Network meta-analysis

Diabetic retinopathy complications

Type 2 diabetes (adults)

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

Randomized trials

Treatments

26,376

Participants

530

Events

In plain language

Across 10 trials with 26,376 participants, 0 of 20 treatments had a clearly better result than placebo on diabetic retinopathy complications, and for 20 the evidence could not tell them apart from placebo. The most favorable estimate was for Semaglutide 8 mg injection once weekly: hazard ratio (from event counts) 0.40 (95% credible interval 0.00 to 16.84).

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
Semaglutide 8 mg injection once weekly SEMA_SC_8MG_QW	0.40 (0.00 to 16.84)	0.00 to 19.25	Unclear
Semaglutide 2.0 mg subcutaneous once weekly SEMA_SC_2p0MG_QW	0.41 (0.01 to 16.45)	0.00 to 17.64	Unclear
Ecnoglutide 1.2 mg injection once weekly ECNO_SC_1p2MG_QW	0.64 (0.01 to 50.05)	0.01 to 51.00	Unclear
Ecnoglutide 0.4 mg injection once weekly ECNO_SC_0p4MG_QW	0.64 (0.01 to 44.54)	0.01 to 47.37	Unclear
Ecnoglutide 0.8 mg injection once weekly ECNO_SC_0p8MG_QW	0.65 (0.01 to 47.83)	0.01 to 51.81	Unclear
Tirzepatide 1 mg subcutaneous once weekly TIRZ_SC_1MG_QW	0.68 (0.01 to 49.66)	0.01 to 50.98	Unclear
Tirzepatide 10 mg subcutaneous once weekly TIRZ_SC_10MG_QW	0.69 (0.01 to 56.73)	0.01 to 56.78	Unclear
Tirzepatide 15 mg subcutaneous once weekly TIRZ_SC_15MG_QW	0.69 (0.01 to 46.52)	0.01 to 50.11	Unclear
Tirzepatide 5 mg subcutaneous once weekly TIRZ_SC_5MG_QW	0.70 (0.01 to 47.78)	0.01 to 50.63	Unclear
Liraglutide 1.8 mg subcutaneous once daily LIRA_SC_1p8MG_QD	0.73 (0.15 to 3.50)	0.12 to 4.02	Unclear
Albiglutide flexible dose injection once weekly ALBI_SC_FLEX_30-50_QW	0.88 (0.39 to 1.99)	0.28 to 2.77	Unclear
Dulaglutide 0.75 mg subcutaneous once weekly DULA_SC_0p75MG_QW	0.93 (0.14 to 5.14)	0.12 to 5.80	Unclear
Dulaglutide 1.5 mg subcutaneous once weekly DULA_SC_1p5MG_QW	1.24 (0.51 to 2.66)	0.37 to 3.59	Unclear
Semaglutide 14 mg oral once daily (original tablet) SEMA_PO_14MG_QD	1.35 (0.40 to 5.11)	0.32 to 6.13	Unclear
Semaglutide 1.0 mg subcutaneous once weekly SEMA_SC_1p0MG_QW	1.69 (0.72 to 3.85)	0.54 to 5.38	Unclear
Semaglutide 7 mg oral once daily (original tablet) SEMA_PO_7MG_QD	1.73 (0.42 to 7.33)	0.35 to 8.37	Unclear
Semaglutide 3 mg oral once daily (original tablet) SEMA_PO_3MG_QD	1.77 (0.44 to 7.55)	0.38 to 8.57	Unclear
Semaglutide 0.5 mg subcutaneous once weekly SEMA_SC_0p5MG_QW	2.05 (0.94 to 5.14)	0.73 to 7.08	Unclear
Sitagliptin SITAGLIPTIN	2.30 (0.53 to 10.31)	0.43 to 12.48	Unclear
Semaglutide 16 mg injection once weekly SEMA_SC_16MG_QW	4.70 (0.17 to 155)	0.15 to 164	Unclear

Ranking

How likely each treatment is to be among the best. Rankings ignore the size of differences and their certainty, so read them with the effects above.

