Continuous glucose monitoring in adults with type 2 diabetes: a systematic review and meta-analysis

Aims/hypothesis: Continuous glucose monitoring (CGM) is increasingly used in the treatment of type 2 diabetes, but the effects on glycaemic control are unclear. The aim of this systematic review and meta-analysis is to provide a comprehensive overview of the effect of CGM on glycaemic control in adults with type 2 diabetes. Methods: We performed a systematic review using Embase, MEDLINE, Web of Science, Scopus and ClinicalTrials.gov from inception until 2 May 2023. We included RCTs investigating real-time CGM (rtCGM) or intermittently scanned CGM (isCGM) compared with self-monitoring of blood glucose (SMBG) in adults with type 2 diabetes. Studies with an intervention duration <6 weeks or investigating professional CGM, a combination of CGM and additional glucose-lowering treatment strategies or GlucoWatch were not eligible. Change in HbA1c and the CGM metrics time in range (TIR), time below range (TBR), time above range (TAR) and glycaemic variability were extracted. We evaluated the risk of bias using the Cochrane risk-of-bias tool version 2. Data were synthesised by performing a meta-analysis. We also explored the effects of CGM on severe hypoglycaemia and micro- and macrovascular complications. Results: We found 12 RCTs comprising 1248 participants, with eight investigating rtCGM and four isCGM. Compared with SMBG, CGM use (rtCGM or isCGM) led to a mean difference (MD) in HbA1c of −3.43 mmol/mol (−0.31%; 95% CI −4.75, −2.11, p<0.00001, I2=15%; moderate certainty). This effect was comparable in studies that included individuals using insulin with or without oral agents (MD −3.27 mmol/mol [−0.30%]; 95% CI −6.22, −0.31, p=0.03, I2=55%), and individuals using oral agents only (MD −3.22 mmol/mol [−0.29%]; 95% CI −5.39, −1.05, p=0.004, I2=0%). Use of rtCGM showed a trend towards a larger effect (MD −3.95 mmol/mol [−0.36%]; 95% CI −5.46 to −2.44, p<0.00001, I2=0%) than use of isCGM (MD −1.79 mmol/mol [−0.16%]; 95% CI −5.28, 1.69, p=0.31, I2=64%). CGM was also associated with an increase in TIR (+6.36%; 95% CI +2.48, +10.24, p=0.001, I2=9%) and a decrease in TBR (−0.66%; 95% CI −1.21, −0.12, p=0.02, I2=45%), TAR (−5.86%; 95% CI −10.88, −0.84, p=0.02, I2=37%) and glycaemic variability (−1.47%; 95% CI −2.94, −0.01, p=0.05, I2=0%). Three studies reported one or more events of severe hypoglycaemia and macrovascular complications. In comparison with SMBG, CGM use led to a non-statistically significant difference in the incidence of severe hypoglycaemia (RR 0.66, 95% CI 0.15, 3.00, p=0.57, I2=0%) and macrovascular complications (RR 1.54, 95% CI 0.42, 5.72, p=0.52, I2=29%). No trials reported data on microvascular complications. Conclusions/interpretation: CGM use compared with SMBG is associated with improvements in glycaemic control in adults with type 2 diabetes. However, all studies were open label. In addition, outcome data on incident severe hypoglycaemia and incident microvascular and macrovascular complications were scarce. Registration: This systematic review was registered on PROSPERO (ID CRD42023418005). Graphical Abstract: (Figure presented.)

Dual hormone fully closed loop in type 1 diabetes: a randomised trial in the Netherlands - study protocol

Introduction The management of type 1 diabetes (T1DM) has undergone significant advancements with the availability of novel technologies, notably continuous and flash glucose monitoring (CGM and FGM, respectively) and hybrid closed loop (HCL) therapy. The dual hormone fully closed loop (DHFCL) approach with insulin and glucagon infusion has shown promising effects in small studies on glycaemic regulation and quality of life in T1DM. Methods and analysis The Dual Hormone Fully Closed Loop for Type 1 Diabetes (DARE) study is a non-commercial 12-month open-label, two-arm randomised parallel-group trial. The primary aim of this study is to determine the long-term effects on glycaemic control, patient-reported outcome measurements and cost-effectiveness of the DHFCL compared with usual care, that is, HCL or treatment with multiple daily insulin injections+FGM/CGM. We will include 240 adult patients with T1DM in 14 hospitals in the Netherlands. Individuals will be randomised 1:1 to the DHFCL or continuation of their current care. Ethics and dissemination Ethical approval has been obtained from the Medical Research Ethics Committee NedMec, Utrecht, the Netherlands. Findings will be disseminated through peer-reviewed publications and presentations at local, national and international conferences. Trial registration number NCT05669547

