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Inhaled insulin improves glucose control in type 1 diabetes

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October 12, 2018

Compared with multiple daily insulin injections, inhaled insulin was shown to provide benefits for adults with type 1 diabetes, including improved postprandial glucose levels, lower daytime glucose variability and less hypoglycemia, according to a study published in Diabetes Technology & Therapeutics.

“Ideally, use of an ultra-rapid-acting prandial insulin that closely mimics the time action profile of normal insulin secretion and human physiology will lower postprandial glucose excursions without any delayed hypoglycemia,” Halis Kaan Akturk, MD, assistant professor of medicine and pediatrics at the Barbara Davis Center for Diabetes at the University of Colorado Denver, and colleagues wrote. “The faster onset of action and shorter duration profile of [inhaled insulin (Afrezza, MannKind)], when compared with [rapid-acting insulin analogues], may provide a flexible approach for patients to optimize postprandial glucose control without an increased risk of hypoglycemia.”

Akturk and colleagues enrolled 60 adults with type 1 diabetes for at least 6 months to a 4-week pilot, randomized, multicenter trial from June to December 2017. All participants had HbA1c between 6.5% and 10%, had stable insulin dose and used insulin degludec (Tresiba, Novo Nordisk) or insulin glargine (Lantus, Sanofi) as basal insulin.

Participants were randomly assigned inhaled insulin (n = 26; mean age, 41 years; mean diabetes duration, 21 years; mean total daily basal insulin dose, 27.9 U; mean total daily bolus insulin dose, 21.8 U) or insulin aspart (n = 34; mean age, 42 years; mean diabetes duration, 19 years; mean total daily basal insulin dose, 22.7 U; mean total daily bolus insulin dose, 21.3 U). During the 4 weeks of the trial, participants wore real-time continuous glucose monitors; there were seven follow-up examinations, including four in-person visits and three by phone. Four participants in the inhaled insulin group dropped out of the trail or had missing data and were not included in the final analysis.

Using linear regression analysis of data from CGM, researchers observed a lower glucose standard deviation (P = .01) and percentage of time spent in hypoglycemia (HbA1c < 60 mg/dL, P = .02; HbA1c < 50 mg/dL, P = .04) in the inhaled insulin group vs. the insulin aspart group. Mean sensor glucose readings, percentage of time with HbA1c less than 70 mg/dL and percentage of time in hyperglycemia were nonsignificantly lower in the inhaled insulin group. Participants in the inhaled insulin group lost more weight (0.83 kg per day) compared with the insulin aspart group (0.57 kg per day; P < .0001).

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Participants in the inhaled insulin group were further segmented based on adherence to the study protocol, with 15 of the original group meeting the compliance criteria. The researchers observed more time in range, lower glucose standard deviation and less time in hyperglycemia in the inhaled insulin-compliant group compared with both the insulin aspart (P = .009) and inhaled insulin-noncompliant (P = .03) groups. The inhaled insulin-compliant group also had lower postprandial glucose than the insulin aspart group (P = .05), but a relatively similar level compared with the inhaled insulin-noncompliant group.

Postprandial glucose levels differed the most between the two groups 60 to 90 minutes after a meal, with postprandial glucose levels increasing in the insulin aspart group during the first hour after a meal, and dropping to their lowest point for the inhaled insulin group, and for the inhaled insulin-compliant group, in particular.

The researchers also analyzed the effects of the two treatment types based on meal time. Although postprandial glucose levels were lower in the inhaled insulin group at breakfast (P = .04) and lunch (P = .001), the same significance was not found at dinner (P = .75).

“The potential reasons for this observation at dinnertime include the fear of hypoglycemia overnight — an experience that might be anticipated with an insulin with longer duration of action,” the researchers wrote. “However, as the vast majority of [type 1 diabetes] patients currently use subcutaneous [rapid-acting insulin analogue], many may be reticent to use postprandial corrections later in the day. As [inhaled insulin] has a shorter duration and a faster action profile compared with currently available mealtime injectable insulins, this may offer an advantage to both minimize the risk of nocturnal hypoglycemia and increase the use of supplemental or corrective doses before bedtime.” – by Phil Neuffer

Disclosures: The study was supported by MannKind. Akturk reports he received a research grant from MannKind related to this study. Please see the study for all other authors’ relevant financial disclosures.