Table 3.

Clinical trials of GLP1 receptor agonists, DPP4 inhibitors, and SGLT2 inhibitors in children and adolescents with type 2 diabetes. List of all ongoing (in italics) and completed trials of GLP1 receptor agonists, DPP4 inhibitors, and SGLT2 inhibitors in children and adolescents < 18 years in the USA. Participant numbers listed in parentheses indicate target enrollment numbers for ongoing trials

Drug class	Experimental drug	Design	Ph	N	Duration	Primary and secondary outcomes	Mortality and SAE	Results
GLP1RA	Liraglutide NCT02960659	Randomized Open label	1	(102)	12 wk	1) Change in stool short chain fatty acids, change in gluconeogenesis 2) Change in glucose production, change in gut microbiota diversity	Ongoing study	Estimated completion: 2022
	NCT01541215	Randomized Double blind	3	135	26 wk + 26 wk open-label extension	1) Change in HbA1c from baseline to wk 26 2) Various related to glycemic control, biochemistry, development, AE	Mortality: none SAE: placebo 4/68, liraglutide during treatment 9/66, liraglutide during f/u 7/52	Completed: 2020 Results: [76]
	NCT00943501	Randomized Double blind	1	21	5 wk + 3 wk AE f/u	1) Number and type of AE 2) PK, PD	Mortality: none SAEs: none	Completed: 2011 Results: [77, 78]
	Dulaglutide NCT02963766	Randomized Double blind	3	154	60 wk	1) Change in HbA1c from baseline to wk 26 2) Various related to glycemic control, AE, PK	Ongoing study	Estimated completion: 2022
	Exenatide NCT01554618	Randomized Quadruple blind	3	84	24 wk + 28 wk open-label extension	1) Change in HbA1c from baseline to wk 24, AE, ADA 2) Various related to glycemic control, biochemistry, AE, PK	Ongoing study	Estimated completion: 2023
	NCT00658021	Randomized Double blind	3	122	28 wk	1) Change in HbA1c from baseline to wk 28, AESI 2) Various related to glycemic control, biochemistry	Mortality: none SAE: 5 μg 3/41, 10 μg 1/37, placebo 1/42	Completed: 2020 Results: not published
	NCT00950677	Randomized Single blind	4	16	4 h	1) Glucose concentration and AUC 2) Glucagon, gastric emptying, PK	Not available	Completed: 2011 Results: not published
	NCT00254254	Randomized Single blind	2	13	1d per treatment (× 3)	1) PK, PD, AE	Mortality: none SAE: 1/13	Completed: 2007 Results: [79]
	Lixisenatide NCT02803918	Randomized Double blind	1	23	6 wk + 4 wk f/u	1) AE, TEAE, ADA 2) PK, PD	Not available	Completed: 2020 Results: not published
	NCT01572649	Randomized Double blind	1	24ǂ	1d per treatment (× 3)	1) Plasma glucose AUC 2) PK, PD	Not available	Completed: 2014 Results: not published
	Semaglutide NCT04596631	Randomized Quadruple blind	3	(132)	52 wk	1) Change in HbA1c baseline to wk 26 2) Various related to glycemic control, weight, metabolic, biochemistry, development	Ongoing study	Estimated completion: 2025
DPP4i	Alogliptin NCT02856113	Randomized Quadruple blind	3	(150)	52 wk	1) Change in HbA1c from baseline to wk 26 2) Various related to safety	Ongoing study	Estimated completion: 2021
	NCT00957268	Non-randomized Open label	1	24†	72 h	1) PK 2) PK, PD	Mortality: none SAE: none	Completed: 2013 Results: not published
	Linagliptin NCT03429543	Randomized Double blind	3	(186)	26 wk + 26 wk safety extension	1) Change in HbA1c baseline to wk 16, treatment failure at wk 26 2) Various related to glycemic control, metabolic	Ongoing study	Estimated completion: 2023
	NCT01342484	Randomized Double blind	2	40	12 wk	1) Change in HbA1c from baseline to wk 12 2) % DPP4 inhibition, FPG	Mortality: none SAE: placebo 1/15, linagliptin 1 mg 0/10, linagliptin 5 mg 0/14	Completed: 2016 Results: [80]
