Afrezza: Some questions about a new approach to prandial insulin 关于一种新型餐时胰岛素的一些问题
摘要
On June 27, the US Food and Drug Administration (FDA) announced its approval of Afrezza (insulin human) Inhalation Powder, a rapid-acting inhaled insulin to improve glycemic control in adults with diabetes mellitus, citing this as a “new treatment option [which] broadens the options available for delivering mealtime insulin”.1 Although associated with less A1c reduction than seen with subcutaneous insulin aspart in studies of 1026 type 1 diabetic patients, this did not exceed the (somewhat high) pre-specified non-inferiority margin of 0.4 percent. Among study of type 2 diabetic patients receiving oral agents, comparing Afrezza with a 70%/30% premixed biphasic Intermediate-acting/rapid-acting insulin analog, A1c reduction was comparable. The FDA will require a Boxed Warning for exacerbation of asthma and chronic obstructive pulmonary disease. Despite screening all participants in the trials for lung disease before enrollment, only giving Afrezza to volunteers who had normal lung function and who had never smoked or (22% of type 1 and 30% of type 2 diabetic participants) had quit smoking at least 6 months before starting the trial, cough, and throat pain or irritation, were common side-effects. What did the data reviewed by the FDA show about potential adverse effects? Using the FDA2 and MannKind Corporation3 Briefing Documents of the Afrezza Advisory Committee meeting in April, 27% of more than 3000 diabetic patients exposed to Afrezza versus 5% of comparators had cough. This was reported as “generally mild, dry, transient, occurred within 10 min of inhalation of the dry powder, and diminished with time,” although 4% of exposed patients (vs 0.1% of comparators) withdrew from the trials because of respiratory symptoms. The prespecified endpoint of a ≥15% decrease from baseline in forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), total lung capacity (TLC), or diffusing capacity for carbon monoxide (DLCO) was reported to have occurred in 22% versus 23