Role of automated insulin delivery in managing insulin-treated outpatients with type 2 diabetes: A systematic review and meta-analysis

Table 1 Baseline characteristics of individual randomized trials and study participants included in the meta-analysis

Ref.	Trial design, Trial reg number	Major inclusion criteria	Groups	Interventions	Number	Age (years), mean ± SD	HbA1c (%), mean ± SD	Diabetes duration (years), mean ± SD/median (interquartile range)	Key outcomes	Duration
Borel et al[23], 2024, three hospitals in France	Cross-over, NCT05369871	Age > 18 years, body weight ≤ 150 kg, insulin pump for ≥ 6 months, equipped with a CGM or flash glucose monitoring system, TDDI < 160 U/24 hours, and HbA1c < 10%	AID	DBLG1 hybrid closed-loop system (Accu-Chek Insight insulin pump, DexcomG6 CGM system and Diabeloop application)	17	63 ± 9	7.9 ± 0.9	24 ± 9	TIR, TAR, TBR, coefficient of glucose variation, TDDI, glucose management indicator	13 weeks (including two therapy: 6 weeks therapy of hybrid closed loop and 6 weeks of CSII + CGM)
			Control	Usual insulin pump therapy equipped with a DexcomG6 CGM system (CSII + CGM)	17
Boughton et al[24], 2021, two centers in United Kingdom and Switzerland	Cross-over, NCT04025775	Age ≥ 18 years, subcutaneous insulin therapy and end-stage renal disease requiring maintenance dialysis (hemodialysis or peritoneal dialysis)	AID	CamAPS HX closed-loop app (CamDiab) (Dana Diabecare RS pump, Dexcom G6 CGM system and Cambridge adaptive model predictive control algorithm, version 0.3.71)	26	68.3 ± 11.2	7.2 ± 1.3	20 ± 10	TIR, TAR, TBR, coefficient of glucose variation, TDDI, AEs	40 days (two therapy: 20 days therapy of closed loop and standard insulin therapy)
			Control	Standard subcutaneous insulin therapy with masked CGM	26
Daly et al[25], 2023, two centers in United Kingdom	Cross-over, NCT04701424	Age ≥ 18 years, subcutaneous insulin therapy, HbA1c ≤ 11%	AID	CamAPS HX Closed-loop (Dana insulin pump, Dexcom G6 real-time CGM system, and CamAPS HX Application v.0.3.71)	26	59 ± 11	9.0 ± 1.4	17.5 ± 8.2	TIR, TAR, TBR, HbA1c, mean sensor glucose, coefficient of glucose variation, TDDI, AEs	16 weeks (two therapy: 8 weeks therapy of closed loop and standard insulin therapy)
			Control	MDI and Dexcom G6 CGM system	26
Kudva et al[26], 2025, 21 centers in the United States and Canada	Parallel group, NCT05785832	Age ≥ 18 years, T2D ≥ 6 months. On MDI or insulin pump for ≥ 3 months1	AID	T: Slim X2 insulin pump with CIQ + technology (Tandem) and Dexcom G6 CGM system	215	59 ± 12	8.2 ± 1.4	18 (11-26)	HbA1c, TIR, TAR, TBR, AEs	13 weeks
			Control	Pretrial insulin delivery regimen and Dexcom G6 CGM system	104	57 ± 12	8.1 ± 1.2	18 (11-24)
Reznik et al[27], 2014, 36 centers in Canada, Europe, Israel, South Africa, and the United States	Parallel group, NCT01182493	Age 30-75 years, on MDI, TDDI ≤ 220 U/24 hours, HbA1c 8%-12%, ≥ 2.5 SMBG/day on average	AID	Medtronic MiniMed Paradigm Veo system; Medtronic	168	55.5 ± 9.7	9.0 ± 0.8	14.9 ± 8	HbA1c, mean 24-hour glucose concentrations, area under the curve for hypoglycaemia and hyperglycaemia, TAR, TBR, AEs	6 months
			Control	MDI with SMBG	163	56.4 ± 9.5	9.0 ± 0.8	15.3 ± 8
Reznik et al[28], 2024, muti-center in France	Parallel group, NCT04233229	Age > 18 years, T2D ≥ 6 months. On MDI ≥ 6 months. Requiring nursing support at home, HbA1c 8%-12%	AID	T: Slim X2 insulin pump with CIQ technology (Tandem) and Dexcom G6 CGM system	14	69.3 ± 6.7	9.0 ± 1.2	20.4 ± 12.3	TIR, TAR, TBR, coefficient of glucose variation, HbA1c, TDDI, body weight, body mass index, AEs	12 weeks
			Control	MDI with SMBG (from day 70 onwards, Dexcom G6 CGM until the planned completion of the study at day 90)	15	69.7 ± 10.3	9.25 ± 1.0	17.0 ± 9.05

