An exploratory trial of insulin initiation and titration among patients with type 2 diabetes in the primary care setting with retrospective continuous glucose monitoring as an adjunct: INITIATION study protocol.

BACKGROUND: Insulin initiation and titration in primary care is necessary to respond to the growing epidemic of type 2 diabetes (T2D). The INITIATION study aims to evaluate the impact of implementing a new model of care with Primary Care Physician and Practice Nurse (PN) teams supported by a Credentialed Diabetes Educator-Registered Nurse (CDE-RN) and endocrinologist in initiating and titrating basal and prandial insulin for T2D patients in the Australian healthcare system over 24 weeks. This study also explores the feasibility and efficacy of retrospective continuous glucose monitoring (r-CGM) in comparison with self-monitoring of blood glucose (SMBG) among people with T2D in primary care. METHODS/DESIGN: The study employs a before and after design with a nested exploratory trial of SMBG and r-CGM. A total of 102 insulin naïve T2D patients with a glycated haemoglobin (HbA1c) level of >7.5% in the previous 6 months while treated with maximal oral therapy will be recruited and screened from 22 primary care practices in Melbourne, Australia. All patients will be commenced on a basal insulin regimen following randomization into one of the two blood glucose monitoring arms, with intensification to a "basal plus" regimen if required. The outcomes of the new model of care will be benchmarked with data collected over the same period from a specialist setting in Melbourne, Australia. DISCUSSION: This article describes the study protocol and insulin treatment algorithm employed in the first study to explore r-CGM use among T2D in primary care. Findings from the INITIATION study will inform development of a larger randomized controlled trial. TRIAL REGISTRATION: ACTRN12610000797077.

Impact of quarterly professional-mode flash glucose monitoring in adults with type 2 diabetes in general practice (GP-OSMOTIC): Secondary psychological and self-care outcomes of a pragmatic, open-label, 12-month, randomised controlled trial.

AIMS: To investigate the impact of quarterly professional-mode flash glucose monitoring on psychological outcomes in adults with type 2 diabetes in primary care. METHODS: The GP-OSMOTIC trial randomised 299 adults with type 2 diabetes in 25 general practices to quarterly use of professional-mode flash glucose monitoring (sensor worn for 14 days; data discussed at clinic visit) or usual care. At baseline and 12 months, participants completed validated measures: general emotional well-being (WHO-5), diabetes-specific quality of life (DIDP), satisfaction with glucose monitoring (GME-Q), self-care activities (SDSCA) and perceived involvement in clinical care (PICS). Linear mixed-effects models examined between-group differences at 12 months. RESULTS: At 12 months, there were no clinically important between-arm differences in any secondary psychological or self-care outcomes. Per protocol analyses showed no clinically significant between-group differences. CONCLUSIONS: The GP-OSMOTIC intervention had no significant impact, at 12 months, on general emotional well-being, diabetes-specific quality of life or satisfaction with glucose monitoring, suggesting no added psychological burden. Lack of positive impact on self-reported self-care activities or perceived involvement in clinical care may warrant closer attention to the fidelity of intervention delivery, the context (e.g. the nature of clinician-patient interactions) and/or the sensitivity of the measures, as these will help plan future studies.

Use of professional-mode flash glucose monitoring, at 3-month intervals, in adults with type 2 diabetes in general practice (GP-OSMOTIC): a pragmatic, open-label, 12-month, randomised controlled trial.

