Janusz Gumprecht

Initiating insulin therapy with, or switching existing insulin therapy to, biphasic insulin aspart 30/70 (NovoMix® 30) in routine care: safety and effectiveness in patients with type 2 diabetes in the IMPROVE™ observational study

Aims:  The IMPROVE™ observational study evaluated the safety profile and effectiveness of biphasic insulin aspart 30/70 (BIAsp 30) in patients with type 2 diabetes in routine practice in 11 countries.

The IMPROVE™ study – a multinational, observational study in type 2 diabetes: baseline characteristics from eight national cohorts

Aims:  The IMPROVE™ study is a multinational, open‐label, non‐randomised, 26‐week observational study assessing the safety and effectiveness of biphasic insulin aspart 30 (BIAsp 30) treatment in type 2 diabetes in routine clinical practice. The principal aims of this report were to characterise the baseline population and physicians’ treatment decisions.

The use of statins in people at risk of developing diabetes mellitus: Evidence and guidance for clinical practice

Reducing low-density lipoprotein cholesterol (LDL-C) levels using statins is associated with significant reductions in cardiovascular (CV) events in a wide range of patient populations. Although statins are generally considered to be safe, recent studies suggest they are associated with an increased risk of developing Type 2 diabetes (T2D). This led the US Food and Drug Administration (FDA) to change their labelling requirements for statins to include a warning about the possibility of increased blood sugar and HbA1c levels and the European Medicines Agency (EMA) to issue guidance on a small increased risk of T2D with the statin class. This review examines the evidence leading to these claims and provides practical guidance for primary care physicians on the use of statins in people with or at risk of developing T2D. Overall, evidence suggests that the benefits of statins for the reduction of CV risk far outweigh the risk of developing T2D, especially in individuals with higher CV risk. To reduce the risk of developing T2D, physicians should assess all patients for T2D risk prior to starting statin therapy, educate patients about their risks, and encourage risk-reduction through lifestyle changes. Whether some statins are more diabetogenic than others requires further study. Statin-treated patients at high risk of developing T2D should regularly be monitored for changes in blood glucose or HbA1c levels, and the risk of conversion from pre-diabetes to T2D should be reduced by intensifying lifestyle changes. Should a patient develop T2D during statin treatment, physicians should continue with statin therapy and manage T2D in accordance with relevant national guidelines.

Comparative long-term efficacy and tolerability of pitavastatin 4 mg and atorvastatin 20–40 mg in patients with type 2 diabetes mellitus and combined (mixed) dyslipidaemia

Aim: To compare the long‐term efficacy and safety of pitavastatin with atorvastatin in patients with type 2 diabetes and combined (mixed) dyslipidaemia.

Effect of Insulin Degludec vs Insulin Glargine U100 on Hypoglycemia in Patients With Type 1 Diabetes: The SWITCH 1 Randomized Clinical Trial.

