Development of a model of integration for complex chronic conditions across levels of healthcare and the community in Novo mesto, Slovenia.

BACKGROUND: People with complex chronic conditions have multidimensional needs and often experience fragmentation in care. A model of integration was developed based on a case study of chronic wound management in Novo mesto, Slovenia. METHODS: JA CHRODIS Recommendations and Criteria were used as a framework for developing the practice. A baseline analysis, patient needs assessments and analysis of clinical pathways were performed using qualitative methodology. RESULTS: Baseline analysis identified facilitators and barriers to care. Patient needs assessment led to organizational solutions in health and social care. Analysis of clinical pathways proved high variability in treatment process. Using these results a model of integration was developed introducing protocol of care and care coordinator at the secondary (hospital) level. CONCLUSIONS: The proposed model would significantly reduce fragmentation in care for people with complex chronic conditions. The model was discussed at the policy dialogue and action plan defined for potential sustainability and scalability of the practice.

Baseline nocturnal glucose change: A predictor of the treatment effect of bolus intensification in insulin-treated type 2 diabetes.

This post hoc analysis of an 18-week randomized trial explored the utility of calculating baseline glycated haemoglobin (HbA1c), postprandial glucose (PPG) increments and nocturnal glucose change in predicting efficacy and safety outcomes in response to bolus insulin intensification in people with type 2 diabetes (T2D). Analyses were conducted on 236 participants with T2D receiving metformin: 116 received fast-acting insulin aspart (faster aspart) basal-bolus therapy and 120 received basal-only insulin. Participants were grouped according to baseline HbA1c, PPG increments and nocturnal glucose change variables; analyses were performed on the end-of-trial treatment differences between "high" and "low" baseline values. The change from baseline in end-of-trial mean HbA1c and mean PPG increments was in favour of faster aspart across all subgroups. Significantly greater treatment differences were observed in participants with high (vs. low) baseline nocturnal glucose change and PPG increments. For baseline HbA1c, significantly greater treatment differences were observed for change in end-of-trial PPG increments, but not end-of-trial HbA1c. In conclusion, both nocturnal glucose change and PPG increments may be more useful than HbA1c for identifying subgroups of people with T2D who would most benefit from bolus intensification.

Investigating the Association Between Baseline Characteristics (HbA1c and Body Mass Index) and Clinical Outcomes of Fast-Acting Insulin Aspart in People with Diabetes: A Post Hoc Analysis.

INTRODUCTION: The aim of this study was to investigate the association between baseline characteristics [HbA1c and body mass index (BMI)] and the effect of mealtime fast-acting insulin aspart (faster aspart) relative to insulin aspart (IAsp) or basal-only insulin therapy on several efficacy and safety outcomes in people with diabetes. METHODS: Post hoc analysis of three randomised phase 3a trials in people with type 1 diabetes (T1D; onset 1) and type 2 diabetes (T2D; onset 2 and 3). Participants (N = 1686) were stratified according to baseline BMI (< 25 kg/m2, 25-< 30 kg/m2, ≥ 30 kg/m2) or HbA1c (≤ 58 mmol/mol, > 58-< 64 mmol/mol, ≥ 64 mmol/mol; ≤ 7.5%, > 7.5-< 8.0%, ≥ 8.0%). RESULTS: In participants with T2D, the estimated treatment difference for change in HbA1c was similar for all BMI and HbA1c subgroups. No major differences between treatments were observed in risk of overall hypoglycaemia or insulin dose across subgroups. In participants with T1D, change in HbA1c was similar across BMI and HbA1c subgroups, and no major differences between treatments were observed for severe or blood glucose-confirmed hypoglycaemia across subgroups. Total daily insulin dose (U/kg) was similar across all baseline HbA1c groups and the BMI < 25 kg/m2 and 25-30 kg/m2 groups, but was significantly lower with mealtime faster aspart compared with IAsp in the BMI > 30 kg/m2 subgroup. CONCLUSIONS: In participants with T1D and T2D, treatment differences (for change in HbA1c and overall hypoglycaemia) between mealtime faster aspart and insulin comparators were similar to the corresponding overall analysis across baseline HbA1c and BMI subgroups. The finding of a lower total daily insulin dose in participants with obesity (BMI > 30 kg/m2) and T1D treated with faster aspart, versus those treated with IAsp, may warrant further investigation. TRIAL REGISTRATION: ClinicalTrials.gov NCT01831765 (onset 1); NCT01819129 (onset 2); NCT01850615 (onset 3). FUNDING: Novo Nordisk A/S, Søborg, Denmark.

Adding fast-acting insulin aspart to basal insulin significantly improved glycaemic control in patients with type 2 diabetes: A randomized, 18-week, open-label, phase 3 trial (onset 3).