BACKGROUND: Continuous glucose monitoring, either real-time (personal) or retrospective (professional mode), can identify day-to-day glucose profiles to guide management decisions for people with type 2 diabetes. We aimed to examine the effects of professional-mode flash glucose monitoring, done at 3-month intervals, in adults with type 2 diabetes in general practice. METHODS: We did a pragmatic, two-arm, open label, 12-month, individually randomised controlled trial (GP-OSMOTIC) in 25 general practices in Victoria, Australia. Eligible participants were adults aged 18-80 years, with type 2 diabetes diagnosed for at least 1 year and HbA1c at least 5·5 mmol/mol (0·5%) above their target in the past month despite being prescribed at least two non-insulin glucose-lowering drugs, insulin, or both (with therapy stable for at least 4 months). We randomly assigned participants (1:1) to either use of a professional-mode flash glucose monitoring system or usual clinical care (control). All participants wore the flash glucose monitoring sensor at baseline, and electronic randomisation (using permuted block sizes of four and six, and stratified by clinic) was done after the sensor was attached. Masking of participants and treating clinicians to group allocation was not possible, but the study statistician was masked to allocation when analysing the data. At baseline, and 3, 6, 9, and 12 months, participants in the flash glucose monitoring group wore the professional-mode flash glucose monitoring sensor for 5-14 days before their general practice visit. The sensor recorded interstitial glucose concentrations every 15 min, but the glucose data were not available to the participant until their general practice visit, where the sensor output would be uploaded to a computer by the health professional and discussed. Control group participants wore the sensor at baseline and at 12 months for data analysis only, and had usual care visits every 3 months. The primary outcome was the between-group difference in mean HbA1c at 12 months. Secondary outcomes were the between-group differences in: mean percentage time in target glucose range (4-10 mmol/L), based on ambulatory glucose profile data at 12 months; mean diabetes-specific distress (assessed with the Problem Areas In Diabetes [PAID] scale) at 12 months; and mean HbA1c at 6 months. Analysis was done by intention to treat. This trial is registered at the Australian and New Zealand Clinical Trials Registry, ACTRN12616001372471. FINDINGS: Between Oct 4, 2016, and Nov 17, 2017, we randomly assigned 299 adults: 149 to flash glucose monitoring and 150 to usual care. At 6 months, HbA1c was lower in the flash glucose monitoring group than in the usual care group (difference -0·5%, 95% CI -0·8% to -0·3%; p=0·0001). However, at 12 months (primary outcome), there was no significant between-group difference in estimated mean HbA1c (8·2% [95% CI 8·0 to 8·4] for flash glucose monitoring vs 8·5% [8·3 to 8·7] for usual care; between-group difference -0·3%, 95% CI -0·5 to 0·01; [66 mmol/mol, 95% CI 64 to 68 vs 69 mmol/mol, 67 to 72; between-group difference -3·0, 95% CI -5·0 to 0·1]; p=0·059). Mean percentage time spent in target glucose range at 12 months was 7·9% (95% CI 2·3 to 13·5) higher in the flash glucose monitoring group than in the usual care group (p=0·0060). Diabetes-specific distress PAID scores were unchanged at 12 months (between-group difference -0·7, 95% CI -3·3 to 1·9; p=0·61). No episodes of severe hypoglycaemia or treatment-related deaths were reported. One participant died during the study from causes unrelated to the intervention (following complications post-myocardial infarction with multiple comorbidities). INTERPRETATION: Professional-mode flash glucose monitoring in adults with type 2 diabetes in general practice did not improve the primary outcome of HbA1c at 12 months or diabetes-specific distress compared with usual care, but did improve time in target glucose range at 12 months and HbA1c at 6 months. Our findings suggest that professional-mode flash glucose monitoring can be implemented in a pragmatic primary care environment. Although there was no change in HbA1c at 12 months, the improved time in target range might reflect the potential of the technology to support personalised clinical care by providing insights into glycaemic profiles for some people with type 2 diabetes. FUNDING: National Health and Medical Research Council of Australia, Sanofi Australia, and Abbott Diabetes Care.

GP-OSMOTIC trial protocol: an individually randomised controlled trial to determine the effect of retrospective continuous glucose monitoring (r-CGM) on HbA1c in adults with type 2 diabetes in general practice.

INTRODUCTION: Optimal glycaemia can reduce type 2 diabetes (T2D) complications. Observing retrospective continuous glucose monitoring (r-CGM) patterns may prompt therapeutic changes but evidence for r-CGM use in T2D is limited. We describe the protocol for a randomised controlled trial (RCT) examining intermittent r-CGM use (up to 14 days every three months) in T2D in general practice (GP). METHODS AND ANALYSIS: General Practice Optimising Structured MOnitoring To achieve Improved Clinical Outcomes is a two-arm RCT asking 'does intermittent r-CGM in adults with T2D in primary care improve HbA1c?' PRIMARY OUTCOME: Absolute difference in mean HbA1c at 12 months follow-up between intervention and control arms. SECONDARY OUTCOMES: (a) r-CGM per cent time in target (4-10 mmol/L) range, at baseline and 12 months; (b) diabetes-specific distress (Problem Areas in Diabetes). ELIGIBILITY: Aged 18-80 years, T2D for ≥1 year, a (past month) HbA1c>5.5 mmol/mol (0.5%) above their individualised target while prescribed at least two non-insulin hypoglycaemic therapies and/or insulin (therapy stable for the last four months). Our general glycaemic target is 53 mmol/mol (7%) (patients with a history of severe hypoglycaemia or a recorded diagnosis of hypoglycaemia unawareness will have a target of 64 mmol/mol (8%)).Our trial compares r-CGM use and usual care. The r-CGM report summarising daily glucose patterns will be reviewed by GP and patient and inform treatment decisions. Participants in both arms are provided with 1 hour education by a specialist diabetes nurse.The sample (n=150/arm) has 80% power to detect a mean HbA1c difference of 5.5 mmol/mol (0.5%) with an SD of 14.2 (1.3%) and alpha of 0.05 (allowing for 10% clinic and 20% patient attrition). ETHICS AND DISSEMINATION: University of Melbourne Human Ethics Sub-Committee (ID 1647151.1). Dissemination will be in peer-reviewed journals, conferences and a plain-language summary for participants. TRIAL REGISTRATION NUMBER: >ACTRN12616001372471; Pre-results.

