Table 1.

Studies of CGM use in T2D, 2016–2021

Author/year	Aim(s)	Sample	Main outcomes	Results
Randomized controlled trials
Beck, 2017 [4•]	Determine effectiveness of rtCGM vs. usual care (SMBG at least 4 times a day) Intervention group received general guidelines about using CGM and their clinicians individualized recommendations about incorporating CGM trend information into their diabetes management	253 participants Age ≥ 25 (mean age 60) Median diabetes duration = 17 years T2D treated with MDI for ≥ 1 year Baseline A1c 7.5–10.0 (mean = 8.5) Stable diabetes medications and weight over prior 3 months	Clinical: Change in A1c, baseline to 24 weeks Other A1c and CGM outcomes, weight Psychosocial: General QoL, hypoglycemia unawareness, fear of hypoglycemia, diabetes distress, hypoglycemia confidence	Clinical: CGM use sustained at 6.7 days/week in month 6 Adjusted difference in mean change in A1c =  − 0.3% (p = .005) at 12 weeks and − 0.3% (p = .002) at 24 weeks Median CGM TIR increased from 802 to 882 min/day in CGM group and 794 to 836 min/day in control group, reflecting a greater reduction in time above range in the CGM group and a reduction in time below range in the CGM group with no change in time below range in control group Weight: CGM group experienced a 1.3 kg weight gain and a 0.2 kg weight loss in control group Psychosocial: No difference in QoL, fear of hypoglycemia, diabetes distress, hypoglycemia confidence, or hypoglycemia unawareness
Haak, 2017 [5•]	Assess safety and efficacy of isCGM to replace SMBG	224 participants with type 2 diabetes on intensive insulin therapy randomized 2:1 to isCGM or SMBG Intervention participants entered additional 6-month follow-on phase after initial 6-month RCT	Primary: change in A1c from baseline to 6 months Secondary: time in hypoglycemia, effect of age, patient satisfaction, at 6 months At 12 months: time in range, time in hypoglycemia, nocturnal hypoglycemia, frequency of SMBG checks	Change in A1c: No difference in full sample between CGM (− 0.29%) and SMBG (− 0.31%), p = 0.82 Significant difference for participants age < 65 years between CGM (− 0.53) and SMBG (− 0.20), p = .03 Time in hypoglycemia: Time below 70 mg/dL: reduced for CGM compared to SMBG (reduced 43% from baseline or − 0.47 h/day, p = .0006) Time below 55 mg/dL: reduced for CGM compared to SMBG (reduced 53% from baseline or − 0.22 h/day, p = .0014) Treatment satisfaction was higher for CGM than for SMBG (p < .0001) In the 6-month follow-on, at 12 months, there was no change in TIR; time below 70 mg/dL was reduced by 50% or − 0.70 h/day over baseline, p = .0002; nocturnal hypoglycemia was reduced by 52%, p = .0002; SMBG decreased from 3.9 to 0.2 checks per day
Ruedy, 2017 [6]	Determine the effectiveness of rtCGM in adults ≥ 60 years old with T1D or T2D using insulin via MDI	116 participants ≥ 60 years old (mean 67 years) with T1D (34) or T2D (82) using MDI therapy for at least 1 year and with baseline HbA1c 7.5–10.0% randomized to rtCGM or SMBG (4 + checks/day) for 24 weeks. Baseline HbA1c 8.5	Primary: change in HbA1c at 24 weeks Secondary: time < 60 mg/dL, time > 250 mg/dL, time 70–180 mg/dL, CV at 12 and 24 weeks	HbA1c decreased more in CGM group (− 0.9%) than in SMBG group (− 0.5%) at 24 weeks; adjusted difference in mean change in HbA1c − 0.4%, p < .001 There were significantly greater improvements in mean glucose, time in range, and time in hyperglycemia in the CGM group compared to the SMBG group at 24 weeks No differences were seen between groups in time in hypoglycemia, but there was very little time in hypoglycemia at baseline, limiting ability to detect a significant difference