¹In both groups, 96% were on multiple daily insulin injection and 4% were on an insulin pump.

AEs: Adverse events; AID: Automated insulin delivery; CGM: Continuous glucose monitoring; CIQ: Control-IQ; CSII: Continuous subcutaneous insulin infusion; HbA1c: Glycated hemoglobin; MDI: Multiple daily insulin injection; SMBG: Self-monitoring of blood glucose; TAR: Time above range; TBR: Time below range; TDDI: Total daily dose of insulin; TIR: Time in range; T2D: Type 2 diabetes.

Table 2 Baseline characteristics of individual single-arm studies and study participants included in the meta-analysis

Ref.	Key inclusion criteria	Study type	Number	Baseline HbA1c (%)	Previous insulin delivery method (%)	Closed-loop system used in the study	Study period	Key findings
Bhargava et al[29], 2025, NCT05238142, United States	T2D for ≥ 2 years; using either MDI or CSII pump therapy, with or without CGM for ≥ 3 months; HbA1c < 10%	Prospective	95	7.9 ± 1.0	MDI (61.1), CSII with CGM (20.0), CSII (9.5), AID pump (7.4), other (2.1)	MiniMed 780G advanced hybrid closed-loop	90 days	No severe hypoglycemia, severe hyperglycemia, diabetic ketoacidosis, or hyperglycemic hyperosmolar state events and no device-related serious or unanticipated adverse device effects. Significant CFB in HbA1c (-0.7%), TIR (7.2%), TAR > 10 mmol/L (-7.1%), TAR > 13.9 mmol/L (-1.7%), mean SG: -0.51 mmol/L, SD of SG: -0.08 mmol/L, TDDI: 13.9 U. No significant CFB in TBR < 3.9 mmol/L or < 3 mmol/L, CV of SG
Telci Caklili et al[30], 2024, Turkey	Age ≥ 60 years, brittle diabetes, and a follow-up of ≥ 3 months with an AID system	Retrospective cohort	34	9.4 ± 2.1	MDI (100)	Medtrum A7 + Touchcare patch pump and integrated A7 + CGM and Medtronic 780G	6 months	Significant CFB in HbA1c (-2.07%), TDDI: -10.77 U. At the end of the study after AID use: TIR (64.8%), TAR > 10 mmol/L (26.7%), TAR > 13.9 mmol/L (6.7%), TBR < 3.9 mmol/L (1.8%), TBR < 3 mmol/L (0.5%)
Davis et al[31], 2023, NCT04617795, United States	Age 18-75 years, on basal-bolus or basal only insulin regimen, has no insulin pump within 3 months of screening, HbA1c 8%-12%	Prospective	24	9.4 ± 0.9	BBI (50), basal only insulin (50)	Omnipod 5, Dexcom G6, and Omnipod 5 app on a locked-down. Android phone	8 weeks	Significant CFB in HbA1c (-1.3%), TIR (21.9%), TAR > 10 mmol/L (-21.4%), TAR > 13.9 mmol/L (-16.9%), TAR > 20 mmol/L (-9.2%), mean SG: -1.83 mmol/L, TBR < 3.9 mmol/L (-0.08%), SD of SG: -0.61 mmol/L. No significant CFB in TBR < 3 mmol/L, CV of SG, TDDI: -8.8 U. No SAE, one hypoglycemic episode
Fabris et al[32], 2024, United States	Adults with T2D transitioned from PLGS to AID	Retrospective	796	NR	PLGS system (Basal-IQ Technology, Tandem Diabetes Care) (100)	AID (CIQ Technology, Tandem Diabetes Care)	3 months	Significant CFB in TIR (9%), TAR > 10 mmol/L (-8.9%), TAR > 13.9 mmol/L (-4.4%), mean SG: -0.65 mmol/L, TDDI: 6.5 U. No significant CFB in TBR < 3.9 mmol/L or < 3 mmol/L, CV of SG
