Anne Louise Svendsen

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

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).

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

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).

Meta-analysis of insulin aspart versus regular human insulin used in a basal–bolus regimen for the treatment of diabetes mellitus

The objective of the current study was to compare the efficacy of two different insulin formulations, insulin aspart (IAsp) and regular human insulin (RHI), for prandial insulin coverage with neutral protamine Hagedorn (NPH) insulin as basal insulin using a meta‐analysis approach. The primary endpoint was change in A1c over time. Secondary endpoints included incidence of hypoglycemia and postprandial glycemic control.

Effect of Baseline Glycosylated Hemoglobin A1c on Glycemic Control and Diabetes Management Following Initiation of Once-Daily Insulin Detemir in Real-Life Clinical Practice

OBJECTIVE The SOLVE study investigated the initiation of basal insulin in patients with type 2 diabetes on oral antidiabetic (OAD) treatment and outcomes in patients with varying levels of glycemic control at baseline. METHODS This was an observational cohort study conducted in 10 countries using insulin detemir. Data were collected at 3 clinic visits (baseline, 12-week interim, and 24-week final visit). RESULTS A total of 13,526 (77.9%) patients were included in the glycosylated hemoglobin A1c (HbA1c) subset analysis. Patients were grouped according to pre-insulin HbA1c values as follows: HbA1c <7.6% (n = 2,797); HbA1c 7.6-9% (n = 5,366), and HbA1c >9% (n = 5,363). A total of 27 patients experienced serious adverse drug reactions (SADRs) and/or severe hypoglycemia (3, 10, and 11 patients with pre-insulin HbA1c <7.6%, 7.6-9.0%, and >9.0%, respectively). All patient subgroups realized improvements in HbA1c, with the pre-insulin HbA1c >9% subgroup having the largest HbA1c reduction (-2.4% versus -0.9% and -0.2% for HbA1c subgroups 7.6-9% and <7.6%, respectively). In the total cohort (n = 17,374), the incidence of severe hypoglycemia decreased from 4 events per 100 person years to <1 event per 100 person years by final visit; the incidence of minor hypoglycemia increased from 1.6 to 1.8 events per person year. CONCLUSIONS In this study, insulin initiation was delayed until late in disease course, and overall concordance with internationally recognized guidelines was low. The initiation of once-daily insulin detemir was associated with substantial improvements in glycemic control and was not associated with an increase in severe hypoglycemia or weight gain.

The influence of pharmaceutically induced weight changes on estimates of renal function: A patient-level pooled analysis of seven randomised controlled trials of glucose lowering medication

BACKGROUND Estimation of kidney function (eGFR) is essential in monitoring of patients with kidney disease. Estimates of kidney function based on serum creatinine are derived from cross-sectional studies. If body weight (BW) changes, this might affect creatinine and eGFR. The Cockcroft-Gault (CG) equation includes creatinine and BW, whereas the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations only include creatinine. METHODS Data were pooled from the six LEAD (Liraglutide Effect and Action in Diabetes) trials and the LIRA-DPP4 trial. The trials were conducted in patients with type 2 diabetes and of 26weeks duration. We investigated changes in eGFR for patients treated with liraglutide, and for patients treated with glucose-lowering medications with less weight-reducing effects (insulin glargine, glimepiride, exenatide and rosiglitazone). RESULTS We included 5100 patients (liraglutide n=3173, comparator n=1927). Mean (SD) CKD-EPI eGFR was 81.2 (20.6) ml/min/1.73m(2) for liraglutide and 81.6 (20.3) ml/min/1.73m(2) for comparator. For liraglutide, BW changed -1.9 (95% CI (-2.0; -1.8)) kg, for comparator BW changed 0.2 (95% CI (0.03; 0.3)) kg. Using regression modelling, a 10% BW decrease yielded no change in creatinine, MDRD eGFR or CKD-EPI eGFR for both liraglutide and comparator, but was associated with a 10.2% (-11.3%; -9.1%) decrease in CG eGFR for liraglutide, and a 10.6% (-12.0%; -9.1%) decrease for comparator. CONCLUSIONS A liraglutide-induced weight reduction of 1.9kg was not associated with change in creatinine. Accordingly, there was no change in weight-independent estimates of GFR, whereas weight-dependent estimates were changed. The MDRD and CKD-EPI equations can be used in patients experiencing pharmaceutically induced weight reductions.

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

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.

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

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.

Initiation of once daily insulin detemir is not associated with weight gain in patients with type 2 diabetes mellitus: results from an observational study

BackgroundObesity is common in type 2 diabetes (T2DM) and is associated with increased risk of morbidity and all-cause mortality. This analysis describes weight changes associated with insulin detemir initiation in real-life clinical practice.MethodsStudy of Once-Daily Levemir (SOLVE) was a 24-week international observational study of once-daily insulin detemir as add-on therapy in patients with T2DM receiving oral hypoglycaemic agents (OHAs).Results17,374 participants were included in the analysis: mean age 62 ± 12 years; weight 80.8 ± 17.6 kg; body mass index (BMI) 29.2 ± 5.3 kg/m2; diabetes duration 10 ± 7 years; HbA1c 8.9 ± 1.6%. HbA1c decreased by 1.3 ± 1.5% during the study, with insulin doses of 0.27 ± 0.17 IU/kg. Patients with higher BMI had higher pre-insulin HbA1c, and similar reductions in HbA1c with insulin therapy. Weight decreased from 80.8 ± 17.6 kg to 80.3 ± 17.0 kg (change of -0.6 [95% CI -0.65; -0.47] kg), with 35% of patients losing >1 kg. Patients with the highest pre-insulin BMI lost the greatest amount of weight: BMI < 25: +0.8 [95% CI: 0.6; 0.9] kg, 25 ≤ BMI < 30: -0.2 [95% CI: -0.3; -0.8] kg, 30 ≤ BMI < 35: -1.0 [95% CI: -1.1; -0.8] kg; BMI ≥ 35: -1.9 [95% CI: -2.2; -1.6] kg. Minor hypoglycaemia decreased with increasing BMI: 2.3 and 1.3 events per patient year for BMI <25 and  ≥ 35, respectively.ConclusionsOverall, patients with poorly controlled T2DM achieved significant reductions in HbA1c after initiation of once-daily insulin detemir therapy, without weight gain. The favourable impact of insulin detemir on weight may not apply to other insulin preparations.Trial registrationsClinicalTrials.gov, NCT00825643 and NCT00740519

Safety of once-daily insulin detemir in patients with type 2 diabetes treated with oral hypoglycemic agents in routine clinical practice.

The aim of the present study was to identify demographic and treatment factors that were predictive of hypoglycemia in a large cohort of type 2 diabetic patients initiating insulin detemir.

Safety of once‐daily insulin detemir in patients with type 2 diabetes treated with oral hypoglycemic agents in routine clinical practice (在常规临床实践中使用口服降糖药治疗的2型糖尿病患者每日一次使用地特胰岛素治疗的安全性)

The aim of the present study was to identify demographic and treatment factors that were predictive of hypoglycemia in a large cohort of type 2 diabetic patients initiating insulin detemir.