League table

Every treatment against every other: 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	SEMA_SC_8MG_QW	SEMA_SC_2p0MG_QW	ECNO_SC_1p2MG_QW	ECNO_SC_0p4MG_QW	ECNO_SC_0p8MG_QW	TIRZ_SC_1MG_QW	TIRZ_SC_10MG_QW	TIRZ_SC_15MG_QW	TIRZ_SC_5MG_QW	LIRA_SC_1p8MG_QD	ALBI_SC_FLEX_30-50_QW	DULA_SC_0p75MG_QW	DULA_SC_1p5MG_QW	SEMA_PO_14MG_QD	SEMA_SC_1p0MG_QW	SEMA_PO_7MG_QD	SEMA_PO_3MG_QD	SEMA_SC_0p5MG_QW	SITAGLIPTIN	SEMA_SC_16MG_QW
PLACEBO	PLACEBO	2.48 0.06 to 204	2.42 0.06 to 187	1.57 0.02 to 169	1.55 0.02 to 168	1.53 0.02 to 160	1.47 0.02 to 141	1.45 0.02 to 162	1.44 0.02 to 137	1.43 0.02 to 164	1.37 0.29 to 6.79	1.14 0.50 to 2.56	1.07 0.19 to 7.07	0.81 0.38 to 1.97	0.74 0.20 to 2.52	0.59 0.26 to 1.39	0.58 0.14 to 2.37	0.56 0.13 to 2.29	0.49 0.19 to 1.06	0.43 0.10 to 1.90	0.21 0.01 to 5.73
SEMA_SC_8MG_QW	0.40 0.00 to 16.84	SEMA_SC_8MG_QW	1.03 0.00 to 261	0.60 0.00 to 251	0.59 0.00 to 258	0.59 0.00 to 239	0.57 0.00 to 245	0.56 0.00 to 268	0.56 0.00 to 243	0.56 0.00 to 228	0.54 0.01 to 29.70	0.46 0.01 to 20.88	0.43 0.00 to 27.62	0.33 0.00 to 14.93	0.30 0.00 to 15.16	0.24 0.00 to 10.95	0.23 0.00 to 12.31	0.23 0.00 to 12.78	0.19 0.00 to 8.55	0.18 0.00 to 9.62	0.09 0.00 to 6.62
SEMA_SC_2p0MG_QW	0.41 0.01 to 16.45	0.97 0.00 to 318	SEMA_SC_2p0MG_QW	0.64 0.00 to 258	0.62 0.00 to 244	0.63 0.00 to 246	0.58 0.00 to 202	0.58 0.00 to 231	0.59 0.00 to 235	0.60 0.00 to 262	0.56 0.01 to 32.39	0.47 0.01 to 19.67	0.44 0.00 to 26.99	0.34 0.00 to 14.46	0.31 0.00 to 14.97	0.24 0.00 to 10.34	0.24 0.00 to 12.11	0.23 0.00 to 11.50	0.20 0.00 to 8.18	0.18 0.00 to 10.45	0.09 0.00 to 6.53
ECNO_SC_1p2MG_QW	0.64 0.01 to 50.05	1.66 0.00 to 716	1.55 0.00 to 712	ECNO_SC_1p2MG_QW	0.96 0.00 to 450	0.95 0.00 to 597	0.92 0.00 to 445	0.89 0.00 to 574	0.92 0.00 to 423	0.87 0.00 to 496	0.84 0.01 to 83.35	0.72 0.01 to 60.95	0.69 0.00 to 81.10	0.52 0.00 to 42.67	0.46 0.00 to 42.42	0.37 0.00 to 30.28	0.36 0.00 to 33.19	0.35 0.00 to 33.87	0.30 0.00 to 24.78	0.28 0.00 to 26.72	0.13 0.00 to 31.62
