Table 1.

Study characteristics and significant results, ordered by intervention and control devices.

Author(s) and study name	Number of adults and children (therapy)	Study design		Follow-up (months)	HbA1c (group difference)	Time in range/time in target mean (±SD)/ median (IQR) mean/median group difference (95% CI)	Time in hypoglycaemia mean (±SD)/median (IQR) mean/median group difference (95% CI)	Quality of life (group difference)
		Intervention (device)	Control (device)
Oskarsson et al.25 IMPACT Subgroup analysis	167 adults (MDI)	isCGM (FreeStyle Libre) (n = 75)	SMBG (n = 69)	6	No difference	70–180 mg/dl (3.9–10.0 mmol/l) Mean (baseline to follow-up) isCGM 15.0 (±2.6) to 15.7 (±2.8) h/day = 62.5 (±10.8) to 65.4 (±11.6)% SMBG 14.3 (±2.9) to 14.4 (±3.0) h/day = 59.6 (±12.1) to 59.6 (±12.5)% Difference in adjusted means 0.9 (0.2, 1.7) h/day** = 3.4 (0.08, 7.1)% Difference 6.5%	<70 mg/dl (3.9 mmol/l) Mean (baseline to follow-up) isCGM 3.44 (±2.10) to 1.86 (±1.36) h/day = 14.3 (±8.8) to 7.8 (±5.7)% SMBG 3.73 (±2.72) to 1.97 (±2.24) h/day = 15.5 (±11.3) to 15.3 (±11.6)% Difference in adjusted means −1.65 (−2.21, −1.09) h/day$$ = −6.9 (−9.2, −4.5)% Difference −46% <55 mg/dl (3.1 mmol/l) Mean (baseline to follow-up) isCGM 1.75 (±1.53) to 0.75 (±0.88) h/day = 7.3 (±6.4) to 3.1 (±3.7)% SMBG 1.99 (±1.97) to 1.97 (±2.24) h/day = 8.3 (±8.2) to 8.2 (±9.3)% Difference in adjusted means −1.10 (−1.55, −0.65) h/day$$ = −4.6 (−6.5, −2.7)% Difference −57.7%	↑ Satisfaction$$ ↓ Perceived frequency of hypoglycaemia** ↓ Perceived frequency of hyperglycaemia$$
Bolinder et al.32 IMPACT	241 adults (161 MDI; 78 CSII)	isCGM (FreeStyle Libre) (n = 119)	SMBG (n = 120)	6	No difference	70–180 mg/dl (3.9–10.0 mmol/l) Mean (baseline to follow-up) isCGM 15.0 (±2.5) to 15.8 (±2.9) h/day = 62.5 (±10.4) to 65.8 (±12.1)% SMBG 14.8 (±2.8) to 14.6 (±2.9) h/day = 65.8 (±11.7) to 60.8 (±12.1)% Difference in adjusted means 1.0 (±0.3) h/day3$$ = 4.2 (±1.3)%	<70 mg/dl (3.9 mmol/l) Mean (baseline to follow-up) isCGM 3.38 (±2.31) to 2.03 (±1.93) h/day = 14.1 (±9.6) to 8.5 (±8.0)% SMBG 3.44 (±2.62) to 3.27 (±2.58) h/day = 14.3 (±10.9) to 13.6 (±10.8)% Difference in adjusted means −1.24 (±0.239) h/day$$  = −5.2 (±1.0)% Difference −38.0% <55 mg/dl (3.1 mmol/l) Mean (baseline to follow-up) isCGM 1.59 (±1.42) to 0.80 (±0.96) h/day = 6.6 (±5.9) to 3.3 (±4.0)% SMBG 1.77 (±1.86) to 1.65 (±1.97) h/day = 7.4 (±7.8) to 6.9 (±8.3)% Difference in adjusted means −0.82 (±0.175) h/day$$ = −3.4 (±0.7)% Difference −50.3%	↑ Satisfaction$$ ↓ Perceived frequency of hyperglycaemia$$
