Table 4.
Overview of Randomized, Controlled Studies on the Use of Continuous Glucose Monitoring Systems to Accompany Therapy
| Study/first author | RCT? (country) | System or systems manufacturer(s) | Inclusion criteria | N | Baseline HbA1c, blood glucose | Duration (weeks) | Result | Comment | Industry sponsored? | |
| Algorithm-derived (special sensor training); data algorithm explained at http://direcnet.jaeb.org and by Buckingham and coauthors48 | JDRF24 | Yes (U.S.) | Dexcom, Abbott, Medtronic | >8 years old; duration of diabetes > 1 year; type 1 diabetes; HbA1c 7–10%; at least three blood glucose self-tests daily; one week of sensor prior knowledge | 322 | >25 years: 7.6 (experimental), 7.6 (control); 15–24 years: 8.0 (experimental), 7.9 (control); <15 years: 8.0 (experimental), 7.9 (control) | 26 | 7.1 (experimental), 7.6 (control), p < .001; 7.8 (experimental), 7.7 (control), p < .52; 7.6 (experimental), 7.7 (control), p < .29 |
Real-time CGM has the ability, in adults who are motivated and who integrate it into their everyday lives, to reduce the HbA1c; this primary end point was achieved in adults but not in children and young people; the cause was the wearing time of less than 70%, which can be assumed from a per-protocol analysis | No |
| JDRF14 | Yes (U.S.) | Dexcom, Abbott, Medtronic | >8 years old; duration of diabetes > 1 year; type 1 diabetes; HbA1c <7%; at least three blood glucose self-tests daily; one week of sensor prior knowledge | 129 | 6.4 (experimental),6.5 (control) | 26 | 6.4 (experimental),6.8 (control); time < 70 mg/dl/day (median): 91 min → 54 min, p = .02 (experimental); 96 min → 91 min, not significant (control)10 versus 11 patients with severe hypoglycemia |
A reduction in HbA1c was not intended and not a primary end point; the primary end point was time of <70 mg/dl; well-controlled, motivated diabetes patients, including children, use the real-time CGM frequently and sustainably; reduction in time |
No | |
| MITRE Study49 | Yes (U.K.);CGM group, control group, and attention control group | CGMS (without RT),Glucowatch (RT) | Adults, HbA1c 2 × >7.5%; type 1 and type 2 diabetes 50/50 | 404 | 9.2 % Glucowatch,9.0 % CGMS,8.9 % attention,9.4% control | 79 | 9.1% Glucowatch,8.55% CGMS,8.3 % attention,8.8 % control | Glucowatch results in harmony with earlier DirecNet study; wearing behavior of Glucowatch markedly restricted due to side effects;JDRF and Mitre not in harmony in adults, which may be due to the JDRF’s real-time CGM | No | |
| DirecNet50 | No (U.S.); no control group without sensor; IIT | Abbott | 3–18 years old; type 1 diabetes; DATA algorithm | 45 | 7.1 (CSII), 7.8 (IIT) |
26 | 7.0 (CSII + CGM), p = .53, n= 24; 7.6 (CSII + CGM), p = .26, n= 21 |
Wearing time fell over time; sensor was worn, on average, for half of the weekly hours; baseline characteristics revealed no predictors for successful wearing | Yes | |
| Algorithm-derived (special sensor training); data algorithm explained at http://direcnet.jaeb.org and by Buckingham and coauthors48 | Bailey51 | No (U.S.) | Dexcom | IIT or CSII; >18 years old; no pregnancy; type 1 and type 2 diabetes | 140 | 7.6 | 12 | 7.2; p < .001 | Unfortunately, there was no control group, type 2 diabetes patients and those with poor baselines without insulin pump also benefited | Yes |
| SaP | STAR123 | Yes (U.S.) | Medtronic | 12–72 years old | 146 | 8.49 (experimental), 8.39 (control) |
26 | 7.77 (experimental), 7.84 (control),experimental versus control; not significant, p = .37; 11 severe hypoglycemia with real-time CGM;3 severe hypoglycemia in control |
The primary end point was not reached; the authors conclude: “The results are strongly suggestive of the fact that the right patient selection should include the willingness and ability to use the technology correctly”; they felt this was an important “screening tool” for recognizing potential candidates | Yes |
| STAR329 | Yes (U.S.) | Medtronic | 7–70 years old; HbA1c 7.4–9.5%; previously IIT | 485 | 8.3 (experimental; SaP), 8.3 (control; IIT) |
XXXX | 7.5 (experimental; SaP; experimental vs. control: p < .001),8.1 (control; IIT), 7.9 (experimental, SaP; children; experimental versus control; p < .001), 8.5 (control, children); severe hypoglycemia in both groups identical (5 per 100 patient years) |
In the IIT group (control group), the sensor gathers data; the current glucose values are not displayed; in this study, it is not possible to determine the influence of the insulin pump per se or the additional influence of the sensor-augmented algorithm separately | Yes | |
| ONSET52 | Yes (Europe); multicenter | Medtronic | 1–16 years old; new manifestation of type 1 diabetes in the past four weeks | 160 | 11.2 (experimental; SaP), 11.5 (control; CSII) |
