No Hypoglycemia With At the time-Weekly Insulin? Concerns Stay
The investigational the moment-weekly basal insulin icodec (Novo Nordisk) did not lead to greater hypoglycemia as opposed with the moment-every day insulin glargine U100 in patients with style 2 diabetes, even with intentionally doubled and tripled doses of equally the brokers, new investigate finds.
Insulin icodec will work by reversibly binding to albumin, thereby slowing the release of the lively insulin analogue. It has a 50 percent-daily life of about 1 week, with nearly even distribution of the glucose-decreasing impact about the system of that 7 days. Some have named it a probable sport-changer that could lower cure burden and increase compliance.
Stage 2 facts for insulin icodec showing comparable efficacy and protection to at the time-day-to-day insulin glargine U100 were released in The New England Journal of Medicine in September 2020 and at the same time documented at the European Affiliation for the Research of Diabetic issues (EASD) 2020 once-a-year meeting.
Nevertheless, some clinicians have expressed issue that an insulin that stays in the process for an overall 7 days could increase the risk for hypoglycemia.
Did Study Address Misperceptions, or Not?
Final results from the new randomized, open-label, two-period crossover review evaluating the two insulins were introduced by Thomas Pieber, MD, on June 5 at the American Diabetes Association (ADA) 82nd Scientific Classes.
In the review, insulin icodec once weekly for 6 weeks was in contrast with glargine U100 the moment every day for 11 times, with solitary evaluations of doubling and tripling the doses all through those periods. There had been no dissimilarities in hypoglycemia involving the two insulins, whilst some dissimilarities were being observed in other hormonal responses, stated Pieber, who is head of the division of endocrinology and metabolic rate at the Medical University of Graz, Austria.
Throughout the issue-and-remedy time period pursuing Pieber’s presentation, Julio Rosenstock, MD, who led the stage 2 icodec examine but was not an writer on the newer one, commented: “This study design and style…was certainly brilliant in the perception that it addresses some of the misperceptions that men and women could have with the weekly insulins.”
“Persons might imagine that…you may have more hypoglycemia because it really is weekly, so you may have a large amount of insulin on board and you’re not heading to recuperate. [This study] basically dealt with all these misperceptions…[Pieber] completely proved them completely wrong,” mentioned Rosenstock, director of the Dallas Diabetic issues Investigate Center at Clinical City in Texas.
But session moderator Rajesh Garg, MD, wasn’t confident. “After-weekly insulins are rather interesting, but hypoglycemia is the major problem and this research failed to address it to my gratification.”
The doubling and tripling evaluations have been just 24-hour periods, he explained.
“The problem will be what happens the future day…The extensive-acting insulin influence [of overdosing by two- or three-times normal] is likely to keep on the upcoming working day and the following working day [with icodec], though the insulin glargine outcome is over,” he advised Medscape Clinical News in an interview.
Garg is professor of medicine and director of clinical diabetic issues at the College of Miami, Florida.
In response to Garg’s dilemma about that in the course of the dialogue period of time right after the presentation, Pieber replied the patients ended up monitored in the scientific investigate device for 4 days soon after the dose escalations, during which time they wore steady glucose displays and ended up specified further carbohydrates. There were “really few events of moderate hypoglycemia that were being very easily compensated with oral carbohydrates,” he explained.
But Garg nonetheless was not persuaded. “We did not get people data about the incidence of hypoglycemia immediately after the research ended.”
Double, Triple the Insulin With out Big Hypoglycemia
The review bundled 43 people with sort 2 diabetic issues who had been having basal insulin with or devoid of oral glucose-reducing agents. Sufferers have been an regular age of 56 several years and 72% ended up adult men.
All oral brokers except metformin have been stopped in the course of the 7-7 days run-in time period and basal insulin doses have been optimized. Contributors were then randomized to icodec the moment weekly for 6 months or day by day glargine U100 for 11 times.
Right after a washout interval, people had been switched to the other regimen.
A double dose of icodec was given 2 weeks soon after demo initiation and a triple dose at week 5. For glargine, double doses have been offered on days 3 and 10. Glucose infusions ended up begun at 8:30 AM to retain euglycemia. At 3:00 PM, insulin and glucose were withdrawn and glycemic responses measured. If a patient’s blood glucose dropped to 45 mg/dL, they ended up specified glucose to sustain that amount of hypoglycemia.
The proportions of people who reached clinically significant hypoglycemia (described as < 54 mg/dL) with the doubled insulin dose were 40% with icodec versus 36% with glargine, which was not a signficant difference (odds ratio [OR], 1.28 P = .63). With the triple dose, those proportions were 53% with icodec versus 70% with glargine and was also not significantly different (OR, 0.48 P = .14).
Mean plasma glucose nadirs also didn’t differ with the double dose (58 mg/dL with icodec vs 59 mg/dL with glargine treatment ratio, 0.97 P = 0.07) but did with the triple dose (56 vs 52 mg/dL, respectively treatment ratio, 1.07 P < .001).
The proportions who reached a plasma glucose nadir < 54 mg/dL or experienced hypoglycemic symptoms were 53% with icodec versus 70% with glargine.
Hormone Reponses to Hypoglycemia Differed With the Two Insulins
Glucagon and growth hormone responses were comparable between the two insulins during hypoglycemia, but with icodec there was a significantly greater adrenaline response and a trend toward greater noradrenaline response compared with glargine.
Asked why the difference in adrenaline, Pieber said it wasn’t clear, but a similar phenomenon had been seen in a study of insulin degludec in type 1 diabetes.
“It may be that the flat profile has an impact on the autonomic nervous system or that signalling in the brain is different for the two insulins. It needs further study,” he said.
There were no severe hypoglycemic events during the treatment periods and no serious adverse events throughout the trial.
Phase 3a (ONWARDS) trials of insulin icodec are ongoing.
The study was funded by Novo Nordisk. Pieber has reported receiving research support from AstraZeneca, Novo Nordisk, and Sanofi, and serving on boards/advisory panels/speaker’s bureaus for Arecor and Novo Nordisk. Rosenstock has reported being an advisor or consultant to Applied Therapeutics, Boehringer Ingelheim, Hanmi Pharmaceutical, Intarcia Therapeutics, Lilly, Novo Nordisk, Oramed, and Sanofi, and receiving research support from numerous companies. Garg has reported no relevant financial relationships.
ADA 2022 Scientific Sessions. Presented on June 5, 2022.
Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape, with other work appearing in The Washington Post, NPR’s Shots blog, and Diabetes Forecast magazine. She is on Twitter: @MiriamETucker.
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