intercurrent events (rescue)	funding	start year	Eligibility
AWARD-11	double_blind	52	safety	documented, confirmed plasma glucose below 54 mg/dL	not stated	not stated	not stated	not stated	not stated	industry	2018	age 18 or older; HbA1c 7.5 to 11.0%; BMI 25 or more; metformin 1500 mg/day or more; GLP-1 RA and insulin naive
PIONEER 4	double_blind	57	safety	not stated	not stated	yes	not stated	not stated	not stated	industry	2016	Age 18 or older; T2D on metformin with or without SGLT2i; HbA1c 7.0 to 9.5 percent; eGFR 60 or more
PIONEER 10	single_blind	57	safety	not stated	not stated	yes	not stated	while_on_treatment	treatment_policy	industry	2017	Japanese adults 20 or older; T2D; HbA1c 7.0 to 10.5 percent on one oral glucose lowering drug
NCT00765817	double_blind	30	full_analysis	not stated	not stated	not stated	not stated	not stated	not stated	industry	2008	adults 18 or older; insulin glargine 20 U/d or more alone or with metformin or pioglitazone; HbA1c 7.1 to 10.5 percent; BMI 45 or less
NCT05579977	double_blind	28	safety	not stated	not stated	not stated	not stated	not stated	not stated	industry	2022	age 18 to 75; T2D cohort on metformin, HbA1c 7.0 to 10.0, BMI 23 or more; obesity cohort BMI 30 or more without diabetes
PIONEER 12	double_blind	31	safety	EAC confirmed acute kidney injury	not stated	yes	not stated	not stated	not stated	industry	2019	adults with type 2 diabetes on metformin, HbA1c 7.0 to 10.5 percent
NCT02229383	double_blind	38	safety	minor: symptomatic, glucose below 3.0 mmol/L, not major	not stated	not stated	not stated	not stated	not stated	industry	2014	adults; insulin glargine 20 U/d or more with or without metformin; HbA1c 7.0 to 10.5 percent at randomization
ACHIEVE-5	double_blind	42	safety	not stated	not stated	not stated	not stated	not stated	not stated	industry	2023	adults with T2D on insulin glargine with or without metformin or SGLT2 inhibitor
SOLID-DKD	double_blind	18	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
NCT05486065	double_blind	49	safety	not stated	not stated	not stated	not stated	not stated	not stated	industry	2022	age 18 to 64; HbA1c 7.0 to 10.5; BMI 27 or more; on metformin
PIONEER 11	double_blind	31	safety	not stated	not stated	yes	not stated	not stated	not stated	industry	2019	age 18 or older; HbA1c 7.0 to 10.0 percent at screening, 7.0 to 9.5 at randomization; no glucose lowering drugs; eGFR 60 or more
AGAC2	open_label	0.43	randomized	not stated	not stated	not stated	not stated	not stated	not stated	non_industry	2011	age over 20, T2DM over 2 years, A1C 8 to 12 percent, premixed insulin twice daily over 0.6 U/kg/day
ACHIEVE-1	double_blind	42	safety	not stated	not stated	not stated	not stated	not stated	not stated	industry	2023	adults with type 2 diabetes on diet and exercise alone; HbA1c 7.0 to 9.5 percent
AMPLITUDE-M	double_blind	62	safety	not stated	not stated	not stated	not stated	not stated	not stated	industry	2017	type 2 diabetes on diet and exercise, HbA1c 7 to 10 percent, no glucose lowering drug in prior 3 months
NCT04466904	double_blind	20	safety	not stated	not stated	not stated	not stated	not stated	not stated	industry	2020	age 18 to 75; T2D on diet and exercise or stable metformin; HbA1c 7.5 to 11.0 percent; BMI 20 to 35
S003079	open_label	5	safety	hypoglycemia requiring medical assistance	not stated	not stated	not stated	not stated	not stated	non_industry	2010	age 18 to 80, HbA1c 7.5 to 12 percent, BMI 21 to 35, T2D at least 6 months

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 data entering this analysis
Trial	Arm	Treatment	Week	Data	Events / N	Flags	Source
AWARD-11	A1	DULA_SC_1p5MG_QW	52	arm, events	6 / 612		R0022783:Table 2
AWARD-11	A2	DULA_SC_3p0MG_QW	52	arm, events	6 / 616		R0022783:Table 2
AWARD-11	A3	DULA_SC_4p5MG_QW	52	arm, events	5 / 614		R0022783:Table 2
PIONEER 4	A1	SEMA_PO_14MG_QD	57	arm, events	0 / 285		R0015836:Supplement Table S8
PIONEER 4	A2	LIRA_SC_1p8MG_QD	57	arm, events	1 / 284		R0015836:Supplement Table S8
PIONEER 4	A3	PLACEBO	57	arm, events	0 / 142		R0015836:Supplement Table S8
PIONEER 10	A1	SEMA_PO_3MG_QD	57	arm, events	0 / 131		R0018421:Table 2
PIONEER 10	A2	SEMA_PO_7MG_QD	57	arm, events	0 / 132		R0018421:Table 2
