All About Afrezza®: The New Insulin Inhalation Powder

Devada Singh-Franco, PharmD, CDE

Disclosures

August 19, 2014

Question

What should we know about Afrezza®?

Response from Devada Singh-Franco, PharmD, CDE
Associate Professor, Nova Southeastern University College of Pharmacy; Clinical Pharmacist, Broward Health Medical Center, Fort Lauderdale, Florida

Introduction

Afrezza®, a dry-powder formulation of recombinant human regular insulin, was recently approved by the US Food and Drug Administration.[1] Afrezza is indicated for use in adults ≥ 18 years of age with type 1 or type 2 diabetes mellitus (T1DM or T2DM); however, in those with T1DM, Afrezza must be used in combination with long-acting insulin.[2] Afrezza is not indicated for use in children, women who are pregnant or breastfeeding, or patients with diabetic ketoacidosis.[2]

After inhalation, Technosphere® insulin (TI) particles will reach the lung and dissolve on contact, with subsequent rapid absorption into systemic circulation.[2,3] Per the manufacturer, the amount of insulin delivered to the lung depends on individual patient factors. It is considered an ultra-rapid-acting insulin because the onset of action is 12-15 minutes, with a peak of about 60 minutes and duration of activity of about 2.5-3 hours.[2]

Efficacy and Tolerability

In an abstract presented at the 44th General Assembly of the European Association for the Study of Diabetes, Kapsner and colleagues[4] reported outcomes from a 52-week study of patients with T1DM (baseline A1c > 7.0% and ≤ 11.0%) who were randomly assigned to receive basal insulin glargine plus a prandial rapid-acting analogue (RAA) (n = 288) or prandial TI (n = 301). The dose of TI and dose titration protocols for basal, RAA, or TI were not provided.

At study end, a reduction in A1c was reported in the TI/glargine and the RAA/glargine groups (-0.17% vs -0.47%, respectively). Changes in fasting plasma glucose (FPG) and weight were favorable for those receiving TI compared with RAA (-45 mg/dL vs -23.4 mg/dL; P = .0052 and -0.5 kg vs +1.4 kg; P < .0001, respectively). Postprandial glucose (PPG) at 1 hour was 165.6 mg/dL in patients receiving TI vs 201.6 mg/dL in patients receiving RAA (P = .0203). However, data from 2-hour PPG were not provided. Mild to moderate hypoglycemia occurred less frequently in those receiving TI vs RAA (85.67% vs 92.65%, respectively; P = .0091), but severe hypoglycemia occurred similarly between the groups (32.76% vs 37.50%, respectively).[4]

In an open-label, 52-week study, 677 patients with T2DM (baseline A1c, 8.7%) were randomly assigned to receive prandial TI plus bedtime insulin glargine vs twice-daily premixed aspart 70/30.[5] Standardized meal challenge was done to assess PPG response, with administration of preprandial TI within 90 seconds of ingesting the meal or premixed aspart insulin 15 minutes before the meal.

  • Study dosing for glargine plus TI:

    • Basal insulin: 50% of the total daily dose

    • TI insulin: 50% of the total daily dose distributed across main meals and individually adjusted in 15-unit increments (maximum, 90 units per meal) on the basis of self-monitoring of blood glucose. Cartridges of 15 units and 30 units were provided to patients (15 units of TI is about 3.8 units of subcutaneous [SC] rapid-acting insulin, based on bioequivalence of 24%-28%)

  • Study dosing for premixed aspart 70/30: dose adjusted on target FPG and predinner plasma glucose values of 79-110 mg/dL

By study end, patients assigned to TI were receiving 198 ± 74 units per day. The mean daily dose of glargine was 47 ± 25 units. Those assigned to premixed aspart 70/30 received 88 ± 48 international units per day. Patients in both groups had a statistically significant reduction in A1c (-0.59% with TI/glargine vs -0.71% with premixed aspart 70/30) and FPG (-32 mg/dL TI/glargine vs -18.4 mg/dL premixed aspart 70/30) vs baseline, and the difference in FPG was in favor of TI/glargine (P = .0029) Although the TI/glargine group also experienced a significant reduction in 1-hour PPG, it took almost 6 hours for PPG to reach preprandial levels. In comparison, PPG in the premixed aspart 70/30 group reached the preprandial level in 4 hours.[5]

Weight gain occurred in both groups (+0.9 kg with TI/glargine vs +2.5 kg with premixed aspart 70/30), but was greater for those on premixed aspart 70/30 (difference between groups, -1.6 ± 0.4 kg; 95% confidence interval (CI), -2.4 to -0.7; P = .0002). Cough was reported more frequently in those receiving inhaled insulin (33% vs 6%); it occurred most frequently during the first 10 minutes of inhalation, usually during the first week of therapy, and was typically nonproductive. However, withdrawal owing to any adverse events was more likely among patients receiving TI/glargine than those receiving premixed aspart (9% vs 4%, respectively), with cough as the main reason for discontinuation.[5]

Hypoglycemia of any severity was most likely to occur with premixed aspart 70/30 vs TI/glargine (odds ratio, 0.417; 95% CI, 0.303-0.573), and the occurrence of severe hypoglycemic events at any time of day was higher with premixed aspart 70/30.[5]

Patients were included in the study if the forced expiratory volume in 1 second (FEV1) and diffusing lung capacity for carbon monoxide (DLCO) were ≥ 70% of predicted values and total lung capacity was ≥ 80% of predicted values. At study end, there was a nonsignificant reduction in FEV1, DLCO, and forced vital capacity in both treatment groups.[5]

Additional efficacy and tolerability data can be found in several publications.[6,7,8,9]

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