Effectiveness and Safety of an Advanced Hybrid Closed-Loop System in Adolescents and Adults with Type 1 Diabetes Previously Treated with Continuous Subcutaneous Insulin Infusion and Flash Glucose Monitoring

Abstract

This study aimed to evaluate the effectiveness and safety of the MiniMed™ 780G advanced hybrid closed-loop (AHCL) system in people with type 1 diabetes (T1D) previously treated with continuous subcutaneous insulin infusion combined with flash glucose monitoring in a real-life setting. A total of 47 subjects (mean age 41 ± 13.6 years, 60% females, diabetes duration 28 ± 11 years) were included and switched to an AHCL system. Baseline and 6-month data were analyzed. Time in range 70–180 mg/dL increased from 65.3% at baseline to 73.8% at 6 months. Time in hyperglycemia >180 mg/dL decreased from 26.6% to 19.3%. Time in hypoglycemia <70 mg/dL decreased from 4.6% to 2.3%. The coefficient of variation also decreased from 36% to 31.6%. No episodes of severe hypoglycemia, diabetes ketoacidosis, or diabetes-related hospital admissions occurred. In conclusion, the MiniMed 780G AHCL system enables the safe achievement of recommended glycemic targets in people with T1D after 6 months of use.

Introduction

Continual advances in diabetes technology offer the potential to optimize diabetes care. Several real-world studies have demonstrated that flash or intermittently scanned continuous glucose monitoring (isCGM) combined with continuous subcutaneous insulin infusion (CSII) is associated with improved glycemic control in terms of HbA1c.^1,2 However, recommended glycemic targets of time in range (TIR), time below range (TBR), time above range (TAR), and glycemic variability³ are only achieved by a small percentage of patients. It has been reported that <5% of individuals with type 1 diabetes (T1D) treated with CSII and isCGM are able to meet the following criteria: glucose management indicator (GMI) ≤7%, >70% TIR, <25% TAR, <4% TBR, and coefficient of variation (CV) <36%.⁴

Advances in diabetes technology in recent years have enabled the development of integrated sensor-augmented pump systems that automate insulin delivery. The simplest form, achieved with low-glucose suspend systems, has evolved to the so-called hybrid closed-loop or artificial pancreas systems. They include a control algorithm that responds in real time to changes in sensor glucose levels and adjusts the subcutaneous insulin infusion delivered by the insulin pump.⁵ Ongoing progress in the automation of insulin delivery has led to an improvement in glycemic control and a reduction in time in hypoglycemia. In fact, artificial pancreas systems have been the first to enable the majority of people with T1D to achieve TIR and TBR targets, in both clinical trials and real-world settings.

The Medtronic MiniMed™ 780G advanced hybrid closed-loop (AHCL) system is a new generation of artificial pancreas systems. The technology includes automatic basal insulin delivery every 5 min, adjustable to targets of 100, 110, and 120 mg/dL, and automatic correction boluses to a fixed glucose target of 120 mg/dL.⁶ Meal announcement by the patient is required for optimal glycemic results. The pivotal trial, conducted in adolescents and adults with T1D, demonstrated an improvement in TIR from 68.8% to 74.5% and a reduction in HbA1c from 7.5% to 7%, after 3 months of AHCL use.⁷

When using the optimal system settings of a 100 mg/dL glucose target and active insulin time (AIT) of 2 h, TIR increased to 78.8%. Real-world analyses of data uploaded to CareLink personal software have also shown improved outcomes, with most users achieving TIR >70% and GMI <7%, while minimizing hypoglycemia.^8,9 In addition, a rapid improvement in TIR from 67.3% to 79.6% has been described in T1D subjects who were switched to AHCL from sensor-augmented pump therapy with predictive low-glucose suspend (SAP-PLGS).¹⁰

Our study aimed to evaluate the effectiveness and safety of the Medtronic MiniMed 780G AHCL system in people with T1D treated with CSII and isCGM in real-life clinical practice.