Forlenza et al[33], 2022, United States1	At least 12 consecutive months of data available on CIQ, and had at least 30 days of ≥ 75% CGM data availability before and after CIQ initiation	Retrospective	500	NR, GMI 7.3% (6.9%-7.7%)	NR	Tandem t: Slim X2 CIQ system	3 months	Significant CFB in GMI (-0.2%), TIR (8%), TAR > 10 mmol/L (-5%), TAR > 13.9 mmol/L (-2%), mean SG: -0.47 mmol/L. No significant CFB in TBR < 3.9 mmol/L
Kadiyala et al[34], 2024, NCT04977908 and NCT04701424, United Kingdom1	Age ≥ 18 years, on subcutaneous insulin, HbA1c ≥ 11%	Retrospective	26	9 ± 1.4	Subcutaneous insulin (100)	CamAPS HX fully closed-loop system	8 weeks	At the end of the study after AID use: TIR (66.3%), TAR > 10 mmol/L (32.2%), TAR > 16.7 mmol/L (1.8%), TBR < 3.9 mmol/L (0.43%), TBR < 3 mmol/L (0.04%), mean SG: 9.17 mmol/L, SD of SG: 2.98 mmol/L, CV of glucose (322%)
Levy et al[35], 2024, NCT05111301, United States	either BBI therapy (MDI or via an insulin pump) or basal-only insulin for at least 3 months, TDDI ≤ 200 U, HbA1c 7.5%-12.0%	Prospective	30	8.6 ± 1.2	Basal insulin only (43), MDI (50), insulin pump (7)	T: Slim X2 insulin pump with CIQ technology	6 weeks	Significant CFB in TIR (15%), TAR > 10 mmol/L (-15%), TAR > 13.9 mmol/L (-2.7%), mean SG: -1.22 mmol/L. No significant CFB in TBR < 3.9 mmol/L or <3 mmol/L, CV of SG
Pasquel et al[36], 2025, NCT05815342 United States	Age 18-75 years, treated with a stable insulin regimen for at least 3 months prior to screening, HbA1c < 12%	Prospective	305	8.2 ± 1.3	MDI (73), basal insulin only (21), insulin pump (5.6), premix insulin injections (< 1)	Omnipod 5 AID System	13 weeks	Significant CFB in HbA1c (-0.8%), TIR (20%), TAR > 10 mmol/L (-20%), TAR > 13.9 mmol/L (-12%), TAR > 20 mmol/L (-5%), mean SG: -1.78 mmol/L, TBR < 3.9 mmol/L (0.0%), TBR < 3 mmol/L (0.01%) SD of SG: -0.61 mmol/L, coefficient of variation of SG (-0.7%). 13 patients experienced SAE and one severe hypoglycemia
Thijs et al[37], 2025, multiple countries in Europe	MM780G data uploaded to CareLink Personal from January 2020 to April 2024	Retrospective	26427	NR	NR	MiniMed 780G system	Mean observation period: Cohort A: 213 days, cohort B: 148 days	Cohort A: At the end of the study after AID use-TIR (71.1%), TAR > 10 mmol/L (27.9%), TAR > 13.9 mmol/L (6.6%), TBR < 3.9 mmol/L (1%), TBR < 3 mmol/L (0.2%), mean SG: 8.72 mmol/L, SD of SG: 2.82 mmol/L, GMI (7.1%). Cohort B: At the end of the study after AID use-TIR (75.1%), TAR > 10 mmol/L (24.3%), TAR > 13.9 mmol/L (4.9%), TBR < 3.9 mmol/L (0.6%), TBR < 3 mmol/L (0.1%), mean SG: 8.52 mmol/L, SD of SG: 2.48 mmol/L, GMI (7%). Both cohort A and cohort B had significant CFB in GMI (-0.5% and -0.3%, respectively), TIR (15.9% and 12.1%, respectively)

