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. 2020 Jul 7;11(6):1388–1402. doi: 10.1111/jdi.13290

Table 2.

Clinical trials evaluating continuous glucose monitoring use in type 1 diabetes patients with impaired awareness of hypoglycemia

Authors (year) Main objective Trial design and targeted population Primary outcome(s) Baseline population characteristics CGM models (active usage time)
Ly et al. (2011) 130 Assess if the use of CGMs with preset hypo alarms (at glucose 108 mg/dL) improves counterregulatory response to hypoglycemia.

Randomized, controlled.

Two arms (CGM vs SMBG).

Duration: 4 weeks.

Adolescents (aged 12–18 years) with IAH defined per modified Clarke (n = 11).

 Epinephrine response to hypoglycemia measured during hypoglycemia clamp study.

CGM n = 6; SMBG n = 5

Female: Not reported

Age:

  • CGM:13.7 ± 0.7 years

  • Standard: 15 ± 0.8 years

DoD:

  • CGM: 5.2 ± 1.4 years

  • Standard: 6.5 ± 1.2 years

HbA1c:

  • CGM: 7.7 ± 0.2%

  • Standard: 7.9 ± 0.3%

MDI: Not reported

 Medtronic Minimed paradigm real‐time system (not reported)
Little et al. (HypoCOMPaSS; 2014) 131 ; Leelarathna et al. (HypoCOMPaSS clamp sub‐cohort study; 2013) 132 Determine if rigorous hypoglycemia prevention improves hypoglycemia awareness and prevents SH development in patients with IAH, independent of insulin delivery and glucose monitoring modalities.

Randomized, controlled.

2 × 2 factorial (CGM vs SMBG, CSII vs MDI).

Duration: 24 weeks.

Patients with IAH defined per Gold. (n = 96)

Difference in hypoglycemia awareness (assessed with Gold) between the CGM and SMBG groups, and between the MDI and CSII groups.

Clamp subcohort study: the glucose concentration at which participants felt hypoglycemic during progressive hypoglycemia.

83 patients completed study; CGM n = 42 and SMBG n = 41

Female: 64%

Age: 48.6 ± 12.2 years

DoD: 28.9 ± 12.3 years

HbA1c: 8.2 ± 1.2%

MDI: 97%

Clamp Subcohort

n = 18 (CGM n = 11, SMBG n = 7)

Female: 66.7%

Age: 50 ± 9 years

DoD: 35 ± 10 years

HbA1c: 8.1 ± 1%

MDI: 50%

 Medtronic (median 57%)
van Beers et al. (IN CONTROL; 2016) 133 Assess whether CGM use improves glycemia control and prevents severe hypoglycemia in patients with IAH.

Randomized, cross‐over.

Two arms (CGM vs SMBG).

Duration: 16‐week intervention with 12‐week washout.

Patients with IAH defined per Gold, either on CSII or MDI. (n = 52)

 Mean difference in the percentages of time in normoglycemia.

CGM n = 26, SMBG n = 26

Female: 46%

Age: 48.6 ± 11.6 years

DoD: 30.5 ± 40.8 years

HbA1c: 7.5 ± 0.8%

MDI: 56%

 Medtronic Enlite glucose sensor (median 89.4; IQR 80.8–95.5);
Rickels et al. (2018) 134 Assess if hypoglycemia avoidance with CGMs improves glucose counterregulation in patients with long‐standing diabetes and IAH.

Single arm (CGM).

Duration: 18 months.

Patients with IAH defined per Clarke and other criteria † . (n = 11)

 Difference in the endogenous glucose production response during stepped‐hypoglycemic and euglycemic clamps.

Female: 55%

Age: 44 ± 4 years

DoD: 31 ± 4 years

HbA1c: 7.2 ± 0.2%

MDI: 27%

Dexcom seven plus/G4 or Medtronic Sof‐Sensor (n = 7/4)

(median 100%)
Heinemann et al. (HypoDE; 2018) 135 Ascertain whether the incidence and severity of hypoglycemia can be reduced through CGM use in patients on MDI and with high risk for developing SH.

Randomized, controlled.

Two arms (CGM vs SMBG).

Duration: 22‐week intervention and 4‐week follow up.

Patients on MDI with SH within the last year or IAH defined per Clarke. (n = 149)

 The mean difference in the number of hypoglycemic events (defined as CGM glucose ≤54 mg/dL for ≥20 min) between baseline and the follow up phase.

141 patients in final analysis; CGM n = 75, SMBG n = 66

Female:

  • CGM: 47%

  • Control: 34%

Age:

  • CGM: 45.8 ± 12.0 years

  • Control: 47.3 ± 11.7 years

DoD:

  • CGM: 21.6 ± 13.9 years

  • Control: 20.9 ± 14.0 years

HbA1c:

  • CGM: 7.6 ± 1.0%

  • Control: 7.3 ± 1.0%

MDI: 100%

 Dexcom G5 (mean 90.7%)
Reddy et al. (I‐HART; 2018) 141 Assess the impacts of CGMs and FGMs on hypoglycemia reduction in patients on MDI with high risk for developing SH.

Randomized.

Two arms (CGM vs FGM).

Duration: 8 weeks.

Patients on MDI with SH within the last year or IAH defined per Gold (n = 40)

 The median difference between the change of time in hypoglycemia (<59 mg/dL) from baseline to end‐point.

CGM n = 20, SMBG n = 20

Female: 40%

Age: 49.5 years (37.5–63.5)

DoD: 30.0 years (21.0–36.5)

HbA1c: 7.3% (6.5–7.8)

MDI: Not reported ‡

Dexcom G5 (not reported)

Data presented in mean ± standard deviation or median (interquartile range [IQR]).

AUC, area under the curve; CSII, continuous subcutaneous insulin infusion; DoD, duration of diabetes; HbA1c, hemoglobin A1C; IAH, impaired awareness of hypoglycemia; SH, severe hypoglycemia; SMBG, self‐monitoring of blood glucose; T1D, type 1 diabetes.

†

Severely problematic hypoglycemia (hypoglycemia [hypo] score ≥1,047), marked glycemic lability (glycemic lability index ≥433 mmol/L2/h/week or a composite of HYPO score ≥423 and glycemic liability index ≥329 mmol/L2/h/week, and either at least one episode of severe hypoglycemia in the past 12 months or the presence of >5% of time spent at <60 mg/dL by 72‐h blinded continuous glucose monitoring (CGM).

‡

The study aimed to assess the CGM effects on multiple daily injection (MDI)‐using population; actual percentage not reported.