Basal insulin initiation in primary vs. specialist care: similar glycaemic control in two different patient populations.

OBJECTIVE: To investigate the effect of healthcare provider (HCP) type (primary vs. specialist) on glycaemic control and other treatment parameters. RESEARCH DESIGN AND METHODS: Study of Once-Daily Levemir (SOLVE(™) ) is an international, 24-week, observational study of insulin initiation in people with type 2 diabetes. RESULTS: A total of 17,374 subjects were included, comprising 4144 (23.9%) primary care subjects. Glycaemic control improved in both HCP groups from baseline to final visit [glycated haemoglobin (HbA1c) -1.2 ± 1.4% (-13.1 ± 15.3 mmol/mol) and -1.3 ± 1.6% (-14.2 ± 17.5 mmol/mol), respectively]. After adjustment for known confounders, there was no statistically significant effect of HCP group on final HbA1c [-0.04%, 95% confidence interval (CI) -0.09 to -0.01 (-0.4 mmol/mol, 95% CI -1.0-0.1 mmol/mol), p = 0.1590]. However, insulin doses at the final visit were higher in primary care patients (+0.06, 95% CI 0.06-0.07 U/kg, p < 0.0001). Logistic regression demonstrated a significant effect of HCP type (primary vs. specialist care) on hypoglycaemia risk [odds ratio (OR) 0.75, 95% CI 0.64-0.87, p = 0.0002]. Primary care physicians took more time to train patients and had more frequent contact with patients than specialists (both p < 0.0001). CONCLUSIONS: Primary care physicians and specialists achieved comparable improvements in glycaemic control following insulin initiation.

Insulin degludec/insulin aspart produces a dose-proportional glucose-lowering effect in subjects with type 1 diabetes mellitus.

AIMS: To evaluate the pharmacodynamic dose-response relationship of insulin degludec/insulin aspart (IDegAsp), a novel, soluble co-formulation of the ultra-long-acting basal insulin, insulin degludec (IDeg), with the rapid-acting prandial insulin (IAsp), across different doses in patients with type 1 diabetes (T1DM). METHODS: This was a randomized, single-centre, double-blind, four-period, incomplete block, crossover trial. A cohort of 33 people with T1DM received single doses (0.4, 0.6 or 0.8 U/kg) of IDegAsp or the comparator, biphasic insulin aspart 30, in a randomized sequence of four treatment periods, each separated by a washout of 13-21 days. Pharmacodynamic response was assessed using a 26-h euglycaemic glucose clamp, with blood glucose stabilized at a target of 5.5 mmol/l (100 mg/dl). RESULTS: A rapid onset of action and a distinct peak attributable to IAsp was observed in the glucose infusion rate (GIR) profile, followed by a separate, flat and stable basal glucose-lowering effect attributable to the IDeg component. The mean area under the GIR curve over 24 h (AUC(GIR,0-24 h)), and the mean maximum GIR (GIR(max)) increased with increasing dose level of IDegAsp. A dose-response relationship for IDegAsp was demonstrated for AUC(GIR,0-24 h) and GIR(max), indicating dose proportionality. A dose-concentration relationship was also observed for both the basal and bolus components of IDegAsp. CONCLUSIONS: IDegAsp has a clear dose-response relationship, indicating the clinical potential for straightforward titration according to individual patient needs.

Effect of once-daily insulin detemir on oral antidiabetic drug (OAD) use in patients with type 2 diabetes.

WHAT IS KNOWN AND OBJECTIVE: There are acknowledged benefits to continuing metformin when initiating insulin, but there appears to be growing concern over the role of sulphonylureas and thiazolidinediones when used in combination with insulin. This analysis investigates the effects of continuing or discontinuing oral antidiabetic drugs (OADs) following the initiation of once-daily insulin detemir. METHODS: SOLVE is a 24-week, multinational observational study of insulin detemir initiation in patients with type 2 diabetes mellitus treated with one or more OADs. RESULTS: In the total cohort (n = 17 374), there were significant improvements in HbA1c (-1·3%, 95% CI -1·34; -1·27%) and weight (-0·6 kg, 95% CI -0·65; -0·47 kg), with an increase in the incidence rate of minor hypoglycaemia (+0·256 events ppy, P < 0·001), but not severe hypoglycaemia (-0·038 events ppy, P < 0·001). Study participants had information on OAD use either prior to (n = 17 086) or during insulin initiation (n = 16 346). HbA1c reductions were significantly greater in patients continuing treatment with metformin (-1·3% vs. -1·1%, P < 0·01), thiazolidinediones (-1·3% vs. -1·0%, P < 0·01) and DPP-IV inhibitors (-1·3% vs. -0·9%, P < 0·001). Final insulin doses were significantly greater in patients discontinuing treatment with sulphonylureas (0·29 vs. 0·26 IU/kg, P < 0·001), glinides (0·28 vs. 0·26 IU/kg, P < 0·01), thiazolidinediones (0·31 vs. 0·26 IU/kg, P < 0·001) and DPP-IV inhibitors (0·35 vs. 0·29 IU/kg, P < 0·001) compared with patients continuing these respective agents. All patient subgroups had a mean weight loss irrespective of OAD continuation, apart from those continuing thiazolidinediones (+0·2 kg). The largest improvements in weight were seen following the withdrawal of sulphonylureas and thiazolidinediones (-1·1 and -1·1 kg, respectively). WHAT IS NEW AND CONCLUSION: Discontinuation (or switching) of OADs at the time of insulin initiation appears to be governed principally by concerns about hypoglycaemia and weight. HbA1c improvements were smaller in patients discontinuing OADs at the time of insulin initiation and may be associated with insufficient insulin titration.