Overcoming clinical inertia in insulin initiation in primary care for patients with type 2 diabetes: 24-month follow-up of the Stepping Up cluster randomised controlled trial.

AIM: To examine the two-year impact of Stepping Up, a general practice based model of care intervention for insulin initiation and titration in Australia. METHODS: 266 participants from 74 general practices participated in the Stepping Up cluster randomised controlled trial between 2012-2014. Control practices received training in the model of care on completion of the 12-month trial. Patients were followed for 24 months. Participant baseline characteristics, insulin and non-insulin medication use were summarised for each study group. Linear mixed-effects models with random intercepts were used to estimate differences in mean outcome (HbA1c and weight) between the study groups using restricted maximum likelihood estimation. RESULTS: At baseline 61% of patients were male, mean (SD) age 62 (10) years, diabetes duration 9 (5, 13) years and mean (95% CI) HbA1c was 8.9 (8.8-9.1)% (74 (73-76)mmol/mol) for both groups. There was a significant between group difference at 6 months which was sustained at 24 months; Mean (95% CI) HbA1c at 24 months in the intervention group was 7.6 (7.5-7.8)% (60 (58-62)mmol/mol) and 8.0 (7.7-8.4)% (64 (61-68)mmol/mol) in the control group. At 24 months 97 (71.3%) of the intervention group and 26 (31.0%) of the control group were prescribed insulin; there was no significant difference in weight. Use of non-insulin anti-hyperglycaemic agents was similar in both groups with the exception of dipeptidyl peptidase-4 inhibitors which were prescribed more frequently in the control group (30(36%) vs 21(16%)). CONCLUSION: Stepping Up was associated with improved glycaemic control compared to usual care for 24 months, suggesting that the model facilitated more timely treatment intensification. Ongoing RN-CDE support may be needed to facilitate ongoing treatment intensification.

Supporting insulin initiation in type 2 diabetes in primary care: results of the Stepping Up pragmatic cluster randomised controlled clinical trial.

Objective To compare the effectiveness of a novel model of care ("Stepping Up") with usual primary care in normalising insulin initiation for type 2 diabetes, leading to improved glycated haemoglobin (HbA1c) levels.Design Cluster randomised controlled trial.Setting Primary care practices in Victoria, Australia, with a practice nurse and at least one consenting eligible patient (HbA1c ≥7.5% with maximal oral treatment).Participants 266 patients with type 2 diabetes and 74 practices (mean cluster size 4 (range 1-8) patients), followed up for 12 months.Intervention The Stepping Up model of care intervention involved theory based change in practice systems and reorientation of the roles of health professionals in the primary care diabetes team. The core components were an enhanced role for the practice nurse in leading insulin initiation and mentoring by a registered nurse with diabetes educator credentials.Main outcome measures The primary endpoint was change in HbA1c. Secondary endpoints included the proportion of participants who transitioned to insulin, proportion who achieved target HbA1c, and a change in depressive symptoms (patient health questionnaire, PHQ-9), diabetes specific distress (problem areas in diabetes scale, PAID), and generic health status (assessment of quality of life instrument, AQoL-8D).Results HbA1c improved in both arms, with a clinically significant between arm difference (mean difference -0.6%, 95% confidence interval -0.9% to -0.3%), favouring the intervention. At 12 months, in intervention practices, 105/151 (70%) of participants had started insulin, compared with 25/115 (22%) in control practices (odds ratio 8.3, 95% confidence interval 4.5 to 15.4, P<0.001). Target HbA1c (≤7% (53 mmol/mol)) was achieved by 54 (36%) intervention participants and 22 (19%) control participants (odds ratio 2.2, 1.2 to 4.3, P=0.02). Depressive symptoms did not worsen at 12 months (PHQ-9: -1.1 (3.5) v -0.1 (2.9), P=0.05). A statistically significant difference was found between arms in the mean change in mental health (AQoL mental component summary: 0.04 (SD 0.16) v -0.002 (0.13), mean difference 0.04 (95% confidence interval 0.002 to 0.08), P=0.04), favouring the intervention, but no significant difference in physical health (AQoL physical component summary: 0.03 (0.15) v 0.02 (0.13)) nor diabetes specific distress (5.6 (15.5) v -2.4 (15.4)). No severe hypoglycaemia events were reported.Conclusions The Stepping Up model of care was associated with increased insulin initiation rates in primary care, and improvements in glycated haemoglobin without worsening emotional wellbeing.Trial registration Australian and New Zealand Clinical Trials Registry ACTRN12612001028897.