ECNO_SC_0p4MG_QW	0.64 0.01 to 44.54	1.70 0.00 to 658	1.61 0.00 to 707	1.04 0.00 to 533	ECNO_SC_0p4MG_QW	0.98 0.00 to 435	0.92 0.00 to 518	0.97 0.00 to 501	0.95 0.00 to 486	0.94 0.00 to 496	0.89 0.01 to 78.29	0.73 0.01 to 56.18	0.70 0.00 to 73.70	0.52 0.00 to 39.09	0.48 0.00 to 40.27	0.39 0.00 to 29.36	0.37 0.00 to 34.00	0.36 0.00 to 30.58	0.31 0.00 to 23.50	0.28 0.00 to 26.00	0.13 0.00 to 29.24
ECNO_SC_0p8MG_QW	0.65 0.01 to 47.83	1.70 0.00 to 729	1.59 0.00 to 663	1.05 0.00 to 516	1.02 0.00 to 471	ECNO_SC_0p8MG_QW	0.96 0.00 to 511	0.93 0.00 to 505	0.97 0.00 to 480	0.95 0.00 to 616	0.87 0.01 to 85.78	0.72 0.01 to 56.16	0.71 0.00 to 77.45	0.53 0.01 to 43.44	0.47 0.00 to 43.76	0.39 0.00 to 33.27	0.36 0.00 to 34.50	0.35 0.00 to 32.82	0.31 0.00 to 26.73	0.27 0.00 to 27.85	0.14 0.00 to 28.77
TIRZ_SC_1MG_QW	0.68 0.01 to 49.66	1.75 0.00 to 717	1.72 0.00 to 766	1.09 0.00 to 569	1.09 0.00 to 575	1.05 0.00 to 633	TIRZ_SC_1MG_QW	0.98 0.00 to 530	1.00 0.00 to 506	1.00 0.00 to 523	0.95 0.01 to 85.74	0.77 0.01 to 58.95	0.73 0.01 to 77.48	0.55 0.01 to 42.25	0.49 0.00 to 40.97	0.40 0.00 to 30.69	0.39 0.00 to 33.57	0.38 0.00 to 31.46	0.33 0.00 to 26.01	0.29 0.00 to 26.22	0.14 0.00 to 29.60
TIRZ_SC_10MG_QW	0.69 0.01 to 56.73	1.78 0.00 to 855	1.71 0.00 to 788	1.12 0.00 to 499	1.03 0.00 to 562	1.07 0.00 to 550	1.02 0.00 to 502	TIRZ_SC_10MG_QW	0.99 0.00 to 539	1.03 0.00 to 531	0.94 0.01 to 101	0.79 0.01 to 66.98	0.74 0.00 to 90.84	0.56 0.00 to 52.54	0.49 0.00 to 49.45	0.41 0.00 to 35.43	0.38 0.00 to 41.33	0.38 0.00 to 41.21	0.33 0.00 to 28.34	0.29 0.00 to 33.29	0.14 0.00 to 36.10
TIRZ_SC_15MG_QW	0.69 0.01 to 46.52	1.79 0.00 to 792	1.68 0.00 to 734	1.08 0.00 to 681	1.06 0.00 to 596	1.03 0.00 to 615	1.00 0.00 to 522	1.01 0.00 to 504	TIRZ_SC_15MG_QW	1.03 0.00 to 493	0.96 0.01 to 84.90	0.80 0.01 to 54.88	0.74 0.01 to 76.04	0.59 0.01 to 41.03	0.50 0.00 to 39.43	0.41 0.00 to 30.31	0.39 0.00 to 32.71	0.38 0.00 to 32.49	0.34 0.00 to 25.01	0.30 0.00 to 26.47	0.14 0.00 to 36.47
TIRZ_SC_5MG_QW	0.70 0.01 to 47.78	1.78 0.00 to 743	1.67 0.00 to 727	1.15 0.00 to 644	1.06 0.00 to 621	1.05 0.00 to 614	1.00 0.00 to 473	0.97 0.00 to 502	0.97 0.00 to 437	TIRZ_SC_5MG_QW	0.91 0.01 to 83.53	0.77 0.01 to 62.37	0.72 0.00 to 79.98	0.57 0.00 to 42.13	0.49 0.00 to 43.27	0.41 0.00 to 31.69	0.39 0.00 to 33.94	0.38 0.00 to 34.77	0.34 0.00 to 24.39	0.29 0.00 to 27.95	0.13 0.00 to 30.30
