IMpact of flash glucose Monitoring in pEople with type 2 Diabetes Inadequately controlled with non-insulin Antihyperglycaemic ThErapy (IMMEDIATE): A randomized controlled trial.

AIM: To examine the efficacy and patient satisfaction of intermittently scanned continuous glucose monitoring (isCGM) in adults using non-insulin therapies for the management of type 2 diabetes. MATERIALS AND METHODS: The IMMEDIATE study was a multisite, open label, randomized controlled trial with follow-up at 16 weeks. Adults with type 2 diabetes using at least one non-insulin therapy, with an HbA1c of 7.5% or higher (≥ 58 mmol/mol), were randomized 1:1 to receive an isCGM device plus diabetes self-management education (isCGM + DSME) or DSME alone. Enrolment occurred from 8 September 2020 to 24 December 2021. The primary outcome was percentage mean time in range (TIR), in the final 2-week period, measured via blinded CGM. RESULTS: One hundred and sixteen participants were randomized (mean age, 58 years; diabetes duration, 10 years; mean HbA1c, 8.6% [70 mmol/mol]). At 16 weeks of follow-up, the isCGM and DSME arm had a significantly greater mean TIR by 9.9% (2.4 hours) (95% CI, -17.3% to -2.5%; P < .01), significantly less time above range by 8.1% (1.9 hours) (95% CI, 0.5% to 15.7%; P = .037), and a greater reduction in mean HbA1c by 0.3% (3 mmol/mol) (95% CI, 0% to 0.7%; P = .048) versus the DSME arm. Time below range was low and not significantly different between groups and hypoglycaemic events were few in both groups. Glucose monitoring satisfaction was higher among isCGM users (adjusted difference -0.5 [95% CI, -0.7 to -0.3], P < .01). CONCLUSIONS: The IMMEDIATE study has shown that among non-insulin-treated individuals with type 2 diabetes, use of isCGM is associated with an improvement in glycaemic outcomes.

Real-world glycaemic outcomes in adult persons with type 1 diabetes using a real-time continuous glucose monitor compared to an intermittently scanned glucose monitor: A retrospective observational study from the Canadian LMC diabetes registry (REAL-CGM-T1D).

Real-time continuous glucose monitoring (rtCGM) and intermittently scanned CGM (isCGM) have both been shown to improve glycaemic outcomes in people with T1D. The aim of this study was to compare real-world glycaemic outcomes at 6-12 months in a propensity score matched cohort of CGM naïve adults with T1D who initiated a rtCGM or an isCGM. Among the matched rtCGM and isCGM cohorts (n = 143/cohort), rtCGM users had a significantly greater HbA1c benefit compared to isCGM users (adjusted difference, -3 mmol/mol [95% CI, -5 to -1]; -0.3% [95% CI, -0.5 to -0.1]; p = 0.01). There was a significantly greater lowering of HbA1c for rtCGM compared to isCGM when baseline HbA1c was <69 mmol/mol (8.5%) (adjusted difference, -4 mmol/mol [95% CI, -7 mmol/mol to -2 mmol/mol]; -0.4% [95% CI, -0.6% to -0.2%]; p < 0.001), and in MDI users (adjusted difference, -3 mmol/mol [95% CI, -6 mmol/mol to -0 mmol/mol]; -0.3% [95% CI -0.5% to 0.0%], p = 0.04). The rtCGM cohort had significantly greater time in range (58.3 ± 16.1% vs. 54.5 ± 17.1%, p = 0.03), lower time below range (2.1 ± 2.7% vs. 6.1 ± 5.0%, p < 0.001) and lower glycaemic variability compared to the isCGM cohort. In this real-world analysis of adults with T1D, rtCGM users had a significantly greater reduction in HbA1c at 6-12 months compared to isCGM, and significantly greater time in range, lower time below range and lower glycaemic variability, compared to a matched cohort of isCGM users.

First assessment of the performance of an implantable continuous glucose monitoring system through 180 days in a primarily adolescent population with type 1 diabetes.