Importance Hypoglycemia, common in patients with type 1 diabetes, is a major barrier to achieving good glycemic control. Severe hypoglycemia can lead to coma or death. Objective To determine whether insulin degludec is noninferior or superior to insulin glargine U100 in reducing the rate of symptomatic hypoglycemic episodes. Design, Setting, and Participants Double-blind, randomized, crossover noninferiority trial involving 501 adults with at least 1 hypoglycemia risk factor treated at 84 US and 6 Polish centers (January 2014-January 12, 2016) for two 32-week treatment periods, each with a 16-week titration and a 16-week maintenance period. Interventions Patients were randomized 1:1 to receive once-daily insulin degludec followed by insulin glargine U100 (n = 249) or to receive insulin glargine U100 followed by insulin degludec (n = 252) and randomized 1:1 to morning or evening dosing within each treatment sequence. Main Outcomes and Measures The primary end point was the rate of overall severe or blood glucose-confirmed (<56 mg/dL) symptomatic hypoglycemic episodes during the maintenance period. Secondary end points included the rate of nocturnal symptomatic hypoglycemic episodes and proportion of patients with severe hypoglycemia during the maintenance period. The noninferiority criterion for the primary end point and for the secondary end point of nocturnal hypoglycemia was defined as an upper limit of the 2-sided 95% CI for a rate ratio of 1.10 or lower; if noninferiority was established, 2-sided statistical testing for superiority was conducted. Results Of the 501 patients randomized (mean age, 45.9 years; 53.7% men), 395 (78.8%) completed the trial. During the maintenance period, the rates of overall symptomatic hypoglycemia were 2200.9 episodes per 100 person-years’ exposure (PYE) in the insulin degludec group vs 2462.7 episodes per 100 PYE in the insulin glargine U100 group for a rate ratio (RR) of 0.89 (95% CI, 0.85-0.94; P < .001 for noninferiority; P < .001 for superiority; rate difference, −130.31 episodes per 100 PYE; 95% CI, −193.5 to −67.16). The rates of nocturnal symptomatic hypoglycemia were 277.1 per 100 PYE in the insulin degludec group vs 428.6 episodes per 100 PYE in the insulin glargine U100 group, for an RR of 0.64 (95% CI, 0.56-0.73; P < .001 for noninferiority; P < .001 for superiority; rate difference, −61.94 episodes per 100 PYE; 95% CI, −83.85 to −40.03). A lower proportion of patients in the insulin degludec than in the insulin glargine U100 group experienced severe hypoglycemia during the maintenance period (10.3%, 95% CI, 7.3%-13.3% vs 17.1%, 95% CI, 13.4%-20.8%, respectively; McNemar P = .002; risk difference, −6.8%; 95% CI, −10.8% to −2.7%). Conclusions and Relevance Among patients with type 1 diabetes and at least 1 risk factor for hypoglycemia, 32 weeks’ treatment with insulin degludec vs insulin glargine U100 resulted in a reduced rate of overall symptomatic hypoglycemic episodes. Trial Registration clinicaltrials.gov Identifier: NCT02034513

Intensification to biphasic insulin aspart 30/70 (BIAsp 30, NovoMix 30) can improve glycaemic control in patients treated with basal insulins: a subgroup analysis of the IMPROVE observational study.

Aims:  The international IMPROVE™ observational study investigated the safety profile and effectiveness of biphasic insulin aspart 30/70 (BIAsp 30) in the routine treatment of patients with type 2 diabetes. We present analyses for the subgroup of patients who switched from basal insulin to BIAsp 30.

Safety and effectiveness of biphasic insulin aspart 30/70 (NovoMix® 30) when switching from human premix insulin in patients with type 2 diabetes : subgroup analysis from the 6-month IMPROVE™ observational study

Aims:  IMPROVE™ is an open‐label, multinational, non‐randomised, 26‐week observational study designed to evaluate the safety and effectiveness of biphasic insulin aspart 30 (BIAsp 30) in routine clinical practice. Here, we report data for patients switching to BIAsp 30 from human premixed insulin.

A Standardized Vascular Disease Health Check in Europe: A Cost-Effectiveness Analysis

Background No clinical trials have assessed the effects or cost-effectiveness of health check strategies to detect and manage vascular disease. We used a mathematical model to estimate the cost-effectiveness of several health check strategies in six European countries. Methods We used country-specific data from Denmark, France, Germany, Italy, Poland, and the United Kingdom to generate simulated populations of individuals aged 40–75 eligible for health checks in those countries (e.g. individuals without a previous diagnosis of diabetes, myocardial infarction, stroke, or serious chronic kidney disease). For each country, we used the Archimedes model to compare seven health check strategies consisting of assessments for diabetes, hypertension, lipids, and smoking. For patients diagnosed with vascular disease, treatment was simulated in a standard manner. We calculated the effects of each strategy on the incidence of type 2 diabetes, major adverse cardiovascular events (MACE), and microvascular complications in addition to quality of life, costs, and cost per quality-adjusted life-year (QALY). Results Compared with current care, health checks reduced the incidence of MACE (6–17 events prevented per 1000 people screened) and diabetes related microvasular complications (5–11 events prevented per 1000 people screened), and increased QALYs (31–59 discounted QALYs) over 30 years, in all countries. The cost per QALY of offering a health check to all individuals in the study cohort ranged from €14903 (France) to cost saving (Poland). Pre-screening the population and offering health checks only to higher risk individuals lowered the cost per QALY. Pre-screening on the basis of obesity had a cost per QALY of €10200 (France) or less, and pre-screening with a non-invasive risk score was similar. Conclusions A vascular disease health check would likely be cost effective at 30 years in Denmark, France, Germany, Italy, Poland, and the United Kingdom.