LIRA_SC_1p8MG_QD	0.73 0.15 to 3.50	1.86 0.03 to 190	1.77 0.03 to 190	1.19 0.01 to 161	1.12 0.01 to 150	1.15 0.01 to 157	1.06 0.01 to 147	1.07 0.01 to 155	1.04 0.01 to 139	1.10 0.01 to 155	LIRA_SC_1p8MG_QD	0.83 0.14 to 4.67	0.79 0.12 to 5.86	0.60 0.11 to 3.57	0.54 0.13 to 2.20	0.44 0.07 to 2.65	0.42 0.08 to 2.09	0.41 0.08 to 1.98	0.36 0.06 to 2.04	0.32 0.06 to 1.67	0.15 0.00 to 6.21
ALBI_SC_FLEX_30-50_QW	0.88 0.39 to 1.99	2.18 0.05 to 193	2.14 0.05 to 181	1.39 0.02 to 156	1.37 0.02 to 153	1.38 0.02 to 144	1.30 0.02 to 136	1.27 0.01 to 157	1.25 0.02 to 129	1.29 0.02 to 158	1.20 0.21 to 7.13	ALBI_SC_FLEX_30-50_QW	0.93 0.15 to 7.42	0.71 0.24 to 2.56	0.65 0.15 to 2.83	0.52 0.17 to 1.66	0.51 0.10 to 2.60	0.49 0.10 to 2.62	0.43 0.13 to 1.22	0.38 0.07 to 2.23	0.19 0.01 to 5.33
DULA_SC_0p75MG_QW	0.93 0.14 to 5.14	2.31 0.04 to 249	2.29 0.04 to 235	1.46 0.01 to 246	1.43 0.01 to 202	1.41 0.01 to 205	1.38 0.01 to 193	1.35 0.01 to 205	1.35 0.01 to 185	1.39 0.01 to 208	1.27 0.17 to 8.28	1.07 0.13 to 6.74	DULA_SC_0p75MG_QW	0.76 0.10 to 5.08	0.69 0.15 to 2.50	0.55 0.07 to 3.72	0.54 0.12 to 1.97	0.53 0.11 to 2.00	0.45 0.06 to 2.88	0.41 0.08 to 1.74	0.19 0.00 to 8.45
DULA_SC_1p5MG_QW	1.24 0.51 to 2.66	3.07 0.07 to 265	2.94 0.07 to 244	1.94 0.02 to 219	1.92 0.03 to 207	1.89 0.02 to 199	1.81 0.02 to 186	1.80 0.02 to 224	1.70 0.02 to 183	1.77 0.02 to 203	1.67 0.28 to 9.44	1.41 0.39 to 4.21	1.31 0.20 to 10.09	DULA_SC_1p5MG_QW	0.91 0.20 to 3.90	0.73 0.21 to 2.25	0.71 0.14 to 3.57	0.70 0.14 to 3.42	0.60 0.15 to 1.73	0.53 0.10 to 2.97	0.26 0.01 to 8.26
SEMA_PO_14MG_QD	1.35 0.40 to 5.11	3.35 0.07 to 319	3.28 0.07 to 294	2.20 0.02 to 298	2.10 0.02 to 255	2.15 0.02 to 254	2.03 0.02 to 250	2.02 0.02 to 273	2.00 0.03 to 232	2.04 0.02 to 262	1.84 0.46 to 7.99	1.55 0.35 to 6.87	1.44 0.40 to 6.62	1.10 0.26 to 4.98	SEMA_PO_14MG_QD	0.81 0.18 to 3.85	0.78 0.36 to 1.71	0.76 0.35 to 1.65	0.66 0.13 to 3.10	0.59 0.24 to 1.50	0.28 0.01 to 10.55