An exploratory trial of basal and prandial insulin initiation and titration for type 2 diabetes in primary care with adjunct retrospective continuous glucose monitoring: INITIATION study.

AIMS: To evaluate basal and prandial insulin initiation and titration in people with type 2 diabetes mellitus (T2DM) in primary care and to explore the feasibility of retrospective-continuous glucose monitoring (r-CGM) in guiding insulin dosing. The new model of care features General Practitioners (GPs) and Practice Nurses (PNs) working in an expanded role, with Credentialed Diabetes Educator - Registered Nurse (CDE-RN) support. METHODS: Insulin-naïve T2DM patients (HbA1c >7.5% [>58 mmol/mol] despite maximal oral therapy) from 22 general practices in Victoria, Australia commenced insulin glargine, with glulisine added as required. Each was randomised to receive r-CGM or self-monitoring of blood glucose (SMBG). Glycaemic control (HbA1c) was benchmarked against specialist ambulatory patients referred for insulin initiation. RESULTS: Ninety-two patients mean age (range) 59 (28-77) years; 40% female; mean (SD) diabetes duration 10.5 (6.1) years participated. HbA1c decreased from (median (IQR)) 9.9 (8.8, 11.2)%; 85 (73, 99) mmol/mol to 7.3 (6.9, 7.8)%; 56 (52, 62) mmol/mol at 24 weeks (p < 0.0001). Comparing r-CGM (n = 46) with SMBG (n = 42), there were no differences in major hypoglycaemia (p=0.17) or ΔHbA1c (p = 0.31). More r-CGM than SMBG participants commenced glulisine (26/48 vs. 7/44; p < 0.001). Results were comparable to 82 benchmark patients, with similar low rates of major hypoglycaemia (2/89 vs. 0/82; p = 0.17) and less loss to follow up in the INITIATION group (3/92 vs. 14/82; p = 0.002). CONCLUSIONS: Insulin initiation and titration for T2DM patients in primary care was safe and improved HbA1c with low rates of major hypoglycaemia. CDE-RNs were effective in a new consultant role. r-CGM use in primary care was feasible and enhanced post-prandial hyperglycaemia recognition. Trial registration ACTRN12610000797077.

Can primary care team-based transition to insulin improve outcomes in adults with type 2 diabetes: the stepping up to insulin cluster randomized controlled trial protocol.

BACKGROUND: Type 2 diabetes (T2D) brings significant human and healthcare costs. Its progressive nature means achieving normoglycaemia is increasingly difficult, yet critical to avoiding long term vascular complications. Nearly one-half of people with T2D have glycaemic levels out of target. Insulin is effective in achieving glycaemic targets, yet initiation of insulin is often delayed, particularly in primary care. Given limited access to specialist resources and the size of the diabetes epidemic, primary care is where insulin initiation must become part of routine practice. This would also support integrated holistic care for people with diabetes. Our Stepping Up Program is based on a general practitioner (GP) and practice nurse (PN) model of care supported appropriately by endocrinologists and credentialed diabetes educator-registered nurses. Pilot work suggests the model facilitates integration of the technical work of insulin initiation within ongoing generalist care. METHODS: This protocol is for a cluster randomized controlled trial to examine the effectiveness of the Stepping Up Program to enhance the role of the GP-PN team in initiating insulin and improving glycaemic outcomes for people with T2D. 224 patients between the ages of 18 and 80 years with T2D, on two or more oral hypoglycaemic agents and with an HbA1c ≥7.5% in the last six months will be recruited from 74 general practices. The unit of randomization is the practice.Primary outcome is change in glycated haemoglobin HbA1c (measured as a continuous variable). We hypothesize that the intervention arm will achieve an absolute HbA1c mean difference of 0.5% lower than control group at 12 months follow up. Secondary outcomes include the number of participants who successfully transfer to insulin and the proportion who achieve HbA1c measurement of <7.0%. We will also collect data on patient psychosocial outcomes and healthcare utilization and costs. DISCUSSION: The study is a pragmatic translational study with important potential implications for people with T2D, healthcare professionals and funders of healthcare though making better use of scarce healthcare resources, improving timely access to therapy that can improve disease outcomes. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12612001028897.