AIM: To confirm glycaemic control superiority of mealtime fast-acting insulin aspart (faster aspart) in a basal-bolus (BB) regimen vs basal-only insulin. MATERIALS AND METHODS: In this open-label, randomized, 18-week trial (51 sites; 6 countries), adults (n = 236) with inadequately controlled type 2 diabetes (T2D; mean glycosylated haemoglobin [HbA1c] ± SD: 7.9% ± 0.7% [63.1 ± 7.5 mmol/mol]) receiving basal insulin and oral antidiabetic drugs underwent 8-week optimization of prior once-daily basal insulin followed by randomization 1:1 to either a BB regimen with faster aspart (n = 116) or continuation of once-daily basal insulin (n = 120), both with metformin. Primary endpoint was HbA1c change from baseline after 18 weeks of treatment. Secondary endpoints included: postprandial plasma glucose (PPG) change and overall PPG increment (all meals); weight; treatment-emergent adverse events; hypoglycaemic episodes. RESULTS: HbA1c decreased from 7.9% (63.2 mmol/mol) to 6.8% (50.7 mmol/mol; BB group) and from 7.9% (63.2 mmol/mol) to 7.7% (60.7 mmol/mol; basal-only group); estimated treatment difference [95% confidence interval] -0.94% [-1.17; -0.72]; -10.3 mmol/mol [-12.8; -7.8]; P < .0001. Reductions from baseline in overall mean 2-hour PPG and overall PPG increment for all meals (self-measured plasma glucose profiles) were statistically significant in favour of BB treatment ( P < .0001). Severe/blood glucose confirmed hypoglycaemia rate (12.8 vs 2.0 episodes per patient-years of exposure), total daily insulin (1.2 vs 0.6 U/kg) and weight gain (1.8 vs 0.2 kg) were greater with BB than with basal-only treatment. CONCLUSIONS: In T2D, faster aspart in a BB regimen provided superior glycaemic control as compared with basal-only insulin, but with an increase in the frequency of hypoglycaemia and modest weight gain.

Efficacy and safety of once-weekly semaglutide versus once-daily insulin glargine as add-on to metformin (with or without sulfonylureas) in insulin-naive patients with type 2 diabetes (SUSTAIN 4): a randomised, open-label, parallel-group, multicentre, multinational, phase 3a trial.

BACKGROUND: Several pharmacological treatment options are available for type 2 diabetes; however, many patients do not achieve optimum glycaemic control and therefore new therapies are necessary. We assessed the efficacy and safety of semaglutide, a glucagon-like peptide-1 (GLP-1) analogue in clinical development, compared with insulin glargine in patients with type 2 diabetes who were inadequately controlled with metformin (with or without sulfonylureas). METHODS: We did a randomised, open-label, non-inferiority, parallel-group, multicentre, multinational, phase 3a trial (SUSTAIN 4) at 196 sites in 14 countries. Eligible participants were insulin-naive patients with type 2 diabetes, aged 18 years and older, who had insufficient glycaemic control with metformin either alone or in combination with a sulfonylurea. We randomly assigned participants (1:1:1) to either subcutaneous once-weekly 0·5 mg or 1·0 mg semaglutide (doses reached after following a fixed dose-escalation regimen) or once-daily insulin glargine (starting dose 10 IU per day, then titrated weekly to a pre-breakfast self-measured plasma glucose target of 4·0-5·5 mmol/L [72-99 mg/dL]) for 30 weeks. In all treatment groups, previous background metformin and sulfonylurea treatment was continued throughout the trial. We did the randomisation using an interactive voice or web response system. The primary endpoint was change in mean HbA1c from baseline to week 30 and the confirmatory secondary endpoint was the change in mean bodyweight from baseline to week 30. We assessed efficacy and safety in the modified intention-to-treat population (mITT; all randomly assigned participants who were exposed to at least one dose of study drug) and used a margin of 0·3% to establish non-inferiority in HbA1c reduction. This trial is registered with ClinicalTrials.gov, number NCT02128932. FINDINGS: Between Aug 4, 2014, and Sept 3, 2015, we randomly assigned 1089 participants to treatment; the mITT population consisted of 362 participants assigned to 0·5 mg semaglutide, 360 to 1·0 mg semaglutide, and 360 to insulin glargine. 49 (14%) participants assigned to 0·5 mg semaglutide discontinued treatment prematurely, compared with 55 (15%) assigned to 1·0 mg semaglutide, and 26 (7%) assigned to insulin glargine. Most discontinuations were due to adverse events-mostly gastrointestinal with semaglutide, and others such as skin and subcutaneous tissue disorders (eg, rash, pruritus, and urticaria) with insulin glargine. From a mean baseline HbA1c of 8·17% (SD 0·89), at week 30, 0·5 and 1·0 mg semaglutide achieved reductions of 1·21% (95% CI 1·10-1·31) and 1·64% (1·54-1·74), respectively, versus 0·83% (0·73-0·93) with insulin glargine; estimated treatment difference versus insulin glargine -0·38% (95% CI -0·52 to -0·24) with 0·5 mg semaglutide and -0·81% (-0·96 to -0·67) with 1·0 mg semaglutide (both p<0·0001). Mean bodyweight at baseline was 93·45 kg (SD 21·79); at week 30, 0·5 and 1·0 mg semaglutide achieved weight losses of 3·47 kg (95% CI 3·00-3·93) and 5·17 kg (4·71-5·66), respectively, versus a weight gain of 1·15 kg (0·70-1·61) with insulin glargine; estimated treatment difference versus insulin glargine -4·62 kg (95% CI -5·27 to -3·96) with 0·5 mg semaglutide and -6·33 kg (-6·99 to -5·67) with 1·0 mg semaglutide (both p<0·0001). Severe or blood glucose-confirmed hypoglycaemia was reported by 16 (4%) participants with 0·5 mg semaglutide and 20 (6%) with 1·0 mg semaglutide versus 38 (11%) with insulin glargine (p=0·0021 and p=0·0202 for 0·5 mg and 1·0 mg semaglutide vs insulin glargine, respectively). Severe hypoglycaemia was reported by two (<1%) participants with 0·5 mg semaglutide, five (1%) with 1·0 mg semaglutide, and five (1%) with insulin glargine. Six deaths were reported: four (1%) in the 0·5 mg semaglutide group (three cardiovascular deaths, one pancreatic carcinoma, which was assessed as being possibly related to study medication) and two (<1%) in the insulin glargine group (both cardiovascular death). The most frequently reported adverse events were nausea with semaglutide, reported in 77 (21%) patients with 0·5 mg and in 80 (22%) with 1·0 mg, and nasopharyngitis reported in 44 (12%) patients with insulin glargine. INTERPRETATION: Compared with insulin glargine, semaglutide resulted in greater reductions in HbA1c and weight, with fewer hypoglycaemic episodes, and was well tolerated, with a safety profile similar to that of other GLP-1 receptor agonists. FUNDING: Novo Nordisk A/S.