52 | 7.4 (experimental; SaP), 7.6 (control; CSII), experimental versus control not significant |
The SaP (experimental) is compared with conventional blood glucose self-monitoring (control), even with C-peptide and depression scale in patients following the new manifestation of type 1 diabetes; no significant differences | Yes | |
| SaP | REAL-TREND27 | Yes (France) | Medtronic | HbA1c > 8% below IIT; duration of diabetes > 12 months; in SaP group: agreed to wear CGM for >70% of the time; versus CSII (control) | 132 (51 children, 81 adults) | 9.11 (experimental; SaP), 9.28 (control; CSII) |
26 | 8.3 (experimental; SaP), p < .001; 8.7 (control; CSII), p < .001; experimental versus control, p = .006 (all patients);experimental versus control, p = .004 (patients per protocol); severe hypoglycemia not significant |
The aim was an intention-to-treat analysis; however, a per-protocol population was formed that did not contain 23 patients who had measured less than 70% of the time; in this case, the HbA1c difference achieved significance; 14 from the sensor group (SaP) and 6 from the CSII group left the study | Yes |
| EURYTH-MICS28 | Yes (Europe); multicenter | Medtronic | 18–65 years old; HbA1c > 8.2%in patients on IIT | 87 | 8.46 (experimental), 8.59 (control) |
26 | 7.23 (experimental; SaP), p < .001; 8.46 (control; IIT), not significant;experimental versus control, p < .001; no significant difference in severehypoglycemia |
Control group, IIT; the result is a summation effect of the insulin pump, sensor, and BolusExpert and cannot be ascribed solely to the sensor | Yes | |
| SWITCH31 | Yes (Europe); cross-over; multicenter | Medtronic | 6–70 years old; CSII > 6 months; HbA1c 7.5–9.5% | 124 | Not yet published | 26 | Study participants first had to complete three tests and were required to use the device at least 80% of the time | Yes | ||
| Battelino30 | Yes (Europe) | Abbott | 10–65 years old; IIT or CSII; HbA1c < 7.5% | 120 | 6.92 (experimental), 6.91 (control) |
26 | 6.69 (experimental), p < .05; 6.95 (control), not significant; experimental versus control, p = .008; time in hypoglycemia 0.48 h/day (experimental), 0.97 h/day (control), p = .03; no severe hypoglycemia in either group |
Patients were given instructions on how to use the sensor, but no algorithms; the primary outcome was the time spent below 63 mg/dl | Yes | |
| Therapy left up to the patient (no special training, no computer), “patient-led use” |
ASAP Study26 | Yes (Australia) | Medtronic | Type 1 diabetes; 13–40 years old; HbA1c < 8.5%; motivated, relatively well-adjusted insulin pump patients with prior knowledge of bolus calculation | 62 | 7.3 (experimental), 7.5 (control) |
13 | 7.1 (experimental), 7.8 (control), difference adjusted -0.43, p = .009; difference -0.51 with sensor use > 70%; no severe hypoglycemia in either group |
Motivational tool, “The relatively high rate of patients who left the study and who did not follow the protocol showed that this technology is not universally acceptable and is for some too much of a burden.” | Yes |
| Danne53 | No (Europe); concealed and unconcealed phase |
Abbott | Type 1 diabetes; >18 years old; duration of diabetes > 1 year; primary end point blood glucose outside 3.9–10 mmol/liter | 48, of which 39 were CSII | Hours outside 3.9–10 mmol/liter: 11 ± 4.5 | 60 | 9.5 ± 4.0, p = .002 | An age-independent effect was found to occur on glycemic variability; all apart from one patient wore the device for >85% of the time | Yes | |
| Garg54 | Yes (U.S.) | Dexcom | Type 1 diabetes, type 2 diabetes, with insulin; comparison of concealed versus unconcealed CGM | 91 (75 type 1 diabetes, 16 type 2 diabetes) | Time frame/day <55 mg/dl: 0.94 h, >240 mg/dl: 6.46 h | 3 x 72 h | Secondary end point: time/day (h/day), <55 mg/dl, 0.94 (concealed) → 0.74 (unconcealed) -21%, p < .0001; >240 mg/dl, 6.46 (concealed) → 4.99 (unconcealed) -23%, p < .0001 |
The study was too short for an HbA1c comparison; primary end points were errors and accuracy; the secondary end point showed that the timeframe in the near-normoglycemic range rose; pilot study for Dexcom | Partially | |
| Guard Control22 | Yes (Europe) | Medtronic | Three study arms: permanent real-time CGM, every two weeks for three days, and monitoring only IIT or CSII | 162 (81 children, 81 adults) | 9.5 (experi-mental 1), 9.6 (experi-mental 2), 9.7 (control) |
13 | 8.5 (experimental 1 versus control, p = .003); 8.9 (experimental 2 versus control, not significant); 9.3 (control) |
First study with real-time CGM and measurement of HbA1c values; the high baseline value of the HbA1c should be noted; permanent use (experimental 1) with more effective improvement than intermittent use (experimental 2) | Yes |