Wada, 2020 [7•]	Evaluate isCGM compared to SMBG in patients with T2D not treated with insulin	100 adults with T2D not treated with insulin and not using CGM or SMBG randomized to receive isCGM or SMBG Devices (CGM or SMBG) were available to participants for 12 weeks	Primary: change in HbA1c at 12 and 24 weeks Secondary: changes in other clinical measures (e.g., BMI, BP, FPG, HDL, CGM metrics including time < 70 mg/dL, time < 55 mg/dL, TIR, time > 180 mg/dL, time > 240 mg/dL, time > 300 mg/dL, mean glucose, glucose variability (SD, CV, MAGE, BGRI, CONGA, MODD) Non-biologic: change in treatment satisfaction	A1c reduced from baseline to 12 weeks for CGM (− 0.43, p < .001) and for SMBG (− 0.30, p = .001), with the between-group difference of − 0.13% not significant, p = .241; the reduction was sustained for the CGM group at 24 weeks (− 0.46, p < .001) but not for SMBG (− 0.17, p = .124), for a significant between-group difference of − 0.29, p = .022 Significant differences were seen between CGM and SMBG for decreases in mean glucose (− 15 mg/dL, p < .001), SD (− 5, p < .001), time > 180 mg/dL (− 2.66 h/day), time > 240 mg/dL (− 1.23 h/day), and time > 300 mg/dL (− 0.39 h/day), all p < .001 Significant difference between CGM and SMBG for increase in time in range (2.36 h/day, p < .001) Time below range and CV did not change significantly Treatment satisfaction increased significantly for CGM compared to SMBG, with a difference increase of 3.4, p < .001
Martens, 2021 [8]	Determine effectiveness of CGM in adults with T2D treated with basal insulin in primary care practices	175 adults with T2D on basal-only insulin therapy, receiving diabetes care from a primary care physician, randomized 2:1 to CGM (n = 116) or SMBG (n = 59)	Primary: HbA1c at 8 months Secondary: CGM-measured TIR, time > 250 mg/dL, mean glucose level at 8 months	Mean HbA1c decreased from 9.1 to 8.0% at 8 months in the CGM group, compared to 9.0% to 8.4% in the SMBG group (adjusted difference − 0.4%, p = .02) TIR was 59% in the CGM group compared to 43% in the SMBG group (adjusted difference 15%, p < .001) Time > 250 mg/dL was 11% in the CGM group compared to 27% in the SMBG group (adjusted difference − 16%, p < .001) Mean glucose was 179 mg/dL in the CGM group compared to 206 mg/dL in the SMBG group (adjusted difference − 26 mg/dL, p < .001)
Yaron, 2019 [9]	Assess treatment satisfaction and effectiveness of isCGM in T2D patients using basal-bolus insulin	101 participants with T2D on MDI insulin therapy randomized to isCGM or SMBG (4 + checks/day) for 10 weeks	Primary: treatment satisfaction Secondary: change in HbA1c, change in quality of life, percentage of participants reaching physician recommended personal A1c target, changes in hypoglycemia events (< 70 mg/dL and < 54 mg/dL)	Treatment satisfaction was high in both groups, with the observed difference not significant (p = .053) for mean DTSQ score, and likewise for most DTSQ individual items. However, flexibility was rated as higher for CGM than for SMBG (2.28 vs. 1.61, p = .019), and CGM participants were more willing to recommend CGM than SMBG participants were to recommend SMBG (2.61 vs. 2.19, p = .023) HbA1c reduced from baseline to 10 weeks more for CGM (-0.82%) than for SMBG (− 0.33%); unadjusted mean change − 0.49%, p = .005, mean change adjusted for baseline HbA1c − 0.53%, p < .001 69% of CGM group vs. 30% of SMBG group experienced HbA1c decrease of ≥ 0.5% 39% of CGM group vs. 19% of SMBG group experienced HbA1c decrease of ≥ 1.0% No difference seen in hypoglycemia, but CGM group hypoglycemia was based on CGM readings and self-report, while SMBG group hypoglycemia was based on SMBG readings and self-report
Davis, 2020 [10]	Assess efficacy of isCGM compared with SMBG in reducing incidence of hypoglycemia among insulin-treated adults with a recently confirmed episode of clinically significant hypoglycemia	59 adult participants with T2D (17), T1D (40), or LADA (2) treated with insulin and with event of symptomatic hypoglycemia with glucose < 72 mg/dL or of glucose < 54 mg/dL within 2 weeks prior to recruitment, randomized to isCGM or SMBG for 6 months	Primary: hypoglycemia requiring second-party assistance Secondary: self-reported hypoglycemia, blood/interstitial glucose < 54 mg/dL, blood/interstitial glucose 54–70 mg/dL, blood/interstitial glucose < 72 mg/dL, change in HbA1c	No difference in severe hypoglycemia between CGM and SMBG groups Higher incidence in CGM than SMBG of any self-reported hypoglycemia (114 vs. 78 events/person-year, p < .001), blood/interstitial glucose < 54 mg/dL (67 vs. 33 events/person-year, p < .001), blood/interstitial glucose 54–70 mg/dL (137 vs. 64 events/person-year, p < .001), blood/interstitial glucose < 72 mg/dL (205 vs. 96 events/person-year, p < .001) No difference in change in HbA1c between CGM and SMBG groups (− 0.21 vs. − 0.06, p = .40)