Materials and Methods

Study population

The study population included consecutive individuals with T1D receiving combined treatment with CSII (MiniMed 640G) and isCGM (Free Style Libre 2) who were switched to the MiniMed 780G AHCL system between March 2021 and November 2021. All the patients were seen at the outpatient clinic of a tertiary hospital, followed by a multidisciplinary team, composed by endocrinologists and diabetes nurses. Inclusion criteria were age >14 years, having T1D for >1 year, and treatment with CSII and isCGM for at least 6 months before inclusion. Pregnant women and patients who used a different CGM system were excluded.

Study design

This was an observational real-world study, based on data retrieved from charts as part of clinical care for 6-month follow-up. All the procedures were conducted as part of standard care with no additional research intervention. The decision to use an AHCL was made before and independent of their entrance to the study.

Two training sessions were conducted (one virtual and one face-to-face). Auto Mode was initiated after 7–14 days of Manual Mode. Automatic correction was activated, and a glucose target of 100 mg/dL and an AIT of 3 h were set for all the participants. The configuration of the MiniMed 780G parameters was part of the routine clinical practice and was not controlled by the investigators.

The study protocol followed the Declaration of Helsinki. All the participants were informed of the study and signed a consent form.

Outcomes

The primary endpoint was the change in the percentage of time spent in the glucose range of 70–180 mg/dL at 6 months. Secondary outcomes included (1) change in other parameters of glucose control at 6 months: time in hyperglycemia (>180 and >250 mg/dL), time in hypoglycemia (<70 and <54 mg/dL), mean glucose levels, glycemic variability measured by CV, GMI, and HbA1c; (2) change in insulin doses; (3) safety: episodes of severe hypoglycemia, diabetic ketoacidosis, and diabetes-related hospital admissions; (4) hypoglycemia awareness (Clarke score), and (5) patient-reported outcomes in terms of treatment satisfaction.

Data collection

Glycemic outcomes at baseline and after 6 months of AHCL use were analyzed. Glycated hemoglobin was measured using methods certified by the National Glycohemoglobin Standardization Program. Baseline sensor and insulin pump data were downloaded using the Libreview and Carelink System platforms, respectively. At 6 months, the last 2 weeks of 780G sensor and insulin data were downloaded using the CareLink System platform. The following data from the downloads were collected and evaluated: TIR 70–180 mg/dL, time <70 and <54 mg/dL, time >180 and >250 mg/dL and CV. Daily insulin dose and the amount of insulin given as an automatic correction, time in Auto Mode, the number of exits from Auto Mode, and the reasons for the exits were also evaluated.

In addition, participants were asked to complete the Clarke score at baseline and at the 6-month visit. The Clarke score comprises eight questions assessing patient experience during hypoglycemic events; a score ≥4 suggests impaired awareness of hypoglycemia.¹¹ Treatment satisfaction was evaluated using the Diabetes Treatment Satisfaction Questionnaire (DTSQc) at 6 months. DTSQc scores range from −18 to +18, with higher scores indicating greater satisfaction.¹²

Statistical analysis

Data were analyzed using SPSS Statistics software, version 25. Results are presented as mean ± SD values in normal distributions or as median (interquartile range) in non-normal distributions. A Wilcoxon signed-rank test was performed to analyze differences in the non-normal distributions, and the paired t-test was used in the normal distributions. Correlation analyses were performed using Spearman's correlation coefficient. A chi-square test was used to perform a bivariate analysis. A P-value <0.05 was considered statistically significant. P-values were adjusted using the Benjamini–Hochberg correction for multiple comparisons, with the software R.

Results

The study population comprised a total of 47 adolescents and adults with T1D. Median age was 41 ± 13.6 years (range 16–60 years), 60% were female, 100% were Caucasians, and mean diabetes duration was 28 ± 11 years (range 6–66 years). The mean duration of CSII and isCGM before the study was 6 ± 3 and 2 ± 1.3 years, respectively.