AIM: To investigate the performance of the Eversense XL implantable continuous glucose monitoring (CGM) system through 180 days in a primarily adolescent population with type 1 diabetes (T1D). MATERIALS AND METHODS: This prospective, single-centre, single-arm, 180-day study evaluated the effectiveness and safety of the implantable CGM system in Canadian adolescent and adult subjects with T1D. Accuracy measures included mean absolute relative difference (MARD), 15/15% agreement between CGM glucose and blood glucose measured by Yellow Springs Instruments and surveillance error grid analysis. Adolescent subjects received one sensor in the upper arm and adult subjects received one sensor in each upper arm. In-clinic CGM system accuracy studies were performed every 30 days. The safety assessment included the incidence of adverse events related to either device or the insertion/removal procedure through 180 days. RESULTS: Thirty-six subjects (30 adolescent/6 adult, 13 female/23 male, mean age 17 ± 9.2 years, mean body mass index 22 ± 4 kg/m2 ) received the CGM system. Overall MARD was 9.4% (95% CI: 8.6%-10.5%). CGM system agreement at 15/15% (N = 7163) through 60, 120 and 180 days was 82.9% (95% CI: 78.4%-86.1%), 83.6% (95% CI: 80.4%-85.7%) and 83.4% (95% CI: 79.7%-85.5%), respectively. Surveillance error grid analysis showed 98.4% of paired values in clinically acceptable error zones A and B. No insertion/removal or device-related serious adverse events were reported. CONCLUSION: The Eversense XL CGM system is safe and accurate through 180 days in a primarily adolescent population of subjects with T1D.

AWAREness of Diagnosis and Treatment of Chronic Kidney Disease in Adults With Type 2 Diabetes (AWARE-CKD in T2D).

OBJECTIVES: Diabetes remains the leading contributor to the development of chronic kidney disease (CKD) and end-stage kidney disease, emphasizing the urgency of identifying barriers to early diagnosis and intervention. The primary objective of this study was to describe the awareness, values and preferences of physicians and patients with respect to managing CKD among patients with type 2 diabetes (T2D). METHODS: A cross-sectional survey was conducted among physicians and adult patients with T2D and CKD based on estimated glomerular filtration rate and urine albumin-to-creatinine ratio (uACR) measured within 1 year. Physicians were recruited from email networks across Canada, excluding Alberta, and patients were recruited from LMC Diabetes and Endocrinology clinics in Ontario and Quebec. Two separate surveys were developed by a steering committee. Survey responses from 160 physicians (60 general practitioners, 50 endocrinologists and 50 nephrologists) and 169 patients were analyzed descriptively. RESULTS: Gaps in physician care included insufficient use of uACR screening, limited knowledge or use of Kidney Disease Improving Global Outcomes (KDIGO) and KidneyWise resources and lower than expected prescription of recommended therapies. The patient data showed 51.5% of patients were unaware of a CKD diagnosis, and 75.6% of patients who received a prior CKD diagnosis would have preferred an earlier diagnosis. CONCLUSIONS: The results highlight several opportunities for improving CKD in T2D management. More education and clarity are needed for physicians interpreting uACR levels that should prompt a referral to a nephrologist, and additional understanding of kidney risk progression is vital for patients.

Prevalence of Chronic Kidney Disease in Type 2 Diabetes: The Canadian REgistry of Chronic Kidney Disease in Diabetes Outcomes (CREDO) Study.