Cox, 2020 [11]	Compare conventional medication management of T2D to medication management plus GEM lifestyle intervention plus rtCGM	RCT of 30 adults with T2D not treated with insulin, with HbA1c > 7.0	Primary: change in HbA1c from baseline to 6 months WHO QoL, diabetes empowerment, DDS, glucose monitoring satisfaction survey	Intervention participants experienced a greater decrease in HbA1c than controls (mean difference –1.2%, p = .03), which decreased from 8.9 to 7.6% and 8.8 to 8.7%, respectively Intervention participants experienced significant benefits compared to controls on secondary outcome measures including WHO QoL (psychological subscale), diabetes empowerment, diabetes distress (emotional and regimen subscales), and glucose monitoring satisfaction
Meta-analyses evaluating change in glycemia
Park, 2018 [12]	Synthesize evidence of effectiveness of CGM in adults with T2D	7 RCTs and 3 cohort studies: 8 studies involving 1384 participants for rtCGM and proCGM, and 2 studies involving 4902 subjects for isCGM	Difference in HbA1c change between CGM and controls	rtCGM and proCGM were associated with a greater reduction in HbA1c compared to controls; standard mean difference − 0.20 (95% CI − 0.09 to − 0.31) among all 8 rtCGM/proCGM studies (7 RCTs and 1 cohort study), and − 0.33 (95% CI − 0.13 to − 0.52) among the 7 RCTs Pooled analysis of 2 studies of isCGM (1 RCT, 1 case control) showed no difference between the CGM and control; standard mean difference [− 0.02% (95% CI − 0.07 to 0.04)]
Ida, 2019 [13]	Investigate the effects of CGM on blood glucose levels, body weight, BP, and hypoglycemia in patients with T2D	7 RCTs involving 669 participants: 3 involving rtCGM and 4 involving rCGM	Differences between CGM and controls in HbA1c change, body weight, BP, time in hypoglycemia < 70 mg/dL, and time in hyperglycemia > 180 mg/dL	CGM groups experienced lower HbA1c levels than controls: standard mean difference − 0.35, p = .006 for all studies pooled; − 0.45, p < .001 for rtCGM studies; − 0.43, p = 0.13 for rCGM studies. Baseline HbA1c and age were not associated with the effect of CGM on HbA1c change Time in hypoglycemia < 70 mg/dL was lower in CGM than controls, standard mean difference − 0.35 h/day, p = .006 No differences were seen between CGM and controls in time in hyperglycemia > 180 mg/dL, BP, or body weight change
Janapala, 2019 [14]	Evaluate the evidence of efficacy of CGM compared to SMBG in patients with T2D	5 RCTs involving 374 participants	Differences between CGM and controls in HbA1c change	CGM groups experienced greater HbA1c reductions than controls: standard mean difference − 0.25%, p = .01; 4 of the 5 studies favored greater HbA1c reduction in CGM than in controls, while 1 found no difference
Evans, 2020 [15]	Establish whether use of isCGM favors a reduction in HbA1c among people with T1D or T2D as a replacement for SMBG; identify whether change in HbA1c with isCGM is associated with baseline HbA1c; and determine whether HbA1c change with isCGM differs by length of study or by type of diabetes (T1D vs. T2D)	21 studies (RCTs and real-world observational studies) involving 1496 participants with T1D and 227 participants with T2D	Differences between CGM and controls in HbA1c at 2, 3, or 4 months, and up to 12 months of follow-up	Mean HbA1c change for all subjects at 2–4 months was − 0.55% (95% CI − 0.39 to − 0.70) and for adult subjects was − 0.56% (95% CI − 0.36 to − 0.76) Mean HbA1c change was associated with baseline HbA1c; for each 1% higher in mean baseline HbA1c, mean HbA1c change at follow-up changed by − 0.31% (95% CI − 0.19 to − 0.43) No significant differences in mean HbA1c change were found between adults with T1D vs. adults with T2D Where longer follow-up could be evaluated, HbA1c was found to decrease within the first 2 months, with the change sustained at 12 months
Other studies