Reddy et al.23 I HART extension	40 adults (MDI)	RT-CGM (Dexcom G5) (n = 16)	isCGM switching to RT-CGM (FreeStyle Libre) (n = 20)	2–4	No difference	70–180 mg/dl (3.9–10.0 mmol/l) Median (8 weeks to 16 weeks) RT-CGM 65.9–64.9% isCGM to RT-CGM 60.0–67.4% Median change RT-CGM −1.0 (−4.4 to 4.1)% isCGM to RT-CGM 3.5 (−0.4 to 7.2)%** 70–140 mg/dl (3.9–7.8 mmol/l) Median (8 weeks to 16 weeks) RT-CGM 43.7–43.1% isCGM to RT-CGM 40.4–42.9% Median change RT-CGM 1.0 (−2.6 to 3.2)% isCGM to RT-CGM 2.2 (−5.2 to 4.7)%	<70 mg/dl (3.9 mmol/l) Median (8 weeks to 16 weeks) RT-CGM 6.2–5.4% isCGM to RT-CGM 11.0–3.9%$$ Median change RT-CGM continued 0.4 (−0.2 to 2.1)% isCGM to RT-CGM −6.6 (−9.4 to −3.7)%$$ <54 mg/dl (3.0 mmol/l) Median (8 weeks to 16 weeks) RT-CGM 1.3–1.3% isCGM to RT-CGM 5.0–0.8%$$ Median change RT-CGM continued 0.02 (–1.2–0.5)% isCGM to RT-CGM −4.0 (−4.8 to −2.9)%$$ <50 mg/dl (2.8 mmol/l) Median (8 weeks to 16 weeks) RT-CGM 0.8–0.9% isCGM to RT-CGM 3.8–0.5%$$ Median change RT-CGM 0.0 (−0.9 to 0.3)% Is CGM to RT-CGM −3.1 (−4.6 to −2.4)%$$	↓ Hypo fear**
Reddy et al.26 I HART	40 adults (MDI)	RT-CGM (Dexcom G5) (n = 20)	isCGM (FreeStyle Libre) (n = 20)	2	No difference	70–180 mg/dl (3.9–10.0 mmol/l) Median (baseline to endpoint) RT-CGM 50.2–65.9% isCGM 54.1–60.0% Median change RT-CGM 12.7 (7.2–15.8)% isCGM 5.3 (1.1–11.7)%* Median between-group difference 7.4%* 70–140 mg/dl (3.9–7.8 mmol/l) Median (baseline to endpoint) RT-CGM 31.7–43.7% isCGM 34.8–40.4% Median change RT-CGM 10.6 (3.3–14.4)% isCGM 5.9 (−2.4 to 9.0)% Median between-group difference 4.7%	<70 mg/dl (3.9 mmol/l) Median (baseline to endpoint) RT-CGM 8.8–6.2% isCGM 11.9–11.0% Median change RT-CGM −2.7 (−6.1 to −0.1)% isCGM 0.6 (−2.1 to 5.4)%** Median between group difference −2.5% <50 mg/dl (2.8 mmol/l) Median (baseline to endpoint) RT-CGM 2.3–0.9% isCGM 4.1–3.8% Median change RT-CGM −1.2 (−4.3 to −0.5)% isCGM 1.3 (−1.0 to 2.4)%$ Median between group difference −4.3%	↓ Hypo fear**
Olafsdottir et al.6 GOLD-3	161 adults (MDI)	RT-CGM first (Dexcom G4) (n = 69)	SMBG first (n = 73)	16 (cross-over)	NI	NI	<70 mg/dl (3.9 mmol/l) Calculated mean (day + night) RT-CGM 2.8% = 0.7 h/day SMBG 4.8% = 1.1 h/day$$ <54 mg/dl (3.0 mmol/l) Calculated mean (day + night) RT-CGM 0.8% = 0.2 h/day SMBG 1.9% = 0.4 h/day$$	↑ Hypo confidence in social situations** and in avoiding problems$ and in avoiding hypo$ ↑ Free living$