	Saxagliptin NCT03199053	Randomized Double blind	3	(254)	52 wk	1) Change in HbA1c from baseline to wk 26 2) FPG, HbA1c	Ongoing study	Estimated completion: 2023
	NCT01204775	Randomized Double blind	3	8	52 wk	1) Change in HbA1c from baseline to wk 16	Mortality: none SAE: placebo 1/4, saxagliptin 0/4	Completed: 2016 Results: NCT01204775
	NCT01434186	Randomized Double blind	3	6	52 wk	1) Change in HbA1c from baseline to wk 16	Mortality: none SAE: none	Completed: 2016 Results: NCT01434186
	Sitagliptin NCT01485614	Randomized Double blind	3	200	20 wk placebo-controlled then 34 wk active-controlled	1) Change in HbA1c from baseline to wk 20, AE 2) Various related to glycemic control, metabolic, biochemistry, development	Mortality: 1 in sitagliptin group SAE: sitagliptin 10/95, placebo/metformin 7/90, metformin 1/9, placebo/sitagliptin 3/5	Completed: 2019 Results: NCT01485614
	NCT00730275	Randomized Double blind	1	35	72 h + 10–14d AE f/u	1) AE, sitagliptin AUC 2) PK, PD	Mortality: none SAE: none	Completed: 2019 Results: [81]
	Sitagliptin/metformin XR combined NCT01557504	Randomized Open label	1	25	9d + 14d AE f/u	1) Ability to swallow medication, PK, PD	Mortality: none SAE: none	Completed: 2014 Results: NCT01557504
SGLT2i	Canagliflozin NCT03170518	Randomized Double blind	3	(146)	26 wk	1) Change in HbA1c from baseline to wk 26 2) FPG, HbA1c, rescue therapy, body weight, biochemistry, development, UACR	Ongoing study	Estimated completion: 2023
	NCT02000700	Non-randomized Open label	1	17	14d	1) Plasma concentration of drug after multiple doses 2) Plasma glucose, glucose excretion, tablet acceptability, AE	Not available	Completed: 2016 Results: not published
	Dapagliflozin NCT03199053	Randomized Double blind	3	(254)	52 wk	1) Change in HbA1c from baseline to wk 26 2) FPG, HbA1c	Ongoing study	Estimated completion: 2023
	NCT02725593	Randomized Double blind	3	72	24 wk + 28 wk safety extension	1) Change in HbA1c from baseline to wk 24 2) FPG, rescue medication, HbA1c	Mortality: none SAE: 10 mg/10 mg 2/39, placebo/10 mg 3/33	Completed: 2020 Results: NCT02725593
	NCT01525238	Randomized Open label	1	24	48 h	1) PK 2) PK, various related to glycemic control, safety	Mortality: none SAE: none	Completed: 2014 Results: [82]
	Empagliflozin NCT03429543	Randomized Double blind	3	(186)	26 wk + 26 wk safety extension	1) Change in HbA1c baseline to wk 16, treatment failure at wk 26 2) Various related to glycemic control, metabolic	Ongoing study	Estimated completion: 2023
	NCT02121483	Randomized Open label	1	27	3d	1) PK 2) Urinary glucose excretion, FPG, plasma glucose profile	Mortality: none SAE: none	Completed: 2016 Results: [83, 84]
	Ertugliflozin NCT04029480	Randomized Double blind	3	(150)	54 wk	1) Change in HbA1c from baseline to wk 24, AEs 2) HbA1c, FPG	Ongoing study	Estimated completion: 2025

Abbreviations: ADA, anti-drug antibodies; AE, adverse events; AESI, adverse events of special interest; AUC, area under the curve; d, days; FPG, fasting plasma glucose; h, hours; PD, pharmacodynamics; PK, pharmacokinetics; Ph, phase; SAE, serious adverse events; TEAE, treatment-emergent adverse events; wk, weeks

^ǂNCT01572649 enrolled 24 participants but not all were < 18y (at least 3 patients below 15 years and no more than 3 patients aged between 16 and 18 years)

^†NCT00957268 enrolled 46 participants but only 24 were < 18y