Recent zijn in het vooraanstaande medische tijdschrift ‘the Lancet’ twee studies verschenen die insuline degludec, een ultra-langwerkende insuline, hebben onderzocht bij patiënten met diabetes.

Type 2 diabetes
In een open-label studie met een studieduur van 52 weken werden in totaal 1006 patiënten met type 2 diabetes geïncludeerd: 755 patiënten werden behandeld met insuline degludec en 251 patiënten met insuline glargine. In beide groepen vormden deze insulines de basale insuline van een basaal-bolus regime. Het primaire eindpunt van de studie was de verandering in HbA1c, waarbij de onderzoekers alleen wilden weten of insuline degludec niet minder zou zijn dan insuline glargine. Na 1 jaar was het HbA1c 1.1% gedaald in de degludec groep en 1.2% in de glargine groep. Er waren minder hypoglycemieën in de degludec groep (11.1 versus 13.6 per patiëntjaar voor respectievelijk degluded en glargine); er werd geen verschil gevonden in het optreden van ernstige hypoglycemieën.

Type 1 diabetes
De studie bij patiënten met type 1 diabetes was vergelijkbaar opgezet vergeleken met de studie bij type 2 diabetes. In totaal werden er 629 patiënten geïncludeerd: 472 werden behandeld met insuline degludec en 157 patiënten met insuline glargine.
Na 1 jaar was het HbA1c 0.40% gedaald in de degludec groep en 0.39% in de glargine groep. Er werd geen verschil gevonden in de incidentie van hypoglycemieën. Nachtelijke hypoglycemieën werden minder gezien met insuline degludec (4.41 episoden per patiëntjaar versus 5.86 episoden).

Conclusie
In de editorial over beide artikelen werd geconcludeerd dat insuline degludec geen revolutie is, maar gezien moet worden als een evolutie van insulinebehandeling bij patiënten met type 1 en type 2 diabetes.

Bron: Lancet 2012;379(9825):1489-507.


Insulin degludec, an ultra-longacting basal insulin, versus insulin glargine in basal-bolus treatment with mealtime insulin aspart in type 2 diabetes (BEGIN Basal-Bolus Type 2): a phase 3, randomised, open-label, treat-to-target non-inferiority trial.

Garber AJ, King AB, Del Prato S, Sreenan S, Balci MK, Muñoz-Torres M, Rosenstock J, Endahl LA, Francisco AM, Hollander P; NN1250-3582 (BEGIN BB T2D) Trial Investigators.

BACKGROUND:
Basal insulin therapy does not stop loss of β-cell function, which is the hallmark of type 2 diabetes mellitus, and thus diabetes control inevitably deteriorates. Insulin degludec is a new, ultra-longacting basal insulin. We aimed to assess efficacy and safety of insulin degludec compared with insulin glargine in patients with type 2 diabetes mellitus.
METHODS:
In this 52 week, phase 3, open-label, treat-to-target, non-inferiority trial, undertaken at 123 sites in 12 countries, we enrolled adults (aged ≥18 years) with type 2 diabetes mellitus and a glycated haemoglobin (HbA(1c)) of 7•0-10•0% after 3 months or more of any insulin regimen (with or without oral antidiabetic drugs). We randomly allocated eligible participants in a 3:1 ratio to receive once-daily subcutaneous insulin degludec or glargine, stratified by previous insulin regimen, via a central interactive response system. Basal insulin was titrated to a target plasma glucose concentration of 3•9-<5•0 mmol/L self-measured before breakfast. The primary outcome was non-inferiority of degludec to glargine measured by change in HbA(1c) from baseline to week 52 (non-inferiority limit of 0•4%) by ANOVA in the full analysis set. We assessed rates of hypoglycaemia in all treated patients. This study is registered with ClinicalTrials.gov, number NCT00972283.
FINDINGS:
744 (99%) of 755 participants randomly allocated degludec and 248 (99%) of 251 allocated glargine were included in the full analysis set (mean age 58•9 years [SD 9•3], diabetes duration 13•5 years [7•3], HbA(1c) 8•3% [0•8], and fasting plasma glucose 9•2 mmol/L [3•1]); 618 (82%) and 211 (84%) participants completed the trial. After 1 year, HbA(1c) decreased by 1•1% in the degludec group and 1•2% in the glargine group (estimated treatment difference [degludec-glargine] 0•08%, 95% CI -0•05 to 0•21), confirming non-inferiority. Rates of overall confirmed hypoglycaemia (plasma glucose <3•1 mmol/L or severe episodes requiring assistance) were lower with degludec than glargine (11•1 vs 13•6 episodes per patient-year of exposure; estimated rate ratio 0•82, 95% CI 0•69 to 0•99; p=0•0359), as were rates of nocturnal confirmed hypoglycaemia (1•4 vs 1•8 episodes per patient-year of exposure; 0•75, 0•58 to 0•99; p=0•0399). Rates of severe hypoglycaemia seemed similar (0•06 vs 0•05 episodes per patient-year of exposure for degludec and glargine) but were too low for assessment of differences. Rates of other adverse events did not differ between groups.
INTERPRETATION:
A policy of suboptimum diabetes control to reduce the risk of hypoglycaemia and its consequences in advanced type 2 diabetes mellitus might be unwarranted with newer basal insulins such as degludec, which are associated with lower risks of hypoglycaemia than insulin glargine.

