Reducing Hypoglycemia in T1D and T2D: Insulin Degludec vs Insulin Glargine

According to the results of 2 clinical trials, patients with either type 1 diabetes (T1D) or type 2 diabetes (T2D) had reduced rates of hypoglycemic episodes when treated with insulin degludec vs insulin glargine. Both trial results were recently published in JAMA.^1,2

In SWITCH 1 (A Randomized, Double Blind, Cross-Over Trial Comparing the Safety of Insulin Degludec and Insulin Glargine, Both With Insulin Aspart as Mealtime Insulin in Subjects With Type 1 Diabetes; ClinicalTrials.gov identifier: NCT02034513), 501 patients were randomly assigned to receive either insulin degludec followed by insulin glargine U100 (n=249) or insulin glargine U100 followed by insulin degludec (n=252).¹ Within each treatment sequence, patients were also randomly assigned to either morning or evening dosing.

Patients were treated during 2 treatment periods (between January 2014 and January 2016) for 32 weeks, each with 16-week titration and 16-week maintenance periods.

The rate of overall severe or blood glucose-confirmed symptomatic hypoglycemic episodes during the maintenance period was designated as the primary end point, with nocturnal symptomatic hypoglycemic episodes and the proportion of patients with severe hypoglycemia during the maintenance period as the secondary end points.

In the insulin degludec group, the rates of overall symptomatic hypoglycemia were 2200.9 episodes per 100 person-years’ exposure (PYE) vs 2462.7 episodes per 100 PYE in the insulin glargine U100 group, for a rate ratio (RR) of 0.89 (95% CI, 0.85-0.94; P <.001 for noninferiority; P <.001 for superiority; rate difference, −130.31 episodes per 100 PYE; 95% CI, −193.5 to −67.16 episodes).

Meanwhile, the rates of nocturnal hypoglycemia were 277.1 per 100 PYE in the insulin degludec group vs 428.6 episodes per 100 PYE in the insulin glargine U100 group, for a RR of 0.64 (95% CI, 0.56-0.73; P <.001 for noninferiority; P <.001 for superiority; rate difference, −61.94 episodes per 100 PYE; 95% CI, −83.85 to −40.03 episodes).

A lower proportion of patients in the insulin degludec group experienced severe hypoglycemia compared with patients in the insulin glargine group (10.3% [95% CI, 7.3%-13.3%] vs 17.1% [95% CI, 13.4%-20.8%], respectively; McNemar P =.002; risk difference, −6.8% [95% CI, −10.8% to −2.7%]).

Some of the study’s limitations included the level of patient monitoring in a trial vs clinic setting, the possibility for carryover in the crossover design, and a high rate of patient withdrawal from the trial.

Despite the limitations, the researchers concluded that treatment with insulin degludec resulted in a reduced rate of hypoglycemic episodes compared with insulin glargine U100 in patients with T1D.

In SWITCH 2 (A Randomized, Double Blind, Cross-Over Trial Comparing the Safety and Efficacy of Insulin Degludec and Insulin Glargine, With or Without OADs in Subjects With Type 2 Diabetes; ClinicalTrials.gov identifier: NCT02030600), researchers focused their attention on patients with T2D.²

A total of 721 patients were randomly assigned to receive either insulin degludec followed by insulin glargine U100 (n=361) or insulin glargine U100 followed by insulin degludec (n=360), and similar to SWITCH 1 patients, SWITCH 2 patients were also randomly assigned to either morning or evening dosing in each treatment sequence.

The primary and secondary end points were the same for SWITCH 2 as they were for SWITCH 1.

In the insulin degludec group, the rates of overall symptomatic hypoglycemia were 185.6 episodes per 100 PYE vs 265.4 episodes per 100 PYE in the insulin glargine U100 group, for a RR of 0.70 (95% CI, 0.61-0.80; P <.001; difference, −23.66 episodes per 100 PYE; 95% CI, −33.98 to −13.33 episodes).

Meanwhile, the rates of nocturnal hypoglycemia were 55.2 per 100 PYE in the insulin degludec group vs 93.6 episodes per 100 PYE in the insulin glargine U100 group, for a RR of 0.58 (95% CI, 0.46-0.74; P <.001; difference, −7.41 episodes per 100 PYE; 95% CI, −11.98 to −2.85).

Similar to patients in the SWITCH 1 trial, a lower proportion of patients who received insulin degludec experienced severe hypoglycemia compared with patients who received insulin glargine U100 (1.6% [95% CI, 0.6%-2.7%] vs 2.4% [95% CI, 1.1%-3.7%], respectively; McNemar P =.35; risk difference, −0.8% [95% CI, −2.2% to 0.5%]).

In addition to the limitations faced in SWITCH 1, the researchers of SWITCH 2 noted that once-daily basal insulin may not have been a first-choice treatment for this population in a clinical setting, and handling rescue therapy for patients who were not at target glycemic control who needed bolus insulin was not included in the trial.

“The hypoglycemia findings were consistent when analyzed over the full treatment period, and they showed a statistically significant lower rate of severe hypoglycemia with insulin degludec,” the researchers concluded.

“[I]nsulin degludec and insulin glargine U100 were titrated to the same fasting blood glucose target (71-90 mg/dL) and reached an equivalent, noninferior HbA_1c level.”

Disclosures: Both studies were funded by Novo Nordisk, which was involved in the trial design and protocol development.

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):45-56. doi: 10.1001/jama.2017.7117