Pharmacological management of type 2 diabetes mellitus in children and adolescents: A systematic review and network meta-analysis

Table 1 Characteristics of included studies

Ref.	Year	Blinding setting	Study period (weeks)	Interventions	Sample	Mean age (years)	Baseline HbA1c (%)	Baseline weight (kg)	Baseline BMI (kg/m2)	Baseline TC (mg/dL)	Baseline TG (mg/dL)	Baseline HDL (mg/dL)	Baseline LDL (mg/dL)
Gottschalk et al[13]	2007	Single blind	24	Glimepiride	132	13.8 ± 2.3	8.52 ± 1.58	82.60 ± 25.60	31.57 ± 8.48
				Metformin	131	13.8 ± 2.3	8.54 ± 1.57	83.83 ± 27.47	31.60 ± 8.17
Tamborlane et al[20]	2018	Double blind	12	Linagliptin-1 mg	10	14.0 ± 1.9	8.22 ± 0.93	75.3 ± 19.3	28.0 ± 5.2
				Linagliptin-5 mg	14	14.3 ± 2.1	7.87 ± 0.98	84.8 ± 25.1	33.0 ± 8.0
				Placebo	15	13.7 ± 2.0	7.60 ± 0.92	78.2 ± 21.8	29.2 ± 6.0
Tamborlane et al[18]	2019	Double blind	26	Liraglutide + metformin	66	14.57 ± 1.73	7.87 ± 1.35	93.3 ± 31.0	34.55 ± 10.87
				Metformin	68	14.57 ± 1.73	7.69 ± 1.34	89.8 ± 22.1	33.27 ± 7.36
Tamborlane et al[19]	2022	Double blind	24	Dapagliflozin 10 mg	39	16.1 ± 3.3	7.95 ± 1.59	89.2 ± 25.7	31.3 ± 7.5
				Placebo	33	16.2 ± 3.6	7.85 ± 1.19	92.5 ± 31.9	33.6 ± 8.8
Tamborlane et al[15]	2022	Double blind	24	Exenatide -2 mcg	58	14.9 ± 1.88	8.13 ± 1.2	102.18 ± 30.1	36.86 ± 9.28	167.44 ± 42.54	161.2 ± 104.52	41.76 ± 12.76	94.74 ± 36.74
				Placebo	24	15.6 ± 1.66	8.28 ± 1.5	96.7 ± 22.7	35.14 ± 6.58
Jalaludin et al[22]	2022	Double blind	54	Sitagliptin 100 mg + metformin	107	14.4 ± 2.2	8.0 ± 1.1	81.9 ± 25.4	31.2 ± 8.1
				Metformin	113	13.9 ± 1.8	8.1 ± 1.1	79.8 ± 24.8	30.6 ± 8.5
Shankar et al[14]	2022	Double blind	54	Sitagliptin	95	14.3 ± 2.0	7.4 ± 1.0	89.1 ± 25.3	33.3 ± 7.7
				Placebo	95	13.7 ± 1.9	7.6 ± 1.1	81.9 ± 24.8	31.2 ± 7.7
Arslanian et al[16]	2022	Double blind	26	Dulaglutide 0.75 mg	51	14.7 ± 2.21	7.92 ± 1.27	90 ± 28.3	33.6 ± 9	164.5	167.5	40.9	91.4
				Dulaglutide 1.5 mg	52	14.7 ± 1.8	8.16 ± 1.39	92.6 ± 21.6	34.3 ± 7	166.1	162.7	41.8	95.3
				Placebo	51	14.2 ± 2.1	8.14 ± 1.12	88.9 ± 29.4	34.3 ± 10.2	169.9	189.4	41.8	93.5
Laffel et al[21] (DINAMO)	2023	Double blind	26	Empagliflozin 10 mg	52	14.4 ± 1.9	8.0 ± 1.29	98.66 ± 24.35	35.54 ± 7.17