Polymorphic Genes for Kinin Receptors, Nephropathy and Blood Pressure in Type 2 Diabetic Patients

Background/Aims: There is evidence that hereditary predisposition contributes to the development of diabetic nephropathy and hypertension. Polymorphisms in the genes for bradykinin receptors (B1R and B2R) were found to be associated with decreased risk of the development of end-stage renal disease. This study examines whether B1R G–699C and B2R C181T polymorphisms are associated with microalbuminuria or overt nephropathy, or blood pressure variation in type 2 diabetic subjects. Methods: B1R and B2R polymorphisms were determined in 153 type 2 diabetic patients with microalbuminuria, 132 with overt nephropathy (macroalbuminuria or chronic renal failure), and 161 patients with normoalbuminuria despite diabetes duration longer than 10 years. Results: Distributions of the examined polymorphisms did not differ between patients with microalbuminuria or overt nephropathy, compared to normoalbuminuric control subjects. Patients carrying the B2R T allele had lower DBP, compared with non-carriers: 83.6 ± 12.0 vs. 87.4 ± 12.1 mm Hg, p < 0.05. Among patients not receiving ACEI, both SBP and DBP was significantly lower in B2R T allele carriers, compared to non-carriers (137.2 ± 20.3 vs. 146.5 ± 21.7 mm Hg, and 80.3 ± 11.9 vs. 85.8 ± 11.6 mm Hg, p < 0.05). Conclusions: Examined polymorphisms are not associated with the increased risk of incipient or overt nephropathy in type 2 diabetic patients. B2R C181T polymorphism may contribute to blood pressure variation in these subjects.

Improved glycaemic control with BIAsp 30 in insulin-naïve type 2 diabetes patients inadequately controlled on oral antidiabetics: subgroup analysis from the IMPROVE study

Abstract Objective: The aim of this subanalysis of the IMPROVE study was to evaluate the safety and effectiveness of initiating biphasic insulin aspart 30/70 (BIAsp 30) in type 2 diabetes patients uncontrolled on oral antidiabetic drugs (OADs). Methods: IMPROVE is a 26-week, open-label, non-randomised, international observational study in type 2 diabetes patients prescribed BIAsp 30 in routine clinical practice. The total cohort comprised 52 419 patients from various pre-study therapies. Here results from the subgroup of previously insulin-naïve patients are reported. Changes in glycated haemoglobin (HbA1c), fasting blood glucose (FBG), postprandial blood glucose (PPBG), weight, dose, proportion of patients achieving HbA1c < 7.0%, and rates of major and minor hypoglycaemic events were recorded. Treatment satisfaction was assessed using a validated questionnaire. Results: A total of 29 160 insulin-naïve patients were included; mean age 55.6 years, diabetes duration 7.3 years, baseline HbA1c 9.24%. Significant reductions were seen for HbA1c (−2.12%; p < 0.0001), FBG (−4.07 mmol/L; p < 0.0001) and PPBG after all meals (mean: −5.27 mmol/L; p < 0.0001); 39.2% of patients achieved HbA1c < 7.0% without hypoglycaemia. Better glycaemic control was seen in patients treated with BIAsp 30 twice-daily (BID) both at baseline and final visit, or BID at baseline and three-times daily at final visit, compared with other regimens. The rate of major hypoglycaemic events decreased significantly, while the rate of minor hypoglycaemic events increased. Better glycaemic control and a lower rate of minor hypoglycaemia were observed in patients using BIAsp 30 without OADs than with OADs. There was no clinically relevant change in weight (−0.07 kg; p < 0.0001). At final visit, 59.7% of patients were extremely/very satisfied with treatment, compared with 10.2% at baseline. Conclusions: This open-label, non-randomised, observational study demonstrated that initiating insulin therapy with BIAsp 30 significantly improved glycaemic control in insulin-naïve patients previously poorly controlled on OADs. The rate of major hypoglycaemia was reduced and treatment satisfaction increased after initiation of BIAsp 30. Furthermore, better glycaemic control was achieved with BIAsp 30 without OAD compared to with OAD.