SUGAR-DIP trial: Oral medication strategy versus insulin for diabetes in pregnancy, study protocol for a multicentre, open-label, non-inferiority, randomised controlled trial

Introduction In women with gestational diabetes mellitus (GDM) requiring pharmacotherapy, insulin was the established first-line treatment. More recently, oral glucose lowering drugs (OGLDs) have gained popularity as a patient-friendly, less expensive and safe alternative. Monotherapy with metformin or glibenclamide (glyburide) is incorporated in several international guidelines. In women who do not reach sufficient glucose control with OGLD monotherapy, usually insulin is added, either with or without continuation of OGLDs. No reliable data from clinical trials, however, are available on the effectiveness of a treatment strategy using all three agents, metformin, glibenclamide and insulin, in a stepwise approach, compared with insulin-only therapy for improving pregnancy outcomes. In this trial, we aim to assess the clinical effectiveness, cost-effectiveness and patient experience of a stepwise combined OGLD treatment protocol, compared with conventional insulin-based therapy for GDM. Methods The SUGAR-DIP trial is an open-label, multicentre randomised controlled non-inferiority trial. Participants are women with GDM who do not reach target glycaemic control with modification of diet, between 16 and 34 weeks of gestation. Participants will be randomised to either treatment with OGLDs, starting with metformin and supplemented as needed with glibenclamide, or randomised to treatment with insulin. In women who do not reach target glycaemic control with combined metformin and glibenclamide, glibenclamide will be substituted with insulin, while continuing metformin. The primary outcome will be the incidence of large-for-gestational-age infants (birth weight >90th percentile). Secondary outcome measures are maternal diabetes-related endpoints, obstetric complications, neonatal complications and cost-effectiveness analysis. Outcomes will be analysed according to the intention-to-treat principle. Ethics and dissemination The study protocol was approved by the Ethics Committee of the Utrecht University Medical Centre. Approval by the boards of management for all participating hospitals will be obtained. Trial results will be submitted for publication in peer-reviewed journals

The artificial pancreas, a challenge to research

The first attempts for automated glucose control were made in the seventies of the last century. Nowadays several prototypes for closed-loop glucose control are being tested, most of them in clinical research centers. Systems for automated glucose control, also named ‘artificial pancreas’ or ‘closed-loop system’ consist of three parts; the first part concerns the input or glucose measurement, the second part a mathematical model or control algorithm incorporated in a computer and the last part the output, delivery of glucose regulatory hormones, insulin and sometimes glucagon. For ambulatory human use, the system consists of subcutaneous continuous glucose monitor and subcutaneous administration of insulin and sometimes glucagon. In this thesis it is demonstrated that: - Administration of rapid-acting mealtime insulin 15 minutes before a meal resulted in better postprandial glucose control. - Mechanical occlusion of the infusion set of CSII should lead to an occlusion alert. The time to an alert differed per basal rate, length of the infusion catheter and the device. Furthermore: - A questionnaire was developed to test the intention to use the artificial pancreas. - Heart rate and acceleration as markers for exercise were used. No clear association between heart rate and acceleration and glucose values were seen because the study was too small. - Three different prototypes of a bihormonal reactive closed-loop were tested. Glucose control was feasible by using this closed loop system and significantly lower glucose values were seen in the last 24 hours of the third portable closed-loop prototype

Premeal Injection of Rapid-Acting Insulin Reduces Postprandial Glycemic Excursions in Type 1 Diabetes