¹These studies included separate cohorts of type 1 diabetes and type 2 diabetes (T2D). We have considered only T2D cohort for this systematic review.

Data in mean ± SD or median (interquartile range). AID: Automated insulin delivery; BBI: Basal-bolus insulin; CFB: Change from baseline; CIQ: Control-IQ; CGM: Continuous glucose monitoring; CSII: Continuous subcutaneous insulin infusion; GMI: Glucose management indicator; HbA1c: Glycated hemoglobin; MDI: Multiple daily insulin injection; NR: Not reported; PLGS: Predictive low glucose suspend; SAE: Serious adverse event; SG: Sensor glucose; TAR: Time above range; TBR: Time below range; TDDI: Total daily dose of insulin; TIR: Time in range; T2D: Type 2 diabetes.

Table 3 Comparison of the efficacy outcomes in the automated insulin delivery vs the control arms at the end of the studies

Outcome variables (continuous)	Type of the randomized trial	Number of study reports	Number of participants with outcome analyzed		Pooled effect size, mean differences (95%CI)	P value	I2 (%)
			Automated insulin delivery arm	Control arm
TAR > 10 mmol/L (%)	All	5	294	186	-19.48 (-27.14 to -11.82)	< 0.00001	73
	Crossover	3	69	68	-20.69 (-33.35 to -8.03)	0.001	79
	Parallel-group	2	225	118	-18.38 (-31.42 to -5.35)	0.006	73
TAR > 13.9 mmol/L (%)	All	4	268	160	-8.33 (-12.89 to -3.77)	0.0003	71
	Crossover	2	43	42	-8.05 (-17.70 to 1.61)	0.10	79
	Parallel-group	2	225	118	-11.71 (-23.51 to 0.08)	0.05	73
TAR > 20 mmol/L (%)	Crossover	2	52	51	-4.39 (-6.79 to -1.98)	0.0004	0
TBR < 3.9 mmol/L (%)	All	5	294	186	-0.07 (-0.21 to 0.08)	0.37	22
	Crossover	3	69	68	-0.17 (-0.42 to 0.09)	0.20	32
	Parallel-group	2	225	118	0.00 (-0.09 to 0.09)	0.99	0
TBR < 3 mmol/L (%)	All	5	294	186	-0.01 (-0.03 to 0.02)	0.57	39
	Crossover	3	69	68	-0.03 (-0.09 to 0.03)	0.32	69
	Parallel-group	2	225	118	0.00 (-0.02 to 0.02)	1.00	0
Mean SG (mmol/L)	All	5	451	335	-1.21 (-1.93 to -0.49)	0.001	83
	Crossover	3	69	68	-1.82 (-3.34 to -0.30)	0.02	84
	Parallel-group	2	382	267	-0.66 (-1.34 to 0.03)	0.06	81
SD of SG (mmol/L)	Crossover	3	69	68	-0.40 (-0.64 to -0.15)	0.001	0
Coefficient of variation of glucose (%)	All	5	294	186	0.91 (-1.04 to 2.87)	0.36	68
	Crossover	3	69	68	0.51 (-2.90 to 3.93)	0.77	77
	Parallel-group	2	225	118	1.35 (-0.27 to 2.97)	0.10	17
Time using continuous glucose monitoring sensor (%)	Crossover	3	69	68	2.80 (1.55-4.05)	< 0.0001	13
TDDI (U)	All	6	458	344	-5.45 (-22.20 to 11.29)	0.52	74
	Crossover	3	69	68	13.24 (-11.64 to 38.12)	0.30	65
	Parallel-group	3	389	276	-21.07 (-30.15 to -11.99)	< 0.00001	0
TDDI (U/kg)	All	3	262	150	-0.04 (-0.20 to 0.11)	0.59	53
	Crossover	2	52	51	0.06 (-0.20 to 0.32)	0.67	50
	Parallel-group	1	210	99	-0.13 (-0.24 to -0.02)	0.02	Not reported