Resource utilisation and quality of life following initiation of insulin detemir in patients with type 2 diabetes mellitus.

OBJECTIVE: Barriers to insulin initiation in type 2 diabetes mellitus (T2DM) include fear of treatment complexity and perceived lack of time and resources by primary care physicians. The SOLVE study investigated the effect of insulin initiation on resource utilisation and patient quality of life. METHODS: SOLVE was a 24-week cohort study in 10 countries evaluating the safety and effectiveness of initiating once-daily insulin detemir in patients with T2DM. Patient quality of life was assessed using the Insulin Treatment Appraisal Scale (ITAS). RESULTS: A total of 14,611 (84%) patients completed the 24-week study. During the study, HbA1c improved by 1.3 ± 1.5%. The corresponding insulin dose increased from 13 ± 6 IU (0.16 ± 0.09 IU/kg) at baseline, to 22 ± 16 IU (0.27 ± 0.17 IU/kg) at final visit. FlexPen was the preferred device (63%) for insulin administration. The time taken to teach patients to self-inject and perform dose self-adjustment was 15 ± 13 min and 11 ± 11 min, respectively. The quality of life analysis included 6875 patients. The addition of insulin was associated with an improvement in mean ITAS score [-3.5 (95% CI -3.8, -3.3), p < 0.001]. Physicians reported the use or self-adjustment of insulin detemir as easy or very easy in 79% of participants; and satisfaction with the level of glycaemic control was reported for 74% of patients. CONCLUSIONS: Initiating basal insulin therapy resulted in a substantial decrease in HbA1c and improved patients' perceptions of insulin treatment.

The safety and efficacy of adding once-daily insulin detemir to oral hypoglycaemic agents in patients with type 2 diabetes in a clinical practice setting in 10 countries.

AIMS: Evaluate the safety and efficacy of once-daily insulin detemir initiated in routine clinical practice in patients with type 2 diabetes mellitus inadequately controlled with oral hypoglycaemic agents (OHAs). METHODS: This large observational study was conducted in 10 countries. Adverse event data (including hypoglycaemia) and glycaemic control were recorded before and 24 weeks following insulin initiation while patients continued routine clinical management. RESULTS: In this study, 17 374 patients (53% male) were included. Mean pre-insulin values (±s.d.) were: age 62 ± 12 years; body mass index (BMI) 29.3 ± 5.4 kg/m(2); diabetes duration 10 ± 7 years; haemoglobin A1c (HbA1c) 8.9 ± 1.6%. During the study, 27 patients experienced serious adverse drug reaction, severe hypoglycaemic events or both; and there were 31 episodes of severe hypoglycaemia in 21 patients. After 24 weeks, HbA1c was 7.5 ± 1.2% (change of -1.3%; p < 0.001) and mean weight change was -0.6 kg (confidence interval -0.7, -0.5 kg, p < 0.001). Daily insulin dose increased from 13 ± 6 U (0.16 ± 0.09 U/kg) to 22 ± 16 U (0.27 ± 0.17U/kg) by 24 weeks. Multivariate regression analysis identified several independent demographic and treatment predictors of end of study HbA1c. CONCLUSIONS: Addition of once-daily insulin detemir to patients with type 2 diabetes mellitus on OHA therapy resulted in few adverse events, significant improvements in glycaemic control, small reductions in weight and low rates of hypoglycaemia. On the basis of this study, concerns about hypoglycaemia or weight gain should not preclude initiation of basal insulin analogues in patients with poor glycaemic control on OHAs.

Risk factors for respiratory syncytial virus hospitalisation in children with heart disease.

OBJECTIVE: To assess the risk and risk factors for respiratory syncytial virus (RSV) hospitalisation and determinants of the severity of RSV disease in children with heart disease. METHODS: By using a database on RSV tests in Denmark all children with RSV diagnosed with heart disease in Denmark from January 1996 to April 2003 were identified. For each case child one control child matched for age and centre was drawn from the population of children with heart disease. Clinical information was obtained through a review of all records. RESULTS: Data were obtained on 313 pairs. Median age at admission was 280 days (range 15-2379). In the multivariate analysis predictors of RSV hospitalisation were Down syndrome (odds ratio (OR) 3.24, 95% CI 1.80 to 5.80), cardiomyopathy (OR 5.84, 95% CI 1.26 to 27.16) and haemodynamically significant heart disease (OR 1.53, 95% CI 1.04 to 2.26). During RSV hospitalisation predictors of the need for respiratory support (supplemental oxygen, nasal continuous positive airway pressure or mechanical ventilation) were young age (relative risk (RR) 0.47, 95% CI 0.32 to 0.67 per additional year of age) and cardiac decompensation (RR 1.81, 95% CI 1.02 to 3.23). The incidence rate of RSV hospitalisation among children with any heart disease aged 0-23 months was 5.65 per 100 child-years. CONCLUSION: In children with heart disease risk factors for RSV admission are Down syndrome, cardiomyopathy and haemodynamically significant heart disease. Young age and cardiac decompensation are associated with a more severe course of RSV disease.