February 24, 2021
2 min read
MannKind Corp. provided financial support for this study. Hoogwerf reports he is a consultant for MannKind Corporation and holds stock options in Eli Lilly and Co. Please see the study for all other authors’ relevant financial disclosures.
Among adults with type 2 diabetes, inhaled insulin was associated with HbA1c reductions similar to those with insulin aspart, fewer hypoglycemic episodes and lower body weight, according to a study published in Endocrine Practice.
“Technosphere insulin (Afrezza, MannKind Corp.) affords an alternative to injectable prandial insulin, especially for patients who may prefer inhaled insulin over injectable insulin,” Byron J. Hoogwerf, MD, FACP, FACE, professor emeritus in diabetes, endocrinology and metabolism at the Cleveland Clinic, told Healio. “[In this study] cough was the major side effect with Technosphere [inhaled] insulin, but was generally not severe enough to result in discontinuation of Technosphere insulin and was less of a problem over time.”
Hoogwerf and colleagues conducted a 24-week randomized controlled trial with adults aged 18 to 80 years who had type 2 diabetes for at least 2 years and were prescribed insulin for at least 3 months. The study began with a 4-week period in which insulin glargine doses were stabilized. Those who took less than 60 daily doses of subcutaneous insulin before the study initially received 10 doses of insulin glargine, and those who used 60 or more daily doses before the trial started at 20 doses of insulin glargine. After the 4-week stabilization, participants were randomly assigned to a cohort receiving inhaled rapid-acting mealtime insulin (Afrezza, MannKind Corp.) plus insulin glargine (n = 151) or a control group receiving insulin aspart (NovoLog, Novo Nordisk) plus insulin glargine (n = 158). Doses were taken before each meal and with another meal or snack as needed. Inhaled insulin was administered using the MedTone device (Mannkind Corp.), with participants receiving 15 U or 30 U of insulin. Dosage could be increased up to 60 U per meal. The insulin aspart cohort started on 4 U to 8 U that could be increased by 2 U or 4 U based on home monitoring. After the trial period concluded, a 24-week safety period followed with participants receiving standard care.
Mean HbA1c declined from 8.9% to 7.9% in the inhaled insulin group during the trial period, whereas the control group’s mean HbA1c dropped from 9% to 7.7%. The treatment difference between the cohorts was not statistically significant. The inhaled insulin group had a mean body weight reduction of 0.78 kg during the trial, whereas the control cohort had a mean body weight increase of 0.23 kg (P = .0007). The mean daily dose of insulin glargine was comparable in both groups, and there were no differences in blood chemistry or lipid profiles.
Fewer participants in the inhaled insulin group reported at least one hypoglycemic event during the trial compared with the control cohort (43% vs. 54%, P = .035). There were 29 participants in the inhaled insulin cohort who reported at least one coughing episode compared with six in the insulin aspart group. The coughing episodes were intermittent or single in 87% of the participants, with six inhaled insulin participants reporting continuous coughing.
“[Technosphere insulin] may also be a consideration for patients for whom the rapid effect of inhaled insulin on postprandial glucose control may be a consideration in their management,” Hoogwerf said. “This effect after a meal was not evaluated in the current study, but has been demonstrated in studies that have analyzed meal tolerance tests compared to subcutaneous insulin analogues. It appears that Technosphere insulin may more closely approximate the physiological insulin response than other injectable prandial insulins.”
Hoogwerf said more research is needed to assess how inhaled insulin dosing compares to multiplying prandial injection insulin, since inhaled insulin comes in cartridges labeled as 4, 8 and 12 U. The timing of inhaled insulin is another topic researchers should explore.
“There are data from small studies demonstrating that Technosphere insulin may be administered immediately before a meal and may be used to control postprandial hyperglycemia,” Hoogwerf said. “Studies that refine the understanding of this rapid effect should include use with acute hyperglycemia, postprandial hyperglycemia and treatment of hyperglycemia with insulin pump therapy.”
For more information:
Byron J. Hoogwerf, MD, FACP, FACE, can be reached at email@example.com.