Lind et al.30 GOLD	161 adults (MDI)	RT-CGM (Dexcom G4 Platinum) (n = 142)	SMBG (n = 142)	6 (cross-over)	Mean (baseline to follow-up) RT-CGM 8.6–7.92% = 70–63 mmol/mol SMBG 8.6 8.35% = 70–68 mmol/mol Mean of differences −0.43 (−0.57 to −0.29)%$$  =  −4.7 (−6.3 to −3.1) mmol/mol	NI	<70 mg/dl (3.9 mmol/l) Mean (baseline to follow-up) RT-CGM 5.52 (±4.33) to 2.79 (±2.97)% SMBG 5.12 (±4.24) to 4.79 (±4.03)% <54 mg/dl (3.0 mmol/l) Mean (baseline to follow-up) RT-CGM 2.31 (±2.39) to 0.79 (±1.23)% SMBG 2.06 (±2.42) to 1.89 (±2.12)%	↓ Hypo fear$$ ↑ Satisfaction$$
Heinemann et al.24 HypoDE	149 adults (MDI)	RT-CGM (Dexcom G5 Mobile) (n = 75)	SMBG (n = 74)	6	No difference	70–180 mg/dl (3.9–10.0 mmol/l) Median (baseline to follow-up) RT-CGM 57.8–58.5% = 13.9–14.0 h/day SMBG 59.1–56.5% = 14.2–13.6 h/day Adjusted between-group difference 3.1 (0.0–6.2)% = 0.75 (0.0–1.5) h/day*	<70 mg/dl (3.9 mmol/l) Median (baseline to follow-up) RT-CGM 5.0–1.6% = 1.2–0.4 h/day SMBG 6.9–6.4% = 1.7–1.5 h/day$$ <54 mg/dl (3.0 mmol/l) Median (baseline to follow-up) RT-CGM 1.7–0.3% = 0.4–0.1 h/day SMBG 2.7–2.5% = 0.65 to 0.6 h/day$$	↓ Hypo distress ↑ Satisfaction
Little et al.37 Hypo-COMPaSS 2-year follow-up	76 adults	RT-CGM (RT-CGM system, Medtronic) (n = 37)	SMBG (n = 39)	24	No difference	NI	No difference	No difference (± ↓ Hypo fear)
Little et al.35 Hypo-COMPaSS	96 adults (after randomization: 41 MDI; 42 CSII)	RT-CGM (RT-CGM system, Medtronic) (n = 42)	SMBG (n = 42)	6	No difference	NI	No difference	No difference
Polonsky et al.28 Further findings from DIAMOND	158 adults (MDI)	RT-CGM (Dexcom G4 Platinum) (n = 105)	SMBG (Bayer Contour Next USB; n = 53)	6	NI	NI	NI	↑ Hypo confidence** ↓ Diabetes distress** ↑ Satisfaction
Beck et al.31 DIAMOND	158 adults (MDI)	RT-CGM (Dexcom G4 Platinum) (n = 105)	SMBG (Bayer Contour Next USB) (n = 53)	6	Mean (baseline to follow-up) RT-CGM 8.6 (±0.7) to 7.7 (±0.8)% 70 (±7) to 61 (±9) mmol/mol SMBG 8.6 (±0.6) to 8.2 (±0.8)% 70 (±7) to 66 (±9) mmol/mol Mean change RT-CGM –1.0 (±0.8)% –11 (±9) mmol/mol SMBG 0.4 (±0.7)% –4 (±7) mmol/mol Between-group difference −0.6 (−0.8 to −0.3)%$$ −6 (−8 to −3) mmol/mol	70–180 mg/dl (3.9–10.0 mmol/l) Mean (baseline to follow-up) RT-CGM 11 (±3) to 12.3 (±3.4) h/day SMBG 10.8 (±2.8) to 10.8 (±3.2) h/day Mean adjusted difference 1.3 (0.1, 2.5) h/day** = 5.4 (0.4, 10.4)%	<70 mg/dl (3.9 mmol/l) Mean (baseline to follow-up) RT-CGM 1.1 (0.6–1.7) to 0.7 (0.5–1.2) h/day = 4.6 (2.5–7.1) to 2.9 (2.1–5.0)% SMBG 1.2 (0.6–2.3) to 1.3 (0.6–1.9) h/day** = 5.0 (2.5–9.6) to 5.4 (2.5–7.9)% <50 mg/dl (2.8 mmol/l) Mean (baseline to follow-up) RT-CGM 0.2 (0.1–0.5) to 0.1 (0.03–0.2) h/day = 0.8 (0.4–2.1) to 0.4 (0.1–0.8)% SMBG 0.3 (0.1–0.7) to 0.3 (0.1–0.7) h/day** = 1.3 (0.4–2.9) to 1.3 (0.4–2.9)%	NI
