Phase III SWITCH 2 trial of insulin degludec (Tresiba) in type 2 diabetes meets primary endpoint- Novo Nordisk

Novo Nordisk has announced the headline results from SWITCH 2, the first of two 2x32-weeks randomised, double-blind, cross-over, treat-to-target Phase IIIb trials, comparing the safety and efficacy of insulin degludec (Tresiba) and insulin glargine in people with type 2 diabetes. In the trial, 721 people were randomised to cross-over treatment with insulin degludec and insulin glargine, in combination with metformin. The timing of the daily injections of both insulin degludec and insulin glargine was randomised equally to take place either in the morning or evening. The primary end-point of the trial was the number of treatment emergent severe or blood glucose confirmed symptomatic hypoglycaemia episodes during the maintenance period (ie after 16 weeks of treatment).

From a mean baseline of 7.6%, the trial showed non-inferiority in HbA1c reduction of insulin degludec compared to insulin glargine, thus fulfilling the requirements for objectively comparing hypoglycaemia rates between the two treatments. Likewise, the end-of-trial insulin doses were similar at the end of treatment in the two treatment periods. The observed rate of severe or blood glucose confirmed symptomatic hypoglycemia was 186 events per 100 patient years exposed to insulin degludec and 265 events per 100 patient years exposed to insulin glargine during the maintenance period. This reduction was statistically significant, and the trial thus met its primary endpoint by demonstrating a reduction of 30% when people were treated with insulin degludec compared to insulin glargine. The observed rate of severe or blood glucose symptomatic nocturnal confirmed hypoglycaemia in the maintenance period was 55 events per 100 patient years exposed to insulin degludec and 94 events per 100 patient years exposed to insulin glargine, corresponding to a 42% reduction with insulin degludec compared to insulin glargine and showing statistical significance on this confirmatory secondary end-point.

The confirmatory secondary endpoint of proportions of subjects experiencing severe hypoglycaemia during the maintenance period did not reach statistical significance. However, the supportive end-point, rate of severe hypoglycaemia, showed a 46% reduction with insulin degludec in the maintenance period and a statistical significant reduction of 51% with insulin degludec in the full treatment period. In the trial, insulin degludec appeared to have a safe and well-tolerated profile.

Comment: Tresiba has now launched in the USA, where it was intended to compete with Lantus (insulin glargine), the diabetes best-seller from Sanofi. Insulin degludec has advantages over insulin glargine as it has a longer half life and less hypoglycaemia - insulin degludec has a 'flat and steady' dosage profile that allows patients to dose at any time of day. In the meantime Sanofi has gained US approval for Toujeo (basal insulin) a longer-acting successor to Lantus.