Glycemic outcomes

TIR 70–180 mg/dL increased from 65.3% (54–81) at baseline to 73.8% (65–85) at 6 months (P = 0.001). This improvement was due to a reduction in time in hyperglycemia, from 26.6% (12–38) at baseline to 19.3% (9.29) at 6 months. Time in hypoglycemia <70 mg/dL also decreased from 4.6% (1.7) at baseline to 2.3% (1–3) at 6 months. An improvement in glycemic variability was also observed, with a reduction in the CV from 36% ± 8.2% at baseline to 31.6% ± 3.6% at 6 months. GMI and mean sensor glucose also decreased from 6.8% (6–7) at baseline to 6.6% (6–7) at 6 months and from 151.8 mg/dL (132–174) to 141.7 mg/dL (128–152), respectively. In addition, an improvement in HbA1c was found, with a reduction from 7.2% (7–8) at baseline to 7.1% (7–8) at the end of the study. However, after adjustment for multiplicity, we found no statistically significant differences in HbA1c (Table 1 and Fig. 1).

FIG. 1.

Comparison of TIR 70–180 mg/dL at baseline (with CSII and flash glucose monitoring) and after 6 months of use of the MiniMed™ 780G AHCL system. AHCL, advanced hybrid closed-loop; CSII, continuous subcutaneous insulin infusion; TIR, time in range.

Table 1.

Glycemic Outcomes and System Usability After 6 Months of Use of an Advanced Hybrid Closed-Loop System Compared with Baseline (Continuous Subcutaneous Insulin Infusion and Flash Glucose Monitoring)

	Baseline (CSII+isCGM)	6 months (AHCL)	P	P-adjusted^a
Glycemic outcomes
Time 70–180 mg/dL (%), median (IQR)^b	65.3 (54–81)	73.8 (65–85)	0.001	0.005
Time >180 mg/dL (%), median (IQR)^b	26.6 (12–38)	19.3 (9–29)	0.009	0.016
Time >250 mg/dL (%), median (IQR)^b	1 (0–7)	2 (1–5)	0.888	0.888
Time <70 mg/dL (%), median (IQR)^b	4.6 (1–7)	2.3 (1–3)	0.002	0.006
Time <54 mg/dL (%), median (IQR)^b	0 (0–1)	0 (0–1)	0.771	0.867
Mean glucose (mg/dL), median (IQR)^b	151.8 (132–174)	141.7 (128–152)	0.004	0.009
GMI (%), median (IQR)^b	6.8 (6–7)	6.6 (6–7)	0.145	0.186
HbA1c (%), median (IQR)^b	7.2 (7–8)	7.1 (7–8)	0.035	0.052
CV of glucose (%), mean ± SD^c	36.0 ± 8.2	31.6 ± 3.6	0.001	0.005
Parameters of use
Total daily insulin (U/day), mean ± SD^c	36.2 ± 14.8	40.2 ± 20.8	0.210	0.210
Total basal insulin (U/day), mean ± SD^c	19.1 ± 7.7	18.1 ± 11.2	0.005	0.008
Total basal insulin (%), mean ± SD^c	54.7 ± 14.5	44.5 ± 8.1	<0.001	<0.001
Total bolus insulin (U/day), mean ± SD^c	16.9 ± 9.7	22.1 ± 10.8	0.046	0.057
Total bolus insulin (%), mean ± SD^c	45.3 ± 14.5	55.4 ± 8.1	<0.001	<0.001
Auto correction boluses (U/day), mean ± SD		5.9 ± 9.4
Auto correction boluses (%), mean ± SD		21.0 ± 12.7
Carbohydrate intake (g/day), mean ± SD		104.0 ± 78.9
Active insulin (h), mean ± SD		2.8 ± 0.6
Sensor calibrations (n/day), mean ± SD		4.2 ± 3.4
Sensor use (%), mean ± SD		88.9 ± 12.8
Time in auto mode (%), mean ± SD		92.5 ± 16.0

Bold values denote statistical significance at the p < 0.05 level.

^a p-Adjusted by multiple comparisons—Benjamini and Hochberg.

Wilcoxon signed-rank test.

