NEW YORK – Three new insulins hold the potential for decreasing the risk of severe hypoglycemia episodes in patients with diabetes, Dr. Elizabeth R. Seaquist said at the annual advanced postgraduate course held by the American Diabetes Association.
None of the products are yet available in the the United States, although one of the insulins was approved in February by the Food and Drug Administration and is expected to be on the market later this year. The new insulin glargine (Toujeo; Sanofi), a once-daily long-acting basal insulin, received its FDA approval on Feb. 25.
Toujeo has a flatter glycemic profile and a longer duration of action than does its predecessor insulin glargine, Lantus, said Dr. Seaquist, professor of medicine and the Pennock Family Chair in Diabetes Research at the University of Minnesota, Minneapolis.
Dr. Elizabeth R. Seaquist
The approval of Toujeo was based on results from the EDITION clinical trial series, which included more than 3,500 adults with type 1 or type 2 diabetes. In those studies, once-daily Toujeo was compared with once-daily insulin Lantus in open-label, randomized, active-control, parallel, treat-to-target studies of up to 26 weeks of duration with 6 months’ safety extension, according to a Sanofi press release.
Insulin degludec, a once-daily, long-acting basal insulin analogue, is available in the European Union as Tresiba (Novo Nordisk) at strengths of 100 U/mL and 200 U/mL. The FDA denied its approval in 2013, after a review committee expressed concern about a potential increased risk of major cardiovascular events. The FDA has requested that additional cardiovascular data from a dedicated cardiovascular outcomes trial be provided before considering approval.
Basal insulin peglispro (Lilly) has successfully completed all its phase III studies and is on track for FDA submission this year. The primary efficacy endpoint of noninferior HbA1c, compared with insulin glargine was met in both the IMAGINE-1 and IMAGINE-3 trials, and significantly more patients taking basal insulin peglispro achieved an HbA1c of less than 7%. Further, patients taking basal insulin peglispro experienced weight loss and patients taking insulin glargine experienced weight gain, according to Lilly press releases.
Both trials – in which patients were taking mealtime and basal insulin – also found a significantly lower rate of nocturnal hypoglycemia with basal insulin peglispro. Because of a higher rate of daytime hypoglycemic events, however, there was a statistically significant increase in the rate of total hypoglycemia for patients taking basal insulin peglispro.
In the open-label IMAGINE-1 trial, patients taking basal insulin peglispro reported a statistically significant higher rate of severe hypoglycemic events. However, in the larger, blinded IMAGINE-3 trial the rate of severe hypoglycemic events for treatment with basal insulin peglispro was numerically lower, but the difference was not statistically significant.
The fear of hypoglycemia can prompt patients to be nonadherent with their insulin regimen, Dr. Seaquist said. “And we all know that many patients don’t reach their glycemic goal, so they need additional medications that then put them at an increased risk of hypoglycemia.”
According to one review article, an intensively treated individual with type 1 diabetes can experience up to 10 episodes of symptomatic hypoglycemia per week and severe temporarily disabling hypoglycemia at least once a year. Hypoglycemia is also relatively common in type 2 diabetes, with prevalence rates of 70%-80% in clinical trials using insulin to achieve good metabolic control.
Dr. Seaquist disclosed that she is a consultant for Sanofi Aventis, the maker of Toujeo.