Overview of Clinical Trials on Type 2 Diabetes Mellitus: A Comprehensive Analysis of the ClinicalTrials.gov Database

Figures & data

Figure 1 Flow chart of trial selection.

Figure 2 Distribution of the eligible clinical trials according to the registered year.

Table 1 Characteristics of Interventional and Observational Trials

Characteristics	Interventional Trials (n=4323)	Observational Trials (n=794)	P-value
Participant			<0.001
Adults and children^a	144 (3.3%)	176 (22.2%)
Only adults	4179 (96.7%)	618 (77.8%)
Sample size			<0.001
≤50	1584 (36.6%)	138 (17.4%)
51–100	808 (18.7%)	83 (10.5%)
101–200	639 (14.8%)	83 (10.5%)
> 200	1280 (29.6%)	489 (61.6%)
NA	12 (0.3%)	1 (0.1%)
Registered after recruitment			<0.001
No	1436 (33.2%)	188 (23.7%)
Yes	2887 (66.8%)	606 (76.3%)
Intervention or exposure^b			<0.001
Drugs	2720 (63.3%)	289(52.6%)
Surgery	67 (1.6%)	28 (5.1%)
Education or lifestyle intervention	934 (21.7%)	83 (15.1%)
Dietary Supplement	294 (6.8%)	9 (1.6%)
Device	220 (5.1%)	47 (8.6%)
Stem cell therapy	16 (0.4%)	1 (0.2%)
Others	46 (1.1%)	92(16.8%)
Region			<0.001
US/Canada	1871 (43.3%)	190 (23.9%)
Europe	1180 (27.3%)	317 (39.9%)
Asia	961 (22.3%)	230 (29.0%)
Others	308 (7.1%)	57 (7.2%)
Center			<0.001
Single-center	2425 (56.1%)	526 (66.2%)
Multi-center	1466 (33.9%)	165 (20.8%)
NA	432 (10.0%)	103 (13.0%)
Funder			<0.001
Industry	2357 (54.5%)	367 (46.2%)
NIH	182 (4.2%)	38 (4.8%)
Others	1784 (41.3%)	389 (49.0%)
Primary completed studies			<0.001
No	421 (9.7%)	118 (14.9%)
Yes	3902 (90.3%)	676 (85.1%)
Results of primary completed studies^c			<0.001
No results available	2788 (71.5%)	620 (91.7%)
Results available	1114 (28.5%)	56 (8.3%)
Study completion			<0.001
Completed	3600 (83.3%)	619 (78.0%)
Ongoing	723 (16.7%)	175 (22.0%)
Publication^d			<0.001
No publication	2455 (68.2%)	498 (80.5%)
Published	1145 (31.8%)	121 (19.5%)

Notes: ^aThe participants of trials included both adults and children; ^bThe trials without available data were not included in the analysis; ^cThe sum of number was the number of primary completed trials; ^dThe sum of number was the number of completed trials.

Abbreviations: NA, not available; NIH, National Institutes of Health.

Table 2 Trend of Changes in the Characteristics of Interventional Trials Registered Between Two Temporal Subsets

Characteristics	Registered Between 2004 and 2011 (n=1987)	Registered Between 2012 and 2019 (n= 2336)	P-value
Registered after recruitment			<0.001
No	395 (19.9%)	1041 (44.6%)
Yes	1592 (80.1%)	1295 (55.4%)
Sample size			<0.001
≤50	671 (33.8%)	913 (39.1%)
51–100	339 (17.1%)	469 (20.1%)
101–200	287 (14.4%)	352 (15.1%)
> 200	678 (34.1%)	602 (25.8%)
NA	12 (0.6%)	0
Purpose			<0.001
Treatment	1539 (77.5%)	1551 (66.4%)
Diagnosis or screening	25 (1.3%)	54 (2.3%)
Supportive care	53 (2.7%)	141 (6.0%)
Health service or preventive	133 (6.7%)	251 (10.7%)
Basic science	120 (6.0%)	208 (8.9%)
NA	117 (5.9%)	131 (5.6%)
Phase^a			<0.001
Phase 1	325 (21.4%)	271 (21.1%)
Phase 1/2	35 (2.3%)	24 (1.9%)
Phase 2	298 (19.6%)	208 (16.2%)
Phase 2/3	43 (2.8%)	27 (2.1%)
Phase 3	505 (33.2%)	359 (27.9%)
Phase 4	315 (20.7%)	398 (30.9%)
Allocation			<0.001
Non-randomized	125 (6.3%)	263 (11.3%)
Randomized	1862 (93.7%)	2073 (88.7%)
Blinding^a			<0.001
Blind	1073 (54.4%)	1186 (50.8%)
Open label	898 (45.6%)	1150 (49.2%)
Region			<0.001
US/Canada	962 (48.4%)	909 (38.9%)
Europe	546(27.5%)	634 (27.1%)
Asia	352 (17.7%)	609 (26.1%)
Others	127 (6.4%)	184 (7.9%)
Center			<0.001
Single-center	1006 (50.6%)	1419 (60.7%)
Multi-center	768 (38.7%)	698 (29.9%)
NA	213 (10.7%)	219 (9.4%)
Funder			<0.001
Industry	1305 (65.7%)	1052 (45.0%)
NIH	97 (4.9%)	85 (3.6%)
Others	585 (29.4%)	1199 (51.3%)