				Linagliptin 5 mg	52	14.6 ± 1.9	8.05 ± 1.11	102.76 ± 26.40	35.55 ± 7.55
				Placebo	53	14.6 ± 1.8	8.05 ± 1.23	96.38 ± 29.55	33.3 ± 7.7
Shehadeh et al[22](T2N OW)	2023	Double blind	26	Dapagliflozin 5 mg	81	14.4 ± 2.0	8.22 ± 1.46	78.8 ± 18.1	Z-score 17 ± 0.7
				Saxagliptin 2.5 mg	88	14.5 ± 1.8	8.02 ± 1.43	82.5 ± 24.0	Z-score 18 ± 0.7
				Placebo	76	14.7 ± 1.6	7.96 ± 1.63	76.2 ± 23.1	Z-score 15 ± 0.8
NCT00658021[24]	2020	Double blind	28	Exenatide 5 mcg BD	40	13.7 ± 1.94	NR (HbA1 range: 6.5 - 10.5)	NR	NR
				Exenatide 10 mcg BD	38	14.0 ± 1.95	NR	NR	NR
				Placebo	42	14.4 ± 1.82	NR	NR	NR
Dietsche et al[23]	2023	Open label	12	Liraglutide+ metformin	11	15.0 ± 2.1	7.3 ± 0.8	114 ± 24.4	38.6 ± 8.3
				Metformin	13	15.6 ± 2.1	6.3 ± 0.8	117 ± 25.0	41.1 ± 7.6
Studies excluded from meta-analysis of primary outcomes
RISE[29]	2019	Open label	52	Insulin then metformin	44	14.9 ± 2.0	5.7 ± 0.6	102.0 ± 25.7	36.5 ± 6.4		98.32	38.67 ± 11.6	88.94 ± 30.94
				Metformin	47	13.9 ± 2.1	5.7 ± 0.6	97.7 ± 23.3	36.9 ± 6.4		103.63	38.67 ± 7.73	81.21 ± 23.2
Wheeler et al[28]	2018	Open label	26	Insulin determir + metformin	20	15 ± 2.1	8.72 ± 0.86	75.9 ± 16.6	28.7 ± 4.8
				NPH insulin + metformin	22	15 ± 2.2	8.95 ± 1.05	73.2 ± 23.4	27.7 ± 6.6
Jones et al[26]	2002	Double blind	8	Metformin	42	13.9 ± 1.8	8.3 ± 1.3	92.8 ± 31.8	34.2 ± 10.6	174.0 ± 38.67	150.57 ± 115.1	42.5 ± 11.6	100.5 ± 30.9
				Placebo	40	13.6 ± 1.8	9.0 ± 1.4	90.3 ± 38.1	33.9 ± 12.7	189.5 ± 38.67	203.7 ± 194.9	42.5 ± 11.6	112.1 ± 27.1
Klein et al[25]	2014	Double blind	5	Liraglutide	14	14.4 ± 2.2	8.3 ± 1.4	112.7 ± 37.3	40 ± 10.3	165.12 ± 39.06	153.1 ± 97.35	39.44 ± 9.28	95.51 ± 27.84
				Placebo	7	15.6 ± 2.1	7.8 ± 0.9	114.2 ± 34.7	39.9 ± 6.8	185.61 ± 33.26	176.99 ± 85.84	39.44+8.89	110.98 ± 27.84
Barrientos-Pérez et al[27]	2022	Double blind	6	Lixisenatide	18	15.6 ± 1.0	8.16 ± 0.93	91.3 ± 18.8	33.2 ± 4.8
				Placebo	5	15.4 ± 1.5	8.14 ± 1.58	98 ± 14.7	37.4 ± 3.6

HbA1c: Glycated hemoglobin; BMI: Body mass index; TC: Total cholesterol; TG: Triglycerides; HDL: High density lipoprotein; LDL: Low-density lipoprotein.