Spotlight on insulins degludec and glargine

Multiple recent industry-funded studies compared degludec, an ultralong-acting, once-daily basal insulin, to basal insulin glargine.

Two trials used the same protocol to compare hypoglycemia rates between the insulins in patients with type 1 or type 2 diabetes. Both were crossover trials, randomizing patients to once-daily degludec for 32 weeks, followed by 32 weeks of insulin glargine U100, or the reverse, with additional randomization to morning or evening dosing. The primary endpoint was the rate of severe or blood-glucose confirmed (<56 mg/dL [3.11 mmol/L]) symptomatic hypoglycemic episodes during the latter 16 weeks of taking either insulin. Both studies were published in the July 4 JAMA and funded by Novo Nordisk.

The first trial, SWITCH 1, included 501 adults with type 1 diabetes and at least one hypoglycemia risk factor, 395 of whom completed the trial. The other, SWITCH 2, included 721 adults with type 2 diabetes and at least one hypoglycemia risk factor who were previously treated with basal insulin with or without oral diabetes drugs; 580 of these patients completed the trial. In both trials, rates of overall symptomatic hypoglycemia were lower with insulin degludec than glargine (SWITCH 1: 2,200.9 episodes per 100 patient-years of exposure (PYE) vs. 2,462.7 per 100 PYE; rate ratio [RR], 0.89; SWITCH 2: 185.6 per 100 PYE vs. 265.4 per 100 PYE; RR, 0.70). Rates of nocturnal symptomatic hypoglycemia were also significantly lower with insulin degludec in both trials. The proportions of patients experiencing severe hypoglycemia were also lower with degludec than glargine (SWITCH 1: 10.3% vs. 17.1%; SWITCH 2: 1.6% vs. 2.4%).

Both trials showed that in patients like those studied, taking insulin degludec resulted in a reduced rate of overall symptomatic hypoglycemia, the authors concluded. They noted several limitations, including that the monitoring of patients for hypoglycemia may have been more intense than in real-world settings, that more patients than expected withdrew, and that in SWITCH 2, the first choice of treatment for the patients might not have been once-daily basal insulin.

An accompanying editorial added caveats for physicians considering recommending degludec over insulin glargine, including the industry funding of the trials, affordability concerns, practicality of the set insulin titration protocols for common clinical practice, and uncertain generalizability of the findings to insulin glargine U300 or other alternative basal insulins.

Another study, published online in the New England Journal of Medicine on June 12, was also funded by Novo Nordisk and compared the two insulins on severe hypoglycemia, but had as its primary outcome the first occurrence of a major cardiovascular event (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke). It included 7,637 patients with type 2 diabetes, 6,509 of whom had established cardiovascular disease, chronic kidney disease, or both.

Patients were randomized to insulin degludec or glargine U100 once daily between dinner and bedtime for about two years. There was no significant difference between groups in the primary outcome (8.5% of patients on degludec vs. 9.3% on glargine). Mean HbA1cs were also similar, but the mean fasting plasma glucose was lower in the degludec group (128 mg/dL vs. 136 mg/dL). Severe hypoglycemia occurred in significantly fewer patients taking degludec than glargine (4.9% vs. 6.6%; RR, 0.60; P<0.001).

The study authors concluded that insulin degludec was noninferior to insulin glargine with respect to incidence of major cardiovascular events in these patients. The primary limitation of the study was its duration (two years) and it is uncertain whether the results can be extrapolated to longer exposure or patients with lower risk of cardiovascular events, the authors said.