Paired t-test.

AHCL, advanced hybrid closed-loop; CSII, continuous subcutaneous insulin infusion; CV, coefficient of variation; GMI, glucose management indicator; IQR, interquartile range; isCGM, intermittently scanned continuous glucose monitoring; SD, standard deviation.

The percentage of individuals achieving the recommended TIR 70–180 mg/dL of >70% and TBR <70 mg/dL of <4% increased from 41.4% at baseline to 60.9% at 6 months and from 46.3% at baseline to 80.5% at 6 months, respectively. The percentage of individuals achieving both recommendations, TIR 70–180 mg/dL of >70% and TBR <70 mg/dL of <4%, increased from 21.9% at baseline to 51.2% at 6 months. Similarly, the proportion of users achieving the recommended CV target of <36% increased from 55% at baseline to 85% at 6 months. Moreover, most of the subjects (47.2%) achieved an increase in TIR together with a reduction in TBR, and 43.2% of them achieved a reduction in TAR with a reduction in TBR (Fig. 2).

FIG. 2.

(A) Change in %TIR (70–180 mg/dL) versus change in %TBR (<70 mg/dL); (B) Change in %TAR (>180 mg/dL) versus change in %TBR (<70 mg/dL) after 6 months of use of the MiniMed 780G AHCL system. TAR, time above range; TBR, time below range.

Users with the lowest TIR pre-AHCL (TIR <56%), achieved the best improvement in TIR, from 43.3% (27–55) at baseline to 62.6% (37–85) at 6 months.

System usability

At 6 months, time in Auto Mode was 92.5% ± 16%. The main reason for the system exiting Auto Mode to Manual Mode was “Auto Mode disabled by the user.” An average of 4.2 ± 3.4 sensor calibrations per day was performed.

The mean total daily insulin dose (TDD) increased from 36.2 ± 14.8 U at baseline (with CSII and isCGM) to 40.2 ± 20.8 U after 6 months of AHCL use. This was mainly driven by bolus insulin, which increased from 45.3% ± 14.5% to 55.4% ± 8.1% of the TDD. At 6 months, automatic correction boluses accounted for 5.9 ± 9.4 U of insulin per day, representing 21% ± 12.7% of total boluses (Table 1). A negative correlation was found between the percentage of automatic correction doses of insulin and TIR 70–180 mg/dL (r − 0.44, P = 0.002). A significant positive correlation was found between the percentage of automatic correction doses and GMI (r − 0.81, P < 0.001).

Safety

There were no episodes of severe hypoglycemia, diabetic ketoacidosis, or diabetes-related hospital admissions during the study.

Patient-reported outcomes

The Clarke score decreased from 3 (1–5) at baseline to 2 (0–4) at 6 months (P = 0.002), which could represent an improvement in the awareness of hypoglycemia.

After 6 months of AHCL use, the participants reported a DTSQc score of 15.3 ± 3.3, out of a maximum score of 18, indicating high treatment satisfaction.

Discussion

isCGM has been shown to improve glycemic control in people with T1D treated with multiple daily injections or CSII.¹³ However, even with isCGM, the glycemic targets recommended by the International Consensus of TIR³ are often difficult to achieve. In this study, after implementing the Medtronic MiniMed 780G system in a real-life setting, we demonstrated that adolescents and adults with T1D previously treated with CSII and isCGM can safely improve their glycemic control. Our data show beneficial effects on glycemic outcomes 6 months after transitioning to this system, including increased TIR 70–180 mg/dL and decreased time in hypoglycemia, time in hyperglycemia, GMI, and glycemic variability.

