SWITCH Trials Find Less Hypoglycemia Among Those Using Tresiba

The trials appearing in JAMA found insulin degludec showed even stronger benefits in helping avoid hypoglycemia at night, which is always a concern for those with diabetes.

Patients with diabetes at risk for hypoglycemia were less likely to have an episode while using insulin degludec compared with insulin glargine U100, according to a pair of trials reported this week in JAMA.

The SWITCH trials, which examined those with type 1 (T1D) and type 2 diabetes (T2D), found that insulin degludec, sold by Novo Nordisk as Tresiba, resulted in a reduced rate of hypoglycemic episodes among those with at least 1 risk factor for hypoglycemia.

SWITCH 1 involved 501 patients1 with T1D while SWITCH 2 involved 721 patients2 with T2D. Both trials used the same design: patients were randomized to use either insulin degludec or insulin glargine U100 for 32 weeks (16 weeks titration, followed by 16 weeks of maintenance). Then, patients crossed over to take the other insulin, repeating the schedule of 16 weeks’ titration and 16 weeks of maintenance.

As described in an accompanying editorial, both insulins are the basal component of an insulin regimen, but insulin degludec has a longer half-life—25.4 hours compared with 12.1 hours for insulin glargine U100.3

SWITCH 1. Of the 501 patients (mean age, 45.9 years; 53.7% men), 79% completed the trial. Researchers found lower rates of overall symptomatic hypoglycemic episodes and especially nocturnal symptomatic hypoglycemia for those using insulin degludec during the 16-week maintenance period, with a lower share experiencing severe hypoglycemia during the maintenance period (10% vs 17%).

SWITCH 2. Of the 721 patients (mean age, 61.4 years; mean duration of diabetes, 10.5 years; 53.1% male), 80% completed the trial. Researchers found statistically significant reductions in the rates of hypoglycemia and nocturnal hypoglycemia with insulin degludec compared with insulin glargine U100. The proportions of patients with hypoglycemic episodes were 22.5% for insulin degludec vs 31.6% for insulin glargine U100, and the proportions of patients with nocturnal hypoglycemic episodes were 9.7% vs 14.7%, respectively. Proportions of patients experiencing severe hypoglycemia were 1.6% for insulin degludec versus 2.4% for insulin glargine U100.

A limitation of both studies was the large share of patients who failed to complete the study, which researchers attributed to its length and the demands of switching insulin midway through.

Reducing hypoglycemia risk has become a greater priority in diabetes care; as the editorial that accompanies the studies notes, it is believed to be responsible for 10% of the deaths of those under 40 with T1D. As patients live longer with diabetes, avoiding hypoglycemia becomes more challenging because symptoms disappear with disease duration.

As a result, meetings with FDA over the past year have focused on putting more weight on the importance of reducing hypoglycemia in the approval process for medications and devices.

References

1. Lane W, Bailey TS, Gerety G, et al. Effect of insulin degludec vs insulin glargine U100 on hypoglycemia in patients with type 1 diabetes: the SWITCH 1 randomized clinical trial. JAMA. 2017;318(1):33-44. doi:10.1001/jama.2017.7115.

2. Wysham C, Bhargava A, Chaykin L, et al. Effect of insulin degludec vs insulin glargine U100 on hypoglycemia in patients with type 2 diabetes: the SWITCH 2 randomized clinical trial. JAMA. 2017; 318(1):45-46. doi:10.1001/jama.2017.711.

3. Seaquest ER, Chow LS. Hypoglycemia in diabetes: does insulin type matter? JAMA. 2017;318(1):31-32. doi:10.1001/jama.2017.8075.