Glucagon-like peptide-1 (GLP-1): effect on kidney hemodynamics and renin-angiotensin-aldosterone system in healthy men.

INTRODUCTION: Glucagon-like peptide-1 (GLP-1) is an incretin hormone with multiple actions in addition to control of glucose homeostasis. GLP-1 is known to cause natriuresis in humans, but the effects on basic renal physiology are still partly unknown. SUBJECTS AND METHODS: Twelve healthy young males were examined in a randomized, controlled, double-blinded, single-day, crossover trial to evaluate the effects of 2 hours GLP-1 infusion on kidney functions. Glomerular filtration rate (GFR) and renal plasma flow (RPF) were assessed with (51)Cr-EDTA and (123)I-hippuran, respectively, using a constant infusion renal clearance technique based on timed urine sampling. RESULTS: GLP-1 had no significant effect on either GFR [+1.9%, 95% confidence interval (-0.8; 4.6%)] or RPF [+2.4%, 95% confidence interval (-3.6; 8.8%)]. Fractional urine excretion of lithium increased 9% (P = .013) and renal sodium clearance increased 40% (P = .007). Angiotensin II decreased 19% (P = .003), whereas renin, aldosterone, and the urinary excretion of angiotensinogen showed no significant changes. glp-1 did not affect blood pressure but induced a small transient increase in heart rate. CONCLUSION: The results indicate that although GLP-1 markedly reduces proximal tubule sodium reabsorption, the acute effects on GFR and RPF are very limited in healthy humans. The finding of GLP-1's ability to reduce angiotensin II concentration is novel and should be further elucidated.

Targeting postprandial hyperglycaemia in patients with recently diagnosed type 2 diabetes with a fixed, weight-based dose of insulin Aspart.

OBJECTIVE: To assess the effect of substitution of early insulin release with a small weight-based dose of the rapid acting insulin analogue, insulin Aspart (IAsp), on postprandial hyperglycaemia in patients with recently diagnosed type 2 diabetes. MATERIAL AND METHODS: In a randomized, double-blind, double-dummy design, 20 patients underwent three 3-day periods with injection of IAsp 0.06 IU/kg BW or placebo 30 min before main meals. The effect on blood glucose fluctuations was evaluated using a continuous glucose monitoring system. Efficacy endpoints were time with glucose values above 8 mmol/L and glucose area above 8 mmol/L; safety endpoint was time with glucose values below 4 mmol/L in the last 24 h in the treatment periods. RESULTS: IAsp significantly reduced the duration of blood glucose values above 8 mmol/L compared with placebo during 24 h (8.1+/-1.4 h versus 12.7+/-1.3 h), (p<0.03). Glucose areas above 8 mmol/L were 0.6+/-0.2 mmol/lxh and 1.2+/-0.2 mmol/lxh for IAsp and placebo, respectively (p<0.001). Two patients (one in each of the IAsp and placebo periods) had two asymptomatic episodes of glucose registration below 4 mmol/L. Patients with HbA(1c) below 7.4 % obtained the greatest reduction in duration of blood glucose values above 8 mmol/L, whereas the decrease in blood glucose increments for patients with HbA(1c) above 7.4 % was not significantly different from placebo. CONCLUSIONS: A fixed dose of IAsp injected 30 min before mealtimes reduced the postprandial glucose increment in patients with recently diagnosed type 2 diabetes without the risk of hypoglycaemia. Glucose fluctuations in patients with HbA(1c) below 7.4 % improved to near normal level.

Update on Novo Nordisk's clinical trial programme on NovoSeven.

Recombinant coagulation factor VIIa (rFVIIa; Novoseven, Novo Nordisk A/S, Bagsvaerd, Denmark) is registered in most regions of the world for the treatment of bleeding episodes in haemophilia patients with inhibitors to factor VIII or IX. Since its initial availability, there have been several case stories on the investigational use of rFVIIa as a haemostatic agent in a variety of bleeding patients. Novo Nordisk recognizes the need to establish clinical guidance, and when possible, regulatory approvals for indications with bleeding episodes of various aetiologies. Currently, the safety and efficacy of rFVIIa is being investigated in 11 multinational, phase II trials, involving more than 1500 patients. Most of these trials have been designed to establish the efficacy of rFVIIa as a rescue treatment in episodes of severe life-threatening (upper gastrointestinal bleeding, stem cell transplantation, intra-cerebral haemorrhage and trauma). The remaining focus is on the prophylactic use of rFVIIa to improve haemostasis during surgery (orthotopic liver transplantation and liver resection), with the aim of avoiding or reducing the need for blood transfusions. In addition, Novo Nordisk is also continuing studies in haemophilia patients with inhibitors to increase therapeutic knowledge within this indication. Studies addressing dosages and regimens in subpopulations are presently ongoing.

[The roles and responsibilities of the pharmaceutical industry]. / Medicinalfirmaers rolle og ansvar ved laegemiddelforsøg.

A major part of clinical research in Denmark involves clinical testing of pharmaceuticals sponsored by the pharmaceutical industry. All these trials are carried out according to Good Clinical Practice (GCP) and necessitate a close working relationship between responsible investigators and the pharmaceutical industry. It is of mutual interest that these trials should have a high scientific standard and that the integrity of patients always has the highest priority. Many guidelines, laws and conventions regulate this area to ensure the fulfilment of these goals. In the present article, we describe the roles and responsibilities that pharmaceutical companies have to comply with.