SEMA_SC_1p0MG_QW	1.69 0.72 to 3.85	4.25 0.09 to 381	4.11 0.10 to 343	2.72 0.03 to 301	2.60 0.03 to 299	2.59 0.03 to 299	2.48 0.03 to 242	2.44 0.03 to 311	2.42 0.03 to 253	2.44 0.03 to 306	2.29 0.38 to 13.63	1.93 0.60 to 5.95	1.80 0.27 to 14.09	1.37 0.44 to 4.82	1.24 0.26 to 5.69	SEMA_SC_1p0MG_QW	0.98 0.18 to 5.23	0.95 0.17 to 5.18	0.83 0.32 to 1.77	0.73 0.13 to 4.23	0.35 0.01 to 10.74
SEMA_PO_7MG_QD	1.73 0.42 to 7.33	4.30 0.08 to 447	4.22 0.08 to 401	2.79 0.03 to 408	2.70 0.03 to 349	2.76 0.03 to 339	2.58 0.03 to 333	2.63 0.02 to 356	2.55 0.03 to 311	2.54 0.03 to 373	2.36 0.48 to 12.09	1.98 0.39 to 9.84	1.84 0.51 to 8.58	1.41 0.28 to 7.31	1.28 0.59 to 2.78	1.03 0.19 to 5.55	SEMA_PO_7MG_QD	0.97 0.47 to 2.10	0.85 0.15 to 4.29	0.76 0.32 to 1.88	0.36 0.01 to 14.39
SEMA_PO_3MG_QD	1.77 0.44 to 7.55	4.39 0.08 to 455	4.33 0.09 to 411	2.87 0.03 to 425	2.77 0.03 to 348	2.82 0.03 to 346	2.64 0.03 to 326	2.63 0.02 to 382	2.62 0.03 to 304	2.66 0.03 to 359	2.43 0.51 to 12.10	2.03 0.38 to 10.43	1.90 0.50 to 8.83	1.44 0.29 to 7.27	1.31 0.61 to 2.84	1.06 0.19 to 5.73	1.03 0.48 to 2.14	SEMA_PO_3MG_QD	0.87 0.15 to 4.48	0.77 0.32 to 1.92	0.38 0.01 to 14.25
SEMA_SC_0p5MG_QW	2.05 0.94 to 5.14	5.26 0.12 to 483	5.13 0.12 to 435	3.31 0.04 to 368	3.21 0.04 to 384	3.22 0.04 to 351	3.07 0.04 to 328	3.01 0.04 to 374	2.97 0.04 to 332	2.95 0.04 to 362	2.80 0.49 to 17.78	2.30 0.82 to 7.98	2.21 0.35 to 17.86	1.65 0.58 to 6.53	1.51 0.32 to 7.64	1.20 0.57 to 3.13	1.18 0.23 to 6.79	1.15 0.22 to 6.87	SEMA_SC_0p5MG_QW	0.89 0.17 to 5.56	0.44 0.01 to 13.14
SITAGLIPTIN	2.30 0.53 to 10.31	5.63 0.10 to 611	5.54 0.10 to 531	3.59 0.04 to 536	3.58 0.04 to 481	3.67 0.04 to 463	3.51 0.04 to 424	3.44 0.03 to 448	3.32 0.04 to 436	3.42 0.04 to 524	3.12 0.60 to 16.70	2.60 0.45 to 13.86	2.44 0.58 to 12.34	1.89 0.34 to 10.30	1.69 0.67 to 4.09	1.36 0.24 to 7.70	1.32 0.53 to 3.14	1.29 0.52 to 3.16	1.13 0.18 to 6.06	SITAGLIPTIN	0.48 0.01 to 18.47
SEMA_SC_16MG_QW	4.70 0.17 to 155	11.53 0.15 to 2555	11.52 0.15 to 2334	7.97 0.03 to 2378	7.59 0.03 to 2335	7.38 0.03 to 2391	7.18 0.03 to 1848	7.29 0.03 to 2392	7.07 0.03 to 2005	7.44 0.03 to 1856	6.50 0.16 to 298	5.40 0.19 to 186	5.16 0.12 to 252	3.82 0.12 to 142	3.51 0.09 to 139	2.83 0.09 to 98.05	2.77 0.07 to 115	2.66 0.07 to 111	2.28 0.08 to 76.62	2.07 0.05 to 86.32	SEMA_SC_16MG_QW