Implementing an optimized glucose-lowering strategy with a novel once daily modified release gliclazide formulation.

AIM: The 6-months titration profile of a new scored gliclazide modified release (MR) formulation (MR 60 mg) was explored in individuals with type 2 diabetes. METHODS: This international study enrolled 7170 individuals, age ≥ 35 years with HbA1c ≥ 7.5% (59 mmol/mol) and not on insulin. Participants were started on 30-120 mg gliclazide MR 60 mg once daily as a first line (FIRST), add-on (ADD) or switch from a previous oral antihyperglycemic treatment strategy (SWITCH). Uptitration was capped at 120 mg. RESULTS: Women comprised 58.5% of the cohort. Mean baseline age was 58.9 years, body mass index 30.1 kg/m(2) and diabetes duration 5.1 years. Mean baseline HbA1c for the FIRST (n=2023), ADD (n=3136) and SWITCH (n=1834) groups was 8.9% (74 mmol/mol), 8.8% (73 mmol/mol) and 8.8% (73 mmol/mol), respectively. Probability of reaching optimal dose at months 1, 2, 3 and 6 was 15%, 39%, 59% and 92%, respectively. Mean HbA1c changes from baseline to month 6 were FIRST: -1.98%, ADD: -1.74% and SWITCH: -1.61% (all p<0.01). Overall, 65.3% achieved HbA1c ≤ 7.0% (53 mmol/mol); average duration for achieving glucose control was 80.1 days. Mean weight loss ranged from -1.45 to -1.27 kg. Severe hypoglycemia was experienced by 0.06% of participants. Most (95.5%) indicated a greater likelihood of adherence with the gliclazide MR 60 mg regime relative to their previous therapy. CONCLUSIONS: In this large, real world study, progressive uptitration with gliclazide MR 60 mg once daily appears to be efficacious and safe in individuals with suboptimal glycemic control at various stages of the diabetes continuum.

National Diabetes Plans: can they support changes in health care systems to strengthen diabetes prevention and care?

Healthcare systems do not fit well with the "modern" patient, who has a right to autonomy and self-determination. The services that are designed and delivered in policy contexts are not prone to encourage innovation. National Diabetes Plans, defined as "any formal strategy for improving diabetes policy, services and outcomes that encompass structured and integrated or linked activities which are planned and co-ordinated nationally and conducted at the national, regional, and local level", may hold a great potential not only to improve prevention and care for type 2 diabetes, but also for transforming healthcare delivery. Today, changes to adapt healthcare delivery tend to be implemented within existing provider structures, with limited understanding of specific context, structures, processes and potential for change. National Diabetes Plan can be a diagnostic tool for barriers, can be a driver for planning the change, and can help develop capacities and competences that are needed to strengthen healthcare systems to better address health promotion and chronic diseases.