PIONEER 10	A3	SEMA_PO_14MG_QD	57	arm, events	0 / 130		R0018421:Table 2
PIONEER 10	A4	DULA_SC_0p75MG_QW	57	arm, events	0 / 65		R0018421:Table 2
NCT00765817	A1	EXEN_SC_10UG_BID	30	arm, events	0 / 138		R0027069:Results
NCT00765817	A2	PLACEBO	30	arm, events	0 / 123		R0027069:Results
NCT05579977	A1+A8	PLACEBO	28	arm, events	0 / 139	nonserious_only;arms_combined	registry:adverse_events
NCT05579977	A10	LOTI_PO_140MG_QD	28	arm, events	0 / 64	nonserious_only	registry:adverse_events
NCT05579977	A11+A12	LOTI_PO_200MG_QD	28	arm, events	0 / 131	nonserious_only;arms_combined	registry:adverse_events
NCT05579977	A13+A6	LOTI_PO_260MG_QD	28	arm, events	0 / 138	nonserious_only;arms_combined	registry:adverse_events
NCT05579977	A2	LOTI_PO_20MG_QD	28	arm, events	0 / 73	nonserious_only	registry:adverse_events
NCT05579977	A3	LOTI_PO_40MG_QD	28	arm, events	3 / 72	nonserious_only	registry:adverse_events
NCT05579977	A4+A9	LOTI_PO_80MG_QD	28	arm, events	0 / 139	nonserious_only;arms_combined	registry:adverse_events
NCT05579977	A5	LOTI_PO_160MG_QD	28	arm, events	0 / 73	nonserious_only	registry:adverse_events
NCT05579977	A7	SEMA_PO_14MG_QD	28	arm, events	0 / 73	nonserious_only	registry:adverse_events
PIONEER 12	A1	SEMA_PO_3MG_QD	31	arm, events	1 / 361		R0019776:ESM Table 4
PIONEER 12	A2	SEMA_PO_7MG_QD	31	arm, events	0 / 360		R0019776:ESM Table 4
PIONEER 12	A3	SEMA_PO_14MG_QD	31	arm, events	2 / 361		R0019776:ESM Table 4
PIONEER 12	A4	SITAGLIPTIN	31	arm, events	1 / 359		R0019776:ESM Table 4
NCT02229383	A1	EXENER_SC_2MG_QW	38	arm, events	1 / 233		R0014763:Table 3
NCT02229383	A2	PLACEBO	38	arm, events	0 / 231		R0014763:Table 3
ACHIEVE-5	A1	PLACEBO	42	arm, events	0 / 141	nonserious_only	registry:adverse_events
ACHIEVE-5	A2	ORFO_PO_3MG_QD	42	arm, events	0 / 137	nonserious_only	registry:adverse_events
ACHIEVE-5	A3	ORFO_PO_12MG_QD	42	arm, events	0 / 132	nonserious_only	registry:adverse_events
ACHIEVE-5	A4	ORFO_PO_36MG_QD	42	arm, events	1 / 136	nonserious_only	registry:adverse_events
SOLID-DKD	A1	HRS7535_PO_30MG_QD	18	arm, events	1 / 93		R0004355:Table 2
SOLID-DKD	A2	HRS7535_PO_90MG_QD	18	arm, events	0 / 94		R0004355:Table 2
SOLID-DKD	A3	PLACEBO	18	arm, events	1 / 94		R0004355:Table 2
NCT05486065	A1	SEMA_SC_2p0MG_QW	49	arm, events	0 / 61		R0005510:Table 2
NCT05486065	A2	SEMA_SC_8MG_QW	49	arm, events	0 / 62		R0005510:Table 2
NCT05486065	A3	SEMA_SC_16MG_QW	49	arm, events	0 / 62		R0005510:Table 2
NCT05486065	A4	PLACEBO	49	arm, events	1 / 60		R0005510:Table 2
PIONEER 11	A1	SEMA_PO_3MG_QD	31	arm, events	0 / 130		R0019663:Supplement Table 6
PIONEER 11	A2	SEMA_PO_7MG_QD	31	arm, events	1 / 130		R0019663:Supplement Table 6
PIONEER 11	A3	SEMA_PO_14MG_QD	31	arm, events	0 / 130		R0019663:Supplement Table 6
PIONEER 11	A4	PLACEBO	31	arm, events	0 / 131		R0019663:Supplement Table 6
AGAC2	A1	PLACEBO	0.43	arm, events	0 / 21		R0020827:Results
AGAC2	A2	EXEN_SC_5UG_BID	0.43	arm, events	0 / 30		R0020827:Results
ACHIEVE-1	A1	PLACEBO	42	arm, events	0 / 138	nonserious_only	registry:adverse_events
ACHIEVE-1	A2	ORFO_PO_3MG_QD	42	arm, events	1 / 143	nonserious_only	registry:adverse_events
ACHIEVE-1	A3	ORFO_PO_12MG_QD	42	arm, events	0 / 137	nonserious_only	registry:adverse_events
ACHIEVE-1	A4	ORFO_PO_36MG_QD	42	arm, events	1 / 141	nonserious_only	registry:adverse_events
AMPLITUDE-M	A1	EFPE_SC_2MG_QW	62	arm, events	0 / 100	nonserious_only	registry:adverse_events
AMPLITUDE-M	A2	EFPE_SC_4MG_QW	62	arm, events	1 / 101	nonserious_only	registry:adverse_events
AMPLITUDE-M	A3	EFPE_SC_6MG_QW	62	arm, events	0 / 103	nonserious_only	registry:adverse_events
AMPLITUDE-M	A4	PLACEBO	62	arm, events	0 / 102	nonserious_only	registry:adverse_events
NCT04466904	A1	MAZD_SC_3MG_QW	20	arm, events	0 / 8		R0009340:Supplement Table S3
NCT04466904	A2	MAZD_SC_4p5MG_QW	20	arm, events	0 / 8		R0009340:Supplement Table S3
NCT04466904	A4	DULA_SC_1p5MG_QW	20	arm, events	0 / 6	printed_denominator	R0009340:Supplement Table S3
NCT04466904	A5	PLACEBO	20	arm, events	0 / 12	printed_denominator	R0009340:Supplement Table S3
S003079	A1	EXEN_SC_10UG_BID	5	arm, events	0 / 18		R0025923:Results
S003079	A2	STANDARD_CARE	5	arm, events	0 / 18		R0025923:Results

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