SG: Sensor glucose; TAR: Time above range; TBR: Time below range; TDDI: Total daily dose of insulin.

Table 4 Comparison of the safety outcomes in the automated insulin delivery vs the control arms

Outcome variables	Type of the randomized trial	Number of study reports	No. of participants with outcome/participants analyzed		Pooled effect size, risk ratio (95%CI)	P value	I2 (%)
			Automated insulin delivery arm	Control arm
Number of SAEs	All	4	24/234	15/229	1.58 (0.85-2.93)	0.15	0
	Crossover	2	6/52	3/51	1.92 (0.50-7.37)	0.34	0
	Parallel-group	2	18/182	12/178	1.50 (0.74-3.01)	0.26	0
Number of participants with SAEs	All	4	24/234	15/229	1.58 (0.85-2.93)	0.15	0
	Crossover	2	6/52	3/51	1.92 (0.50-7.37)	0.34	0
	Parallel-group	2	18/182	12/178	1.50 (0.74-3.01)	0.26	0
Number of SAEs (study-related)	All	3	6/208	3/203	1.85 (0.54-6.40)	0.33	0
	Crossover	1	1/26	0/25	2.89 (0.12-67.75)	0.51	N/A
	Parallel-group	2	5/182	3/178	1.71 (0.44-6.58)	0.44	0
Number of SAEs (not study-related)	All	5	41/449	20/333	1.37 (0.81-2.33)	0.24	0
	Crossover	2	6/52	4/51	1.47 (0.44-4.91)	0.53	0
	Parallel-group	3	35/397	16/282	1.44 (0.67-3.06)	0.35	29
Number of severe hypoglycemia events	All	4	2/281	0/170	2.10 (0.22-19.81)	0.52	0
	Crossover	2	1/52	0/51	3.00 (0.13-70.42)	0.50	N/A
	Parallel-group	2	1/229	0/119	1.46 (0.06-35.50)	0.82	N/A
Number of participants with severe hypoglycemic events	All	5	2/449	1/333	1.13 (0.18-7.10)	0.90	0
	Crossover	2	1/52	0/51	3.00 (0.13-70.42)	0.50	N/A
	Parallel-group	3	1/397	1/282	0.69 (0.07-6.57)	0.74	0
Number of non-SAEs	All	3	66/267	22/155	1.67 (1.07-2.63)	0.02	0
	Crossover	2	10/52	7/51	1.33 (0.54-3.28)	0.53	0
	Parallel-group	1	56/215	15/104	1.81 (1.07-3.04)	0.03	N/A
Number of participants with non-SAEs	All	4	154/435	120/318	1.08 (0.92-1.26)	0.35	0
	Crossover	2	9/52	7/51	1.22 (0.49-3.04)	0.67	0
	Parallel-group	2	145/383	113/267	1.07 (0.92-1.26)	0.38	0
Number of device deficiencies	All	4	53/281	3/170	9.13 (2.17-38.37)	0.003	0
	Crossover	2	11/52	1/51	6.90 (1.29-36.78)	0.02	0
	Parallel-group	2	42/229	2/119	19.93 (1.22-326.34)	0.04	N/A
Number of participants with device deficiencies	All	4	31/281	3/170	5.70 (2.11-15.36)	0.0006	0
	Crossover	2	10/52	1/51	6.49 (1.21-34.74)	0.03	0
	Parallel-group	2	21/229	2/119	5.31 (1.55-18.16)	0.008	0

N/A: Not applicable; SAEs: Severe adverse events.