Technosphere insulin effectively controls postprandial glycemia in patients with type 2 diabetes mellitus.

BACKGROUND: This pilot trial was designed to determine if an optimal dose of Technosphere(®) insulin (TI) inhalation powder (MannKind Corp., Valencia, CA) could be used regardless of variation in meal carbohydrate (CHO) content. SUBJECTS AND METHODS: In total, eight subjects (seven men, one woman) with type 2 diabetes were enrolled. Subjects underwent dose optimization meal challenge (MC) visits (100% CHO) and MCs with varied CHO meal contents (50%, 200%, and 0% calculated CHOs). Primary end point was change in postprandial glucose (PPG) excursions. Baseline demographics were 60±7 years of age, diabetes duration of 12.3±4.27 years, hemoglobin A1c (A1C) of 7.82±1.04%, and body mass index of 31.3±5.48 kg/m(2). RESULTS: Maximum mean PPG excursions for the nominal 100% CHO meals were -13±15 mg/dL for breakfast (B) and -14±15 mg/dL for lunch (L), similar to those after 50% CHO meals (B, -17±16 mg/dL; L, +14±10 mg/dL). The largest excursions occurred during 200% CHO meals and remained below American Diabetes Association targets (B, +19±16 mg/dL; L, +32±29 mg/dL). During 15 of the MCs, subjects took their usual TI dose and then had no meal (0% CHO). For the 0% CHO MCs, the largest mean PPG excursion were -33±9 mg/dL at 60 min (B) and -31±10 mg/dL at 60 and 90 min (L). Mean A1C dropped from 7.82±1.04% at the Week 1 visit to 6.18±0.46% (P=0.00091) at the Week 19 visit. CONCLUSIONS: Results in eight patients suggest that once an optimal dose of TI is determined, type 2 diabetes patients can ingest meals with a wide range of CHO content or even skip meals without severe hypoglycemia. During this pilot study TI therapy improved A1C by -1.63% (P=0.00091) during 19 weeks of treatment.

Confessions of a serial entrepreneur: a conversation with Alfred E. Mann. Interview by Molly Joel Coye.

In this wide-ranging interview, Alfred Mann describes the activities of several medical technology enterprises with which he is engaged. Several of them are companies that he formed; one is a nonprofit foundation, the Alfred E. Mann Foundation for Biomedical Engineering, founded to establish research-oriented institutes on a dozen university campuses and support their work in developing marketable innovations. Mann discusses the need to consider the cost implications of technology, in the context of U.S. health system reform, and describes several important innovations that have emerged from his companies over the years.

Technosphere/Insulin--a new approach for effective delivery of human insulin via the pulmonary route.

The development of pulmonary insulin formulation offers an attractive alternative to the current requirement of repeated subcutaneous (s.c.) injections for insulin administration. Technosphere/Insulin is a formulation of regular human insulin that was designed to produce an efficient transport of insulin across the respiratory epithelium into the systemic circulation. Several studies using the euglycemic clamp technique were performed in healthy volunteers and patients with Type 2 diabetes to assess the pharmacokinetic and pharmacodynamic properties of Technosphere/Insulin. The investigations revealed a very rapid systemic insulin uptake (insulin T(max) approximately 12-14 min), a fast onset of action (maximum activity approximately 20-30 min), and a short duration of action (approximately 2-3 h) in healthy volunteers and in patients with Type 2 diabetes. In the first study, employing a commercially available inhaler, the relative bioavailability (compared with s.c. injections) was initially reported to be 26% for the first 3 h and 16% for the entire observation period of 6 h. With the development of a specific inhaler adapted to the physical properties of Technosphere/Insulin, the MedTone Inhaler, relative bioavailability was 50% for the first 3 h and 30% over the entire 6-h period. A clear linearity of systemic insulin uptake was observed in a study employing 12 healthy volunteers inhaling doses of 25, 50, and 100 IU. Repeated inhalation of 100 IU of Technosphere/Insulin by 12 patients with Type 2 diabetes revealed a lower variability in comparison with published s.c. injection data from healthy volunteers. This new Technosphere/Insulin formulation was well tolerated, and no serious adverse events were reported in any of the investigations. Given its attractive time-action profile, Technosphere/Insulin may become a suitable alternative to s.c. injection for prandial insulin delivery, especially in patients with Type 2 diabetes, if the long-term safety, tolerability, and efficacy of this pulmonary insulin are established and confirmed in future studies.