To the best of our knowledge, this study represents the first real-world assessment of the effectiveness and safety of the MiniMed 780G AHCL system in people with T1D previously treated with CSII and isCGM. Recent real-world studies have examined the performance of the MiniMed 780G in subjects who switched from SAP-PLGS to AHCL. Beato-Víbora et al reported an immediate improvement in TIR (70–180 mg/dL) from 67.3% to 79.6% in the first month after the initiation of the MiniMed 780G system in adolescents and adults with T1D.¹⁰ No differences in time in hypoglycemia <70 and <54 mg/dL or glycemic variability were seen at 1 month.¹⁰ Benefits in terms of glycemic control were sustained after 3 months of using the system.¹⁴ These findings are consistent with those of previous trials of the MiniMed 780G.^7,15,16 In addition, Da Silva et al reported an increase in TIR from 63.4% to 75.5% in 812 users with >10 days of sensor glucose data after initiating AHCL.⁸

In our study, the mean TIR (70–180 mg/dL) achieved was 73.8% after 6 months of use of the 780G system. The better results in TIR obtained by Beato-Víbora et al (79.6% at 1 month and 80.1% at 3 months) may be related to more aggressive settings of the system from the beginning, that is, an algorithm glucose target of 100 mg/dL and 2 h of AIT.^10,14 In the pivotal trial, the best outcomes in TIR were also obtained with the most aggressive settings.⁷ However, even with less aggressive settings (glucose target of 100 mg/dL, but 2.8 ± 0.6 h of AIT at 6 months), in our study, 60.9% and 80.4% of the individuals were able to reach the targets of TIR (70–180 mg/dL) >70% and TBR <70 mg/dL <4%, respectively.

In contrast to Beato-Víbora et al, we found a reduction in time in hypoglycemia (both TBR <70 and TBR <54) and glycemic variability. This is probably due to differences in baseline therapy since they included well-controlled and experienced SAP-PLGS users.¹⁰ This reduction in time in hypoglycemia may explain the fact that we found no differences in HbA1c, despite the 8% increase in TIR. In addition, in our study, the Clarke score decreased from 3 (1–5) at baseline to 2 (0–4) at 6 months. Previous studies have failed to demonstrate an improvement in counter-regulatory hormonal responses in individuals with impaired awareness of hypoglycemia with the use of a closed-loop system.¹⁷ However, in our study, better self-reported hypoglycemia awareness, and less time spent in hypoglycemia suggest the potential benefits of the MiniMed 780G AHCL system in people with impaired awareness of hypoglycemia.

Previous studies with closed loop systems have reported larger improvements in glycemic control in populations with lower baseline in TIR.¹⁸ We have shown similar results, suggesting that AHCL could be prioritized to those people with the lowest TIR.

As previously described with the use of the MiniMed 780G AHCL system,^7,10 the improvement in glucose control shown in our study was achieved in a safe manner, without episodes of severe hypoglycemia, diabetic ketoacidosis, or diabetes-related hospital admissions. Contrary to what Petrovski et al described with the use of MiniMed 670G HCL system in real life¹⁹ no hyperglycemia events requiring supervision or assistance by a health care professional were recorded during the follow-up time in our study.

We acknowledge several limitations of our study: the small sample size, the lack of a control group, the use of different CGM systems (FreeStyle Libre 2 at baseline, and Guardian 3 afterward), as well as the lack of information on glycemic results with more aggressive settings. In fact, some P-values should be interpreted with caution due to the comparison of two different CGM systems. Despite these limitations, this study provides insight into the effectiveness and safety of an AHCL system in subjects with TD1 treated with CSII and isCGM in a real-life setting.

Conclusion

In conclusion, in a real-world clinical setting, the MiniMed 780G AHCL system provides sustained improvement in glycemic outcomes in a safe manner in adolescents and adults previously treated with CSII and isCGM.

Footnotes

Authors' Contributions

N.G.H., S.A., and V.B. wrote the initial research proposal, reviewed the proposal and the study results, and wrote the article. G.L.G., F.L., A.P.M, C.A.R.T., and A.S.M. reviewed and edited the research proposal and article, and contributed to the discussion. All authors read and approved the final version of this article.

Acknowledgments

The authors would like to thank the Methodological and Statistical Support Unit (UAME) of Hospital Universitario Virgen del Rocío for their support.

Author Disclosure Statement

No competing financial interests exist.

Funding Information

No funding was received for this article.

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