PURPOSE: Chronic kidney disease (CKD) in patients with type 2 diabetes (T2D) is associated with an elevated risk of end-stage kidney disease, cardiovascular disease (CVD), and death. As the breadth of treatment options for CKD in patients with T2D (CKD in T2D) continues to expand, an analysis of the current use of therapies and cardiovascular and kidney outcomes is necessary. The objectives of the study were to assess the prevalence of CKD in T2D among a contemporary cohort of patients, to describe patient characteristics and treatment patterns, and to examine health care practitioner rationale for initiating therapies. METHODS: The study was a retrospective, observational study (module A) with a prospective component (module B). For module A, sociodemographic data, medical history, prescription information, and laboratory investigations for patients seen by an endocrinologist in 2019 were retrieved from the LMC Diabetes Registry. Module B included a subset of patients for health care practitioner surveys to understand rationale for administering angiotensin-converting enzyme inhibitors (ACEis) or angiotensin receptor blockers (ARBs), steroidal mineralocorticoid receptor antagonists (MRAs), sodium-glucose cotransporter 2 inhibitors (SGLT2is), and glucagon-like peptide 1 receptor agonists (GLP-1RAs). Descriptive analyses were conducted. FINDINGS: The study included 14,873 patients (59% male). Mean patient age was 67 years, mean body mass index was 31 kg/m2, and mean glycosylated hemoglobin was 7.6%. Mean diabetes duration was 16 years. The prevalence of CKD in patients with T2D was 47.9%. Common comorbidities were hypertension (76%), dyslipidemia (71%), and obesity (51%). CVD was reported in 22%. The proportion of kidney medications and emerging therapies varied, with 76% of patients using an ACEi or ARB, 48% using an SGLT2i, 30% using a GLP-1RA, and 3% using a steroidal MRA. In module B, physicians identified that ACEis/ARBs, SGLT2is, GLP-1RAs, or steroidal MRAs were administered to primarily treat CKD in 33%, 12%, 0%, and 4% of the patients (n = 500), respectively. IMPLICATIONS: These findings improved our understanding of the current landscape and treatment patterns of CKD inT2D and highlighted the importance of considering treatments that will provide a comprehensive strategy for cardiovascular and kidney risk protection. Despite the high prevalence of CKD and comorbidities reported in a large, Canadian T2D specialist population, ACEis/ARBs, SGLT2is, and GLP-1RAs were underused, especially considering recent clinical trial reports. The relative use of steroidal MRAs was expectedly low. With an immense burden of CKD progression and among patients with T2D, the use of treatments that provide a comprehensive strategy for kidney protection will transform the landscape of CKD in T2D. ClinicalTrials.gov identifier: NCT04445181.

The impact of flash glucose monitoring on glycated hemoglobin in type 2 diabetes managed with basal insulin in Canada: A retrospective real-world chart review study.

BACKGROUND: The real-world effect of intermittently scanned continuous glucose monitoring on glucose control in type 2 diabetes treated with basal insulin is uncertain. This retrospective real-world study aimed to evaluate change in glycated hemoglobin (HbA1c) amongst adults with type 2 diabetes managed with basal insulin starting flash glucose monitoring. METHODS: Medical records were reviewed for adults with type 2 diabetes treated with basal insulin for ⩾1 year and using FreeStyle LibreTM Flash Glucose Monitoring for ⩾3 months. Prior to device use an HbA1c 8.0%-12.0% was recorded and a further HbA1c result was recorded 3-6 months (90-194 days) after starting device use. RESULTS: Medical records (n = 91) analyzed from six Canadian diabetes centers showed HbA1c significantly decreased by 0.8% ± 1.1 (mean ± SD, [p < 0.0001]) from mean baseline HbA1c 8.9% ± 0.9 to 8.1% ± 1.0 at 3-6 months after initiating flash glucose monitoring. HbA1c improvement was not independently associated with age, BMI, insulin use duration, or sex. CONCLUSION: This Canadian real-world retrospective study showed significantly reduced HbA1c following initiation of flash glucose monitoring technology to further support management of type 2 diabetes treated with basal insulin.

Persistence of GLP-1 RA in combination with basal insulin among adults with type 2 diabetes in Canada.