Insulin degludec, an ultra-longacting basal insulin, versus insulin glargine in basal-bolus treatment with mealtime insulin aspart in type 1 diabetes (BEGIN Basal-Bolus Type 1): a phase 3, randomised, open-label, treat-to-target non-inferiority trial

Simon Heller, John Buse, Miles Fisher, Satish Garg, Michel Marre, Ludwig Merker, Eric Renard, David Russell-Jones, Areti Philotheou

BACKGROUND
Background Intensive basal-bolus insulin therapy has been shown to improve glycaemic control and reduce the risk of long-term complications that are associated with type 1 diabetes mellitus. Insulin degludec is a new, ultra-longacting basal insulin. We therefore compared the effi cacy and safety of insulin degludec and insulin glargine, both administered once daily with mealtime insulin aspart, in basal-bolus therapy for type 1 diabetes.
METHODS:
In an open-label, treat-to-target, non-inferiority trial, undertaken at 79 sites (hospitals and centres) in six countries, adults (aged ≥18 years) with type 1 diabetes (glycated haemoglobin [HbA1c] ≤10% [86 mmol/mol]), who had been treated with basal-bolus insulin for at least 1 year, were randomly assigned in a 3:1 ratio, with a computergenerated blocked allocation sequence, to insulin degludec or insulin glargine without stratifi cation by use of a central interactive response system. The primary outcome was non-inferiority of degludec to glargine, assessed as a reduction in HbA1c after 52 weeks, with the intention-to-treat analysis. This trial is registered with ClinicalTrials.gov, number NCT00982228.
FINDINGS
Of 629 participants, 472 were randomly assigned to insulin degludec and 157 to insulin glargine; all were analysed in their respective treatment groups. At 1 year, HbA1c had fallen by 0.40% points (SE 0.03) and 0.39% points (0.07), respectively, with insulin degludec and insulin glargine (estimated treatment difference –0.01% points [95% CI –0.14 to 0.11]; p<0.0001 for non-inferiority testing) and 188 (40%) and 67 (43%) participants achieved a target HbA1c of less than 7% (<53 mmol/mol). Rates of overall confirmed hypoglycaemia (plasma glucose <3.1 mmol/L or severe) were similar in the insulin degludec and insulin glargine groups (42.54 vs 40.18 episodes per patient-year of exposure; estimated rate ratio [degludec to glargine] 1.07 [0.89 to 1.28]; p=0.48). The rate of nocturnal confirmed hypoglycaemia was 25% lower with degludec than with glargine (4.41 vs 5.86 episodes per patient-year of exposure; 0.75 [0.59 to 0.96]; p=0.021). Overall serious adverse event rates (14 vs 16 events per 100 patient-years of exposure) were similar for the insulin degludec and insulin glargine groups.
INTERPRETATION
Insulin degludec might be a useful basal insulin for patients with type 1 diabetes because it provides effective glycaemic control while lowering the risk of nocturnal hypoglycaemia, which is a major limitation of insulin therapy.