Van Beers et al.4 IN CONTROL	52 adults (29 MDI; 23 CSII)	RT-CGM (Enlite glucose sensor; Medtronic) (n = 26)	SMBG (n = 26)	2 × 4 (cross-over)	No difference	72–180 mg/dl (4.0–10.0 mmol/l) Mean (CI) RT-CGM 65.0 (62.8–67.3)%  = 15.6 (15.1–16.2) h/day SMBG 55.4 (53.1–57.7)%  = 13.3 (12.7–13.8)$$ Mean difference (CI) 9.6 (8.0–11.2)% = 2.3 (1.9–2.7) h/day$$	<70 mg/dl (3.9 mmol/l) Mean (CI) RT-CGM 6.8 (5.2–8.3)%  = 1.6 (1.3–2.0) h/day SMBG 11.4 (9.9–13.0)% = 2.7 (2.4–3.1) h/day$$ Mean difference (CI) −4.7 (−5.9 to −3.4)% = −1.1 (−1.4 to −0.8) h/day$$	No difference
Hommel et al.34 SWITCH	81 adults and 72 children (CSII)	RT-CGM (MiniMed SofSensor; Medtronic) (n = 77)	SMBG (n = 76)	2 × 6 (cross-over)	NI	NI	NI	No difference in children’s self-rating ↑ Parents’ proxy rating$ ↑ Satisfaction** ↑ Convenience** ↑ Flexibility**
Tumminia et al.36	20 adults (10 MDI; 10 CSII)	RT-CGM first (Guardian REAL-Time Clinical; Medtronic) (n = 20)	SMBG first (n = 20)	2 × 6 (cross-over)	Baseline to follow-up MDI with RT-CGM 8.58 (±0.2) to 7.71 (±0.2)%** 70 (±3) to 61 (±3) mmol/mol** Calculated change −0. 87% (−9 mmol/mol) SAP 8.50 (±0.3) to 7.82 (±0.2)%** Calculated change −0.68% (−7 mmol/mol)	NI	<70 mg/dl (3.9 mmol/l) Baseline to follow-up MDI + RT-CGM AUC 1.5 (±2.4) to 0.5 (±0.5)** MDI + SMBG AUC 1.5 (±0.5) to 1.8 (±1.0) SAP AUC from 1.7 (±0.3) to 1.5 (±0.3) CSII + SMBG AUC from 1.7 (±1.0) to 3 (±1.3)	NI
Burckhardt et al.21	49 Children & their Parents (20 MDI; 29 CSII)	RT-CGM (Dexcom G5 Mobile) (n = 48)	SMBG (n = 48)	2 × 3 (cross-over)	No difference	NI	NI	↓ Hypo fear$$ ↓ Family impact$ ↓ Stress$ ↑ Improvement of psychosocial metrics$ ↑ Satisfaction**
Abraham et al.27	154 Children (CSII)	HCL with PLGS (MiniMed 640G pump with Suspend before low, Medtronic; Enlite Sensor and Guardian 2 Link transmitter, Medtronic) (n = 80)	SAP (same devices but without suspend on low and suspend before low) (n = 74)	6	No difference	NI	<54 mg/dl (3.0 mmol/l) Mean (baseline to follow-up) PLGS 1.3–0.6%$$ SAP 1.4–1.2%** Difference in LS means −0.44 (−0.64 to −0.24)%$$	No difference