AIMS: The purpose of this study is to assess the persistence of Canadians with Type 2 diabetes mellitus (T2D) on loose-dose combination treatment (i.e., administered by separate devices) with a glucagon-like peptide 1 receptor agonist (GLP-1 RA) and basal insulin over 12 months. METHODS: This study is a retrospective cohort study of T2D adults using a Canadian longitudinal prescription database over a 5-year period. Cohort 1 (n = 12,411) is a primary cohort including only individuals inexperienced with the combination therapy at index. Cohort 2 (n = 13,498) is an exploratory cohort and includes everyone regardless of previous experience on the loose-dose combination therapy. The primary endpoint is the proportion of individuals persistent and average days persistent to the loose-dose combination therapy at 12 months in Canada. RESULTS: In Cohort 1, overall persistence was 47% in the 12-month period post-index. Persistence is similar when including all inexperienced and subsequent loose-dose combination experiences in Cohort 2 (45%). CONCLUSIONS: Canadian T2D adults taking a loose-dose combination therapy of a GLP-1 RA and basal insulin had overall low persistence and lower than reports from previous studies of GLP-1 RA or basal insulin alone. Improving persistence to combination therapy with GLP-1 RA plus basal insulin is an important issue to explore in clinical practice.

The Canadian LMC Diabetes Registry: A Profile of the Demographics, Management, and Outcomes of Individuals with Type 1 Diabetes.

Objective: Clinical guidelines now define the standard of diabetes care, but few health care jurisdictions systematically assess their practicality and impact. The Canadian LMC Diabetes Registry includes the electronic health records of >50 endocrinologists in three provinces and provides quarterly real-time outcome reports to each endocrinologist. This retrospective cohort study aimed to characterize the demographics, treatment regimens, and outcomes of the type 1 diabetes (T1D) patient population in the registry. Research Design and Methods: Adults were included if they had a clinical diagnosis of T1D, had seen an LMC endocrinologist between July 1, 2015 and June 30, 2018, and had follow-up >6 months. This study is registered on clinicaltrials.gov (NCT04162067). Results: The resulting cohort included 3600 individuals with mean age of 43.9 ± 15.3 years and duration of diabetes of 21.5 ± 13.9 years. Mean hemoglobin A1C (HbA1c) was 8.1% ± 1.5% and only 22.5% had achieved HbA1c ≤7.0%. In each measure, individuals in younger cohorts showed poorer glycemic control than older cohorts. Within each age cohort, insulin pump users showed a lower mean HbA1c than those using multiple daily injections, especially in cohorts who were also not using a continuous glucose monitor. Overall, 63.1% reported at least weekly hypoglycemia, whereas 3.6% reported severe hypoglycemia ≥1 per year. Conclusions: Despite receiving care in an advanced well-resourced environment, within a public health care system, from specialists armed with regular patient outcomes feedback, most individuals with T1D are unable to achieve the goals recommended by clinical practice guidelines.

Real-World Health Outcomes of Insulin Glargine 300 U/mL vs Insulin Glargine 100 U/mL in Adults With Type 1 and Type 2 Diabetes in the Canadian LMC Diabetes Patient Registry: The REALITY Study.

OBJECTIVES: This study evaluated real-world clinical outcomes of patients with type 1 diabetes (T1D) and type 2 diabetes (T2D) initiating or transferring to insulin glargine 300 U/mL (Gla-300) vs insulin glargine 100 U/mL (Gla-100). METHODS: This is a retrospective cohort study using data from the Canadian LMC Diabetes Patient Registry. The 4 following cohorts were analyzed: 1) insulin-naïve patients with T2D who initiated Gla-300 or Gla-100, 2) patients with T2D who switched from neutral protamine Hagedorn (NPH) or detemir to Gla-300 or Gla-100, 3) patients with T2D who switched from Gla-100 to Gla-300 and 4) patients with T1D who switched from Gla-100, NPH or detemir to Gla-300. RESULTS: Of 376 propensity score-matched insulin-naïve patients, 6-month reduction in glycated hemoglobin (A1C) was similar between Gla-300 (-1.78%±1.85%; p<0.001) and Gla-100 (-1.74%±1.87%; p<0.001). In 114 propensity score-matched patients who switched from NPH or detemir, 6-month reduction in A1C was similar between Gla-300 (-0.78%±1.14%) and Gla-100 (-0.70%±1.57%). The 396 patients who switched from Gla-100 to Gla-300 had a significant reduction in A1C (-0.45%±1.39%; p<0.001). In 196 patients with T1D who switched from Gla-100, NPH or detemir to Gla-300, there was a significant reduction in A1C of -0.17%±1.19% (p=0.04). CONCLUSIONS: In a real-world clinical setting, insulin-naïve patients who initiated Gla-300 or Gla-100 showed similar changes in A1C and weight. Patients with T1D or T2D using Gla-300 transferred from another basal insulin had significant reductions in A1C with no change in weight or insulin dose.