OBJECTIVE-To assess the effect of three premeal timings of rapid-acting insulin on post-prandial glucose excursions in type 1 diabetes. RESEARCH DESIGN AND METHODS - Ten subjects participated in a three-way randomized crossover trial. Mean +/- SD age was 45.5 +/- 12.1 years, A1C was 8.55 +/- 1.50%, duration of diabetes was 23.8 +/- 7.8 years, and duration of continuous subcutaneous insulin infusion therapy was 8.5 +/- 6.1 years. Insulin aspart was administered at 30, 15, or 0 min before mealtime. RESULTS - Area under the curve was lower in the -15 stratum (0.41 +/- 0.51 mmol/l/min) than that in the -30 stratum (1.89 +/- 0.72 mmol/l/min, P=0.029) and 0 stratum (2.11 +/- 0.66 mmol/l/min, P=0.030). Maximum glucose excursion was lower in the -15 stratum (4.77 +/- 0.52 mmol/l) than that in the -30 (6.48 +/- 0.76 mmol/l, P=0.025) and 0 stratum (6.93 +/- 0.76 mmol/l, P=0.022). Peak glucose level was lower in the -15 stratum (9.26 +/- 0.72 mmol/l) than that in the -30 stratum (11.74 +/- 0.80 mmol/l, P=0.007) and the 0 stratum (12.29 +/- 0.93, P=0.009). Time spent in the 3.5-10 mmol/l range was higher in the -15 stratum (224.5 +/- 25.0 min) than that in the 0 stratum (90.5 +/- 23.2 min, P=0.001). There was no significant difference in occurrence of glucose levels <3.5 mmol/l between strata (P=0.901). CONCLUSIONS - Administration of rapid-acting insulin analogs 15 min before mealtime results in lower postprandial glucose excursions and more time spent in the 3.5-10.0 mmol/l range, without increased risk of hypoglycemi

Fully Closed Loop Glucose Control With a Bihormonal Artificial Pancreas in Adults With Type 1 Diabetes: An Outpatient, Randomized, Crossover Trial

OBJECTIVE: To demonstrate the performance and safety of a bihormonal (insulin and glucagon) artificial pancreas (AP) in adults with type 1 diabetes. RESEARCH DESIGN AND METHODS: In this outpatient, randomized, crossover trial, 2-week fully closed loop glucose control (AP therapy) was compared with 2-week open loop control (patient's normal insulin pump therapy with a glucose sensor if they had one). RESULTS: A total of 23 patients were included in the analysis. Time in range (70-180 mg/dL [3.9-10 mmol/L]) was significantly higher during closed loop (median 86.6% of time [interquartile range 84.9-88.5]) compared with open loop (53.9% [49.7-67.2]; P < 0.0001). CONCLUSIONS: Compared with insulin pump therapy, the bihormonal AP provided superior glucose control, without meal or exercise announcements, and was safe in adults with type 1 diabetes

Acceptance of the Artificial Pancreas: Comparing the Effect of Technology Readiness, Product Characteristics, and Social Influence Between Invited and Self-Selected Respondents

Background: Psychosocial factors that may affect acceptance of artificial pancreas (AP) systems have been investigated in small sample sizes of highly motivated, self-selected persons with type 1 diabetes (T1DM) with a focus on product characteristics. We aimed to develop a valid survey to investigate the association of technology readiness and social influence with AP acceptance in a larger sample, including both self-selected and invited respondents with T1DM. Methods: An online survey was developed based on established questionnaires. Intention to use the AP was chosen as measure of AP acceptance. T1DM patients who signed up themselves for scientific research into AP systems represented the self-selected group, while patients treated at a teaching hospital represented the invited group. Questionnaire values were compared using independent t-tests and regression analyses. Results: The developed survey showed reliability and validity. The survey was completed by 425 self-selected and 109 invited persons. Intention to use the AP was high in both groups, but was significantly higher among self-selected respondents. In both groups, intention to use the AP was most strongly related to product compatibility, followed by product complexity, technology readiness, and product usefulness among invited respondents; and followed by product usefulness and technology innovativeness among self-selected respondents. Conclusions: Product characteristics have a stronger relationship with AP acceptance than technology readiness, while social influence does not seem to be associated with AP acceptance. As the (strength of) factors differ between self-selected and invited persons, researchers and product developers should be cautious when relying on self-selected persons with T1DM in the design, development, and testing of AP systems