Tauschmann et al.22	44 adults and 42 children (CSII)	HCL with PLGS (640G, Medtronic; Enlite 3 glucose sensor, Medtronic; Contour Next Link 2.4 glucometer, Ascensia Diabetes Care) (n = 46)	SAP (same devices but without suspend on low and suspend before low; n = 40)	3	Mean (baseline to follow-up) HCL 8.0–7.4% = 63–57 mmol/mol SAP 7.8–7.7% = 62–60 mmol/mol Difference (CI) −0.36 (−0.53 to −0.19)%$$ = −4 (−5.8 to −2.2) mmol/mol	70–180 mg/dl (3.9–10.0 mmol/l) Mean (baseline to follow-up) HCL 52 (±10) to 65 (±8)% SAP 52 (±9) to 54 (±9)% Difference (CI) 10.8 (8.2–13.5)%$$	<70 mg/dl (3.9 mmol/l) Median (baseline to follow-up) HCL 3.5 (2.0–5.4) to 2.6 (1.9–3.6)% SAP 3.3 (1.2–5.5) to 3.9 (1.7–5.3)% Difference (CI) −0.83 (−1.40 to −0.16)%** <50 mg/dl (2.8 mmol/l) Median (baseline to follow-up) HCL 0.4 (0.1–1.0) to 0.3 (0.2–0.6)% SAP 0.5 (0.1–1.0) to 0.5 (0.2–0.9)% Difference (CI) −0.09 (−0.24 to 0.01)% (p = 0.11)	No difference
Barnard et al.29	32 adults and 26 children (CSII)	HCL with PLGS (Dana R pump, Diabecare; FreeStyle Navigator II, Abbott Diabetes Care) (n = 38)	SAP (same devices but without Suspend on low and Suspend before low) (n = 30)	2 × 3 (cross-over)	NI	NI	NI	No difference (both groups ↑ satisfaction)
Thabit et al.33	33 adults (CSII)	HCL with PLGS (Florence D2A or similar automated closed-loop glucose control system; FreeStyle Navigator II CGM System, Abbott Diabetes Care) (n = 32)	SAP (CSII Dana R Diabecare; real-time FreeStyle Navi-gator CGM) (n = 33)	2 × 3 (cross-over)	Baseline to follow-up HCL 7.6–7.3% = 60– 56 mmol/mol SAP 7.6–7.6% 60–60 mmol/mol Paired difference (CI) −0.3 (−0.5 to −0.1)%$ = −4 (−6 to −2) mmol/mol	70–180 mg/dl (3.9–10.0 mmol/l) Mean (at follow-up) HCL 67.7 (±10.6)% SAP 56.8 (±14.2)% Paired difference (CI) 11.0 (8.1–13.8)%$$	<70 mg/dl (3.9 mmol/l) Median (at follow-up) HCL 2.9 (1.4–4.5)% SAP 3.0 (1.8–6.1)% Paired difference (CI) −0.81 (0.68–0.96)%** <50 mg/dl (2.8 mmol/l) Median (at follow-up) HCL 0.3 (0.1–0.7)% SAP 0.4 (0.1–0.9)% Paired difference (CI) −0.45 (0.31–0.65)%$$	NI

To compare RCTs, time in range, time in target and time in hypoglycaemia were calculated to %/day if they reported hours or minutes/day.

^*p = 0.05.

^**p < 0.05.

^$p < 0.005.

^$$p < 0.001.

AUC, area under curve; CI, confidence interval; CSII, continuous subcutaneous insulin infusion; isCGM, intermittently scanned (flash) continuous glucose monitoring; HCL, hybrid closed-loop system; IQR, interquartile range; MDI, multiple daily injection; NI, not investigated; PLGS, predictive low-glucose suspend; SAP, sensor-augmented pump therapy; SD, standard deviation; SMBG, self-monitoring of blood glucose; RT-CGM, real-time continuous glucose monitoring.