Ish-Shalom, 2016 [16]	Evaluate use of isCGM with T2D, HbA1c ≥ 7.5%, and other factors making their diabetes “difficult-to-control”	Cross-sectional study of 31 patients using MDI therapy (25 with T2D) followed for 12 weeks with isCGM	Change in HbA1c at 8, 12, and 24 weeks	HbA1c decreased for all subjects (T1D and T2D) at 8 weeks by − 1.33% (p < .0001), and this decrease was sustained at 12 weeks in all subjects (data not reported) and at 24 weeks for those who chose to continue the device (27 of 31) by − 1.21% (p = .009) All participants reported high satisfaction, desire to continue isCGM use, that isCGM was easy to use, and that it was painless
Cox, 2016 [17]	Assess feasibility and efficacy of replacing SMBG with CGM to increase qualitative and quantitative feedback in the GEM lifestyle modification program	Pilot study of 4 adults with T2D for whom GEM was augmented with isCGM	Change in HbA1c, QoL (PAID-5)	Mean change in HbA1c was − 1.1% (from 7.8 to 6.7%), with a decrease in each participant. Despite a lower baseline mean HbA1c in this pilot, the mean HbA1c decrease was greater than in a prior pilot without CGM (− 1.0%, from 8.4 to 7.4%) Participants also experienced fewer diabetes-associated problems at follow-up, with a lower PAID-5 score post-intervention (3.3 for CGM/GEM vs. 5.8 for SMBG/GEM) and a greater decrease in PAID-5 score from baseline to post-intervention (− 3.2 for CGM/GEM vs. − 2.1 for SMBG/GEM)
Weiss, 2018 [18]	Evaluate use of isCGM and effect on HbA1c in Australia	Cross-sectional study (clinical chart audit) of 22 patients (18 with T1D and 4 with T2D) using isCGM for ≥ 2 weeks	Change in HbA1c	The overall sample experienced HbA1c change of − 1.0%, from 8.7 to 7.7% (p = .001) The T2D subset (n = 4) experienced HbA1c change of − 3.4%, from 11.9 to 8.5% (p not reported)
Hirsch, 2019 [19]	Evaluate correlations of HbA1c with CGM metrics	Meta-analysis of 4 RCTs	Correlation of HbA1c with mean glucose, GMI, TIR, time > 250 mg/dL, time < 70 mg/dL, time < 54 mg/dL	HbA1c correlated strongly with mean glucose and GMI (r = 0.80), with TIR (r = 0.75), and with time > 250 mg/dL (r = 0.72) HbA1c correlated only weakly with time < 70 mg/dL (r = 0.39) and time < 54 mg/dL (r = 0.21)
Kröger, 2020 [20]	Evaluate the impact of isCGM on HbA1c in real-world use in each of 3 European countries among patients with T2D on basal-bolus insulin therapy	Analysis of 3 cross-sectional (chart review) studies involving 363 adults (92 in Austria, 88 in France, 183 in Germany) with T2D treated with basal-bolus insulin therapy for ≥ 1 year, with isCGM use for ≥ 3 months, and with HbA1c 8.0–12.0% at baseline	Change in HbA1c from baseline (≤ 3 months before starting CGM) to 3–6 months after starting CGM use	HbA1c decreased for the pooled participants from the 3 countries, from 8.9 to 8.0% (mean change − 0.9%, p < .0001) and for each country (Austria − 0.9%, p < .0001; France − 0.8%, p < .0001; Germany − 0.9%, p < .0001). HbA1c decreased across age, sex, duration of insulin use, and BMI. Higher baseline HbA1c was associated with greater HbA1c decreases. There was no difference in HbA1c change between females vs. males, higher vs. lower BMI, or higher vs. lower age
Majithia, 2020 [21]	Evaluate glycemic outcomes associated with participation in a virtual diabetes clinic for 4 months	Prospective single-arm analysis of 55 adults with T2D and HbA1c 8.0–12.0% and not using an insulin pump, enrolled from two primary care centers into a virtual diabetes clinic including telehealth endocrinologist consultation, a proprietary app for data management, virtual engagement with an education program, diabetes education and care specialists, coaches, and rtCGM worn intermittently for 60 days of the 4-month study period	Primary: change in HbA1c from baseline Secondary: changes from baseline in TIR, time 180–250 mg/dL, time > 250 mg/dL, time < 70 mg/dL, weight	Mean change in HbA1c was –1.6%, p < .001. Greater reductions were seen for the 19 participants with baseline HbA1c > 9.0% (− 2.4%, p < .001) than for the 36 participants with baseline HbA1c 8.0–9.0% (− 1.2, p < .001) TIR increased 10.2% (p = .002), from 65.4 to 75.5% and therefore from not meeting to meeting the TIR target of > 70% Time 180–250 mg/dL decreased 7.2% (p = .005) Time > 250 mg/dL decreased 3.0% (p = .01) There was no difference in time < 70 mg/dL Weight decreased by 9.0 pounds (p < .001)