Patient Reported Outcomes following initiation of Glucagon-like peptide-1 Receptor agonists in patients with type 2 Diabetes in a specialist endocrinology practice of the LMC diabetes registry: The PROGRESS-Diabetes study.

AIMS: To compare patient-reported outcomes and clinical outcomes in patients who initiated dulaglutide or liraglutide as part of usual clinical therapy. METHODS: This observational study enrolled adults with type 2 diabetes who initiated dulaglutide or liraglutide between April 2017 and January 2018. A prospective patient cohort completed questionnaires at baseline and at their usual follow-up visit three to six months later. Clinical outcomes were assessed in a post-hoc retrospective analysis using propensity score matching. RESULTS: In the per-protocol analysis, 146 dulaglutide and 79 liraglutide patients had similar significant improvements in diabetes treatment satisfaction scores (dulaglutide 9.6 ±â€¯1.1, p < 0.001; liraglutide 10.6 ±â€¯1.4, p < 0.001) and follow-up scores for diabetes device satisfaction. Only dulaglutide had significant improvements in medication adherence scores. In the overall cohort, 754 matched patients showed similar reductions in A1C (dulaglutide -0.8% [9 mmol/mol]; liraglutide -0.7% [8 mmol/mol]). Liraglutide patients had a greater reduction in weight than those initiating dulaglutide (-2.8 kg vs. -1.8 kg; p < 0.001). CONCLUSIONS: Patients who initiated dulaglutide or liraglutide in a real-world specialist practice had similar improvements in diabetes medication satisfaction and diabetes device satisfaction. Only dulaglutide patients had significant improvements in medication adherence scores. Both treatment cohorts had similar patterns of A1C change, and liraglutide had significantly greater weight loss, which are similar to findings from clinical trials.

Overnight Glucose Control with Dual- and Single-Hormone Artificial Pancreas in Type 1 Diabetes with Hypoglycemia Unawareness: A Randomized Controlled Trial.

BACKGROUND: The dual-hormone (insulin and glucagon) artificial pancreas may be justifiable in some, but not all, patients. We sought to compare dual- and single-hormone artificial pancreas systems in patients with hypoglycemia unawareness and documented nocturnal hypoglycemia. METHODS: We conducted a randomized crossover trial comparing the efficacy of dual- and single-hormone artificial pancreas systems in controlling plasma glucose levels over the course of one night's sleep. We recruited 18 adult participants with hypoglycemia unawareness and 17 participants with hypoglycemia awareness, all of whom had documented nocturnal hypoglycemia during 2 weeks of screening. Outcomes were calculated using plasma glucose. RESULTS: In participants with hypoglycemia unawareness, the median (interquartile range [IQR]) percentage of time that plasma glucose was below 4.0 mmol/L was 0% (0-0) on dual-hormone artificial pancreas nights and 0% (0-10) on single-hormone artificial pancreas nights (P = 0.20). Additionally, participants with hypoglycemia unawareness experienced two hypoglycemic events (<3.0 mmol/L) on dual-hormone artificial pancreas nights and three hypoglycemic events on single-hormone artificial pancreas nights. In participants with hypoglycemia awareness, the median (IQR) percentage of time that plasma glucose was below 4.0 mmol/L was 0% (0-0) on both dual- and single-hormone artificial pancreas nights. Hypoglycemia awareness participants experienced zero hypoglycemic events on dual-hormone artificial pancreas nights and one event on single-hormone artificial pancreas nights. DISCUSSION: In this study, dual-hormone and single-hormone systems performed equally well in preventing nocturnal hypoglycemia in participants with hypoglycemia unawareness. Longer studies over the course of multiple days and nights may be needed to explore possible specific benefits in this population. ClinicalTrials.gov No. NCT02282254.