Note: ^aThe trials without available data were not included in the analysis.

Abbreviations: NA, not available; NIH, National Institutes of Health.

Figure 3 Distribution of the common antidiabetic drugs studied in all T2DM-related clinical trials (A) and in T2DM-related intervention trials (B) between two temporal subsets (2004–2011 and 2012–2019). The sum of the percentages may exceed 100% as categories were not mutually exclusive.

Abbreviations: DPP-4, dipeptidyl peptidase-4; GLP-1RAs, glucagon-like peptide-1 receptor agonists; SGLT-2, sodium glucose cotransporter-2; TZDs, thiazolidinediones; AGIs, α-glucosidase inhibitors.

Table 3 Characteristics of Completed Interventional Trials According to the Publication Status^a

Characteristics	Unpublished (n=2455)	Published (n=1145)	P-value
Sample size			<0.001
≤50	1021 (41.6%)	332 (29.0%)
51–100	482 (19.6%)	158 (13.8%)
101–200	370 (15.1%)	150 (13.1%)
> 200	570 (23.2%)	505 (44.1%)
NA	12 (0.5%)	0
Phase^b			<0.001
Phase 1	472 (28.5%)	80 (9.6%)
Phase 1/2	37 (2.2%)	13 (1.6%)
Phase 2	321 (19.4%)	143 (17.1%)
Phase 2/3	35 (2.1%)	29 (3.5%)
Phase 3	424 (25.6%)	355 (42.5%)
Phase 4	368 (22.2%)	215 (25.7%)
Allocation			<0.001
Non-randomized	256 (10.4%)	47 (4.1%)
Randomized	2199 (89.6%)	1098 (95.9%)
Blinding			0.010
Blind	1274 (51.9%)	655 (57.2%)
Open label	1168 (47.6%)	486 (42.4%)
NA	13 (0.5%)	4 (0.3%)
Purpose			0.016
Treatment	1752 (71.4%)	880 (76.9%)
Diagnosis or screening	48 (1.9%)	11 (1.0%)
Supportive care	106 (4.3%)	39 (3.4%)
Health service or preventive	199 (8.1%)	87 (7.6%)
Basic science	202 (8.2%)	72 (6.3%)
NA	148 (6.0%)	56 (4.9%)
Results of primary completed studies			<0.001
No results available	1856 (75.6%)	633 (55.3%)
Results available	599 (24.4%)	512 (44.7%)
Outcome
Negative	–	197 (17.2%)	–
Positive	–	948 (82.8%)
Region			<0.001
US/Canada	1034 (42.2%)	541 (47.2%)
Europe	671 (27.4%)	329 (28.7%)
Asia	578 (23.6%)	200 (17.5%)
Others	170 (6.9%)	75 (6.6%)
Center			<0.001
Single-center	1386 (56.5%)	534 (46.6%)
Multi-center	795 (32.4%)	498 (43.5%)
NA	274 (11.2%)	113 (9.9%)
Funder			0.071
Industry	1445 (58.9%)	703 (61.4%)
NIH	88 (3.6%)	52 (4.5%)
Others	922 (37.6%)	390 (34.1%)
Registered after recruitment			0.011
No	679 (27.7%)	364 (31.8%)
Yes	1776 (72.3%)	781 (68.2%)
Study duration (month)	16.2 (8.9,28.4)	20.3 (13.2,32.5)	<0.001
Duration of primary completion(month)	15.2 (8.1,25.4)	18.3 (12.2,28.9)	<0.001

Notes: ^aPublication statuses of the trials were searched through PubMed and Google Scholar and updated and finalized by July 5, 2020; ^bThe trials without available data were not included in the analysis.

Abbreviations: NA, not available; NIH, National Institutes of Health.

Figure 4 Cumulative publication rate curve since trial primary completion. Kaplan–Meier analysis was used. Trials with a “completed” status were included in the analysis.