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau): 0.262 (95% CrI 0.069 to 0.829), log scale
Residual deviance: 25.3 for 35 data points
DIC: 44.0 (pD 18.6)
Largest R-hat: 1.001
Smallest ESS: bulk 1,628, tail 2,729
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 25 to 365.26 weeks
NoteOutcome assessment, analysis set: mixed: full_analysis 1, other 1, randomized 1, safety 7
NoteOutcome assessment, definition: mixed: EAC confirmed acute pancreatitis 1, EAC confirmed retinopathy complications: photocoagulation, intravitreal agents, vitreous hemorrhage or diabetes related blindness 1, in trial adverse events related to diabetic retinopathy by MedDRA search 1, not stated 6, severe hypoglycemic events, adverse event of special interest 1
NoteOutcome assessment, adjudicated: mixed: no 1, not stated 4, yes 5
NoteOutcome assessment, intercurrent events (discontinuation): mixed: not stated 8, treatment_policy 1, while_on_treatment 1
NoteOutcome assessment, intercurrent events (rescue): mixed: not stated 9, treatment_policy 1
NoteRisk of bias, blinding: mixed: double_blind 9, single_blind 1
NoteData handling, input conversions: count_from_percent 2, printed_denominator 1

Comparability items per trial
Trial	time weeks	analysis set	definition	instrument	adjudicated	proportion method	intercurrent events (discontinuation)	intercurrent events (rescue)	blinding	funding	start year	Eligibility
NCT03131687	30	safety	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	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
PIONEER 4	57	safety	in trial adverse events related to diabetic retinopathy by MedDRA search	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2016	Age 18 or older; T2D on metformin with or without SGLT2i; HbA1c 7.0 to 9.5 percent; eGFR 60 or more
REWIND	365.26	randomized	not stated	not stated	yes	not stated	treatment_policy	not stated	double_blind	industry	2011	age 50 or older with T2D; HbA1c 9.5 percent or less; BMI 23 or more; CV disease or risk factors
PIONEER 10	57	safety	not stated	not stated	yes	not stated	while_on_treatment	treatment_policy	single_blind	industry	2017	Japanese adults 20 or older; T2D; HbA1c 7.0 to 10.5 percent on one oral glucose lowering drug
PIONEER 12	31	other	EAC confirmed acute pancreatitis	not stated	yes	not stated	not stated	not stated	double_blind	industry	2019	adults with type 2 diabetes on metformin, HbA1c 7.0 to 10.5 percent
NCT02465515	140.89	safety	severe hypoglycemic events, adverse event of special interest	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2015	type 2 diabetes with established cardiovascular disease
NCT05486065	49	safety	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2022	age 18 to 64; HbA1c 7.0 to 10.5; BMI 27 or more; on metformin
SUSTAIN™ 5	35	safety	not stated	not stated	yes	not stated	not stated	not stated	double_blind	industry	2014	age 18 or older (20 in Japan); HbA1c 7.0 to 10.0 percent; stable basal insulin with or without metformin; eGFR 30 or more
SUSTAIN™ 6	109	full_analysis	EAC confirmed retinopathy complications: photocoagulation, intravitreal agents, vitreous hemorrhage or diabetes related blindness	not stated	yes	not stated	not stated	not stated	double_blind	industry	2013	T2D HbA1c 7.0 or more; age 50 or more with CVD, CHF or CKD stage 3 or more, or age 60 or more with CV risk factor
S002947	25	safety	not stated	not stated	no	not stated	not stated	not stated	double_blind	industry	2021	age 18 to 65; HbA1c 7.0 to 10.5 percent; BMI 20 to 35; diet or one oral agent washed out