Bergenstal, 2021 [22]	Evaluate a virtual diabetes clinic’s participants’ attitudes toward remotely prescribed rtCGM and the relationship between rtCGM use and change in HbA1c	Observational study of 594 adult participants with T2D who participated in virtual diabetes clinic for CGM education and startup, used at least one provided rtCGM sensor, and with baseline HbA1c 7.7%, with mean follow-up of 10.2 months. 36.5% of respondents were treated with insulin, 25.8% were treated with sulfonylurea	CGM satisfaction and change in HbA1c from baseline	Mean CGM satisfaction score was 4.5 of 5. 94.7% of respondents agreed or strongly agreed that they were comfortable with remote CGM insertion, 97.0% agreed or strongly agreed that rtCGM use improved their understanding of the impact of eating, 95.7% agreed or strongly agreed that rtCGM use increased their knowledge, and 79.4% agreed or strongly agreed that rtCGM use helped improve their diabetes treatment even when not wearing a sensor Mean change in HbA1c was –0.6% (from 7.7% at baseline to 7.1% after a mean 10.2 months of follow-up), p < .001
Gilbert, 2021 [23]	Quantify short-term changes in glycemia and quality of life in the first few months of CGM use	Observational study of 248 adults (182 with T1D, 66 with T2D) on basal-bolus insulin therapy who had not previously used CGM	Change in HbA1c and QoL indicators (diabetes distress evaluated by DDS, hypoglycemia concerns evaluated by HABS score)	Among only the participants with T2D: HbA1c decreased by 1.4% (from 8.5 to 7.1, p < .001) Diabetes distress decreased overall and in the emotional burden, regimen distress, and interpersonal domains (all p < .001) Hypoglycemia concerns decreased overall and in the avoidance and anxiety domains (all p < .001)
Karter, 2021 [24]	Estimate clinical outcomes of initiating rtCGM	Retrospective cohort study of 41,753 people with insulin-treated diabetes (36,080 T2D, 5,673 T1D) engaging in SMBG and without prior CGM use, including 3,806 who began rtCGM and 37,947 who did not	Change in HbA1c, hypoglycemia resulting in ED visit or hospital admission; hyperglycemia resulting in ED visit or hospital admission; HbA1c < 7%; HbA1c < 8%; HbA1c > 9%; ED visit for any reason; hospital admission for any reason; number of outpatient visits; number of telephone visits	rtCGM initiators experienced greater HbA1c reduction than noninitiators (mean difference − 0.40%, p < .001). They also experienced a reduction in hypoglycemia ED visits or hospital admissions compared to an increase in noninitiators (mean difference − 2.7%, p = .001). The rtCGM cohort experienced a greater increase in proportion achieving HbA1c < 7% (mean difference 9.6%, p < .001), a greater increase in proportion achieving HbA1c < 8% (mean difference 13.1%, p < .001), a greater decrease in proportion achieving HbA1c > 9% (mean difference − 7.1%, p < .001), a greater decrease in office visits (mean difference − 0.4, p < .001), and a greater increase in telephone visits (mean difference 1.1, p < .001). There was no association found between initiating rtCGM and hyperglycemia-related ED visits or hospital admissions, ED visits for any reason, or hospital admissions for any reason

BGRI blood glucose risk index; BMI body mass index; BP blood pressure; CGM continuous glucose monitoring; CI confidence interval; CONGA continuous overall net glycemic action; CV coefficient of variation; DDS Diabetes Distress Scale; DTSQ Diabetes Treatment Satisfaction Questionnaire; ED emergency department; FPG fasting plasma glucose; GEM glycemic load, exercise, and monitoring glucose lifestyle modification program; GMI glucose management indicator; HABS Hypoglycemia Attitudes and Behavior Scale; HDL high density lipoprotein; isCGM intermittently scanned continuous glucose monitor; LADA latent autoimmune diabetes in adults; MAGE mean amplitude of glycemic excursion; MDI multiple daily injections; MODD mean of daily differences; PAID-5 Problem Areas in Diabetes 5-item short form; proCGM professional/blinded continuous glucose monitor; QoL quality of life; rCGM retrospective continuous glucose monitor; RCT randomized controlled trial; rtCGM real-time continuous glucose monitor; SD standard deviation; SMBG self-monitoring of blood glucose; T1D type 1 diabetes; T2D type 2 diabetes; TIR time in range; WHO World Health Organization