The effect of insulin degludec on risk of symptomatic nocturnal hypoglycaemia in adults with type 1 diabetes and high risk of nocturnal severe hypoglycaemia (the HypoDeg trial): study rationale and design

Rikke Mette Agesen, Amra Ciric Alibegovic, Henrik Ullits Andersen, Henning Beck-Nielsen, Peter Gustenhoff, Troels Krarup Hansen, Christoffer Hedetoft, Tonny Jensen, Claus Bogh Juhl, Susanne Søgaard Lerche, Kirsten Nørgaard, Hans-Henrik Parving, Lise Tarnow, Birger Thorsteinsson, Ulrik Pedersen-Bjergaard, Rikke Mette Agesen, Amra Ciric Alibegovic, Henrik Ullits Andersen, Henning Beck-Nielsen, Peter Gustenhoff, Troels Krarup Hansen, Christoffer Hedetoft, Tonny Jensen, Claus Bogh Juhl, Susanne Søgaard Lerche, Kirsten Nørgaard, Hans-Henrik Parving, Lise Tarnow, Birger Thorsteinsson, Ulrik Pedersen-Bjergaard

Abstract

Background: Hypoglycaemia, especially nocturnal, remains the main limiting factor of achieving good glycaemic control in type 1 diabetes. The effect of first generation long-acting insulin analogues in reducing nocturnal hypoglycaemia is well documented in patient with type 1 diabetes. The effect of the newer long-acting insulin degludec on risk of nocturnal hypoglycaemia remains undocumented in patients with type 1 diabetes and recurrent severe nocturnal hypoglycaemia. The HypoDeg trial is designed to investigate whether insulin degludec in comparison with insulin glargine U100 is superior in limiting the occurrence of nocturnal hypoglycaemia in patients with recurrent nocturnal severe hypoglycaemia. This paper reports the study design of the HypoDeg trial.

Methods/design: A Danish investigator-initiated, prospective, randomised, open, blinded endpoint (PROBE), multicentre, two-year cross-over study investigating the effect of insulin degludec versus insulin glargine U100 on frequency of nocturnal hypoglycaemia in patients with type 1 diabetes and one or more episodes of nocturnal severe hypoglycaemia during the preceding two years as the major inclusion criteria. Patients are randomised (1:1) to basal therapy with insulin degludec or insulin glargine. Insulin aspart is used as bolus therapy in both treatment arms.

Discussion: In contrast to most other insulin studies the HypoDeg trial includes only patients at high risk of hypoglycaemia. The HypoDeg trial will compare treatment with insulin degludec to insulin glargine U100 in terms of risk of nocturnal hypoglycaemic episodes in patients with type 1 diabetes with the greatest potential to benefit from near-physiological insulin replacement therapy. www.clinicaltrials.gov : NCT02192450.

Keywords: Insulin degludec; Insulin glargine; Nocturnal hypoglycaemia; RCT; Severe hypoglycaemia; Type 1 diabetes.

Conflict of interest statement

RMA, ACA, HBN, TKH, CH, TJ, CBJ, SSL, HHP, LT and BT have no competing financial interests. HUA owns stocks in Novo Nordisk. HUA is on advisory boards for Novo Nordisk, Abbott and Astra Zeneca and has received a lecture fee from Nordic Infucare. PG has served on advisory boards for Astra Zeneca, Sanofi Aventis, Novo Nordisk, Boehringer Ingelheim and Abbott Laboratories. KN serves as advisor to Medtronic, Abbott and Novo Nordisk. KN has received fees for speaking from Medtronic, Roche Diabetes Care, Rubin Medical, Sanofi, Novo Nordisk, Zealand Pharma and Bayer. UPB has served on advisory boards for AstraZeneca/Bristol Myers Squibb and Novo Nordisk and has received lecture fee from Astra Seneca/Bristol Myers Squibb, Sanofi Aventis and Novo Nordisk. The authors declare no other conflict of interest.

Figures

Fig. 1
Fig. 1
Study design. Endpoint assessment periods. Admission for overnight plasma glucose monitoring and/or 6 days of ambulatory 24 h continuous glucose monitoring
Fig. 2
Fig. 2
Definition of night. a: night is defined as time from 4 h after evening bolus of short acting insulin until time for actual morning bolus insulin administration. In the example shown the night is from 00:30 until 06:30, b: conventional definition of night from 23:00 to 06:59, c: conventional definition of night from 00:00 to 05:59

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Source: PubMed

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