Trial data

What each trial contributes. Arm rows give the arm value with its standard error, or events over participants; contrast rows give the 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
NCT03131687	A1	PLACEBO	30	arm, events	0 / 51		R0016215:Results
NCT03131687	A2	TIRZ_SC_1MG_QW	30	arm, events	0 / 53		R0016215:Results
NCT03131687	A3	TIRZ_SC_5MG_QW	30	arm, events	0 / 55		R0016215:Results
NCT03131687	A4	TIRZ_SC_10MG_QW	30	arm, events	0 / 52		R0016215:Results
NCT03131687	A5	TIRZ_SC_15MG_QW	30	arm, events	0 / 53		R0016215:Results
NCT03131687	A6	DULA_SC_1p5MG_QW	30	arm, events	0 / 54		R0016215:Results
PIONEER 4	A1	SEMA_PO_14MG_QD	57	arm, events	8 / 285		R0015836:Supplement Table S7
PIONEER 4	A2	LIRA_SC_1p8MG_QD	57	arm, events	4 / 284		R0015836:Supplement Table S7
PIONEER 4	A3	PLACEBO	57	arm, events	2 / 142		R0015836:Supplement Table S7
REWIND	A1	PLACEBO	365.26	arm, events	76 / 4,952		R0018537:Table 2
REWIND	A2	DULA_SC_1p5MG_QW	365.26	arm, events	95 / 4,949		R0018537:Table 2
PIONEER 10	A1	SEMA_PO_3MG_QD	57	arm, events	9 / 131		R0018421:Table 2
PIONEER 10	A2	SEMA_PO_7MG_QD	57	arm, events	12 / 132		R0018421:Table 2
PIONEER 10	A3	SEMA_PO_14MG_QD	57	arm, events	7 / 130		R0018421:Table 2
PIONEER 10	A4	DULA_SC_0p75MG_QW	57	arm, events	3 / 65		R0018421:Table 2
PIONEER 12	A1	SEMA_PO_3MG_QD	31	arm, events	17 / 361		R0019776:Results
PIONEER 12	A2	SEMA_PO_7MG_QD	31	arm, events	13 / 360		R0019776:Results
PIONEER 12	A3	SEMA_PO_14MG_QD	31	arm, events	12 / 361		R0019776:Results
PIONEER 12	A4	SITAGLIPTIN	31	arm, events	20 / 359		R0019776:Results
NCT02465515	A1	PLACEBO	140.89	arm, events	89 / 4,732		registry:outcomes
NCT02465515	A2	ALBI_SC_FLEX_30-50_QW	140.89	arm, events	78 / 4,731		registry:outcomes
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	1 / 62		R0005510:Table 2
NCT05486065	A4	PLACEBO	49	arm, events	0 / 60		R0005510:Table 2
SUSTAIN™ 5	A1	SEMA_SC_0p5MG_QW	35	arm, events	4 / 132	count_from_percent	R0012671:Results
SUSTAIN™ 5	A2	SEMA_SC_1p0MG_QW	35	arm, events	1 / 132	count_from_percent	R0012671:Results
SUSTAIN™ 5	A3	PLACEBO	35	arm, events	0 / 133		R0012671:Results
SUSTAIN™ 6	A1	SEMA_SC_0p5MG_QW	109	arm, events	25 / 826		R0020578:Results
SUSTAIN™ 6	A2	SEMA_SC_1p0MG_QW	109	arm, events	25 / 822		R0020578:Results
SUSTAIN™ 6	A6	PLACEBO	109	arm, events	29 / 1,649	printed_denominator	R0020578:Results
S002947	A1	ECNO_SC_0p4MG_QW	25	arm, events	0 / 37		R0006482:Results
S002947	A2	ECNO_SC_0p8MG_QW	25	arm, events	0 / 36		R0006482:Results
S002947	A3	ECNO_SC_1p2MG_QW	25	arm, events	0 / 36		R0006482:Results
S002947	A4	PLACEBO	25	arm, events	0 / 36		R0006482:Results

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