Place of technosphere inhaled insulin in treatment of diabetes

Table 1 Clinical trials of technosphere insulin using Gen2 device

Ref.	Rosenstock et al[9]	Bode et al[10]
Design	Randomized, double-blind, placebo-controlled, 24 wk-duration	Randomized, open-label, 24 wk-duration
Type of diabetes	Type 2	Type 1
Intervention	TI (n = 177) vs placebo (n = 177), both groups were on oral agents	TI (n = 174) vs prandial aspart (n = 170). Both groups received basal insulin (NPH or detemir, or glargine)
Mean HbA1c levels at baseline	8.26%	7.93%
Reduction in HbA1c vs baseline	-0.8% with TI and -0.4% with placebo	-0.21% with TI vs -0.4% with aspart
Reduction in mean HbA1c with TI vs comparator	-0.4% vs placebo (95%CI: -0.57 to -0.23)	0.19% vs aspart (95%CI: 0.02 to 0.36)
Proportions of patients reaching HbA1c ≤ 7%	38% with TI vs 19% with placebo (P = 0.0005)	18% with TI vs 31% with aspart (P = 0.01)
Proportions reporting adverse effects	61% TI vs 51.1% placebo	58% TI vs 43% aspart
Proportions of patients reporting hypoglycemia	67.8% TI vs 30.7% placebo (P < 0.0001)	96% TI vs 99.4% aspart (P = 0.06)
Proportions of patients reporting cough	23.7% TI vs 19.9% placebo (difference not statistically significant)	31.6% TI vs 2.3% aspart P < 0.05
Withdrawal due to cough	1.1% with TI vs 3.4% with placebo	5.7% with TI vs 0% with aspart
Change in mean weight	+ 0.5 kg TI vs -1.1 kg placebo (P < 0.0001)	-0.4 kg with TI vs +0.9 kg aspart (P = 0.01)
Change in mean FEV1 (L)	- 013 L with TI vs -0.04 L with placebo	-0.07 L with TI vs -0.04 L with aspart
Withdrawal due to adverse effects	4% with TI vs with 5.1% placebo	9.2% with TI vs with 0% aspart

FEV1: Forced expiratory volume in 1 s; TI: Technosphere insulin; HbA1c: Hemoglobin A1c.

Table 2 Clinical trials of technosphere insulin using the Med-Tone device

Ref.	Raskin et al[14]	Rosensensk et al[12]
Design	Randomized, open label, 2 yr-duration, pulmonary safety trial	Randomized, open-label, 52-wk duration
Type of diabetes	Types 1 and 2	Type 2
Groups of subjects and intervention	TI (n = 938), usual diabetes care (n = 951), control subjects without diabetes (n = 164)	Glargine qhs + prandial TI (n = 334) vs1biaspart insulin bid (n = 343)
Proportions of patients with adverse effects	79% TI vs 71% usual care	84% TI vs 89% biaspart
Mean HbA1c at baseline	8.7%	8.7%
Reduction in HbA1c vs baseline	-0.59% with TI and -0.50% with usual care	-0.68% with TI/glargine vs -0.76% with biaspart
Reduction in HbA1c with TI vs comparator	0.09% (not significant)	0.07% (not significant)
Proportions of patients reporting hypoglycemia	39.5% TI vs 39.1% usual care	48% glargine/TI vs 69% biaspart. OR 0.4 (95%CI: 0.3-0.5)
Proportions of patients reporting cough	27.8% TI vs 4.4% usual care	33% glargine/TI vs 6% biaspart
Withdrawal due to cough	4.7% TI vs 0% usual care	2% glargine/TI vs 0% biaspart
Change in mean weight	Not reported	+ 0.9 kg glargine/TI vs +2.5 kg biaspart. Mean difference 1.6 kg (95%CI: -2.4 to -0.7)
Decline in mean FEV1 (liters)	More decline in TI group vs usual care. Mean difference 0.037 (95%CI: 0.017-0.06)	-0.13 glargine/TI vs -0.09 biaspart (difference not significant)
Withdrawal due to adverse effects	11% TI vs 0.6% usual care	9% glargine/TI vs 4% biaspart

¹Biaspart insulin is pre-mixed insulin composed of 70% insulin protamine suspension + 30% insulin aspart. FEV1: Forced expiratory volume in 1 s; TI: Technosphere insulin; HbA1c: Hemoglobin A1c.

Table 3 Candidate patients for technosphere insulin

Patients with type 1 diabetes who are taking basal insulin once daily, but prefers to take their prandial insulin in the inhaled formulation

Patients with type 2 diabetes uncontrolled on oral agents, and are reluctant to start subcutaneous insulin due to needle phobia or other reasons

Patients already on subcutaneous prandial insulin who develop frequent late post-prandial hypoglycemia (4-5 h after meals)

Any patient who develops skin reactions to insulin subcutaneous injections such as lipoatrophy or lipohypertrophy

In combination of automated artificial pancreas to provide rapid insulin delivery right after meals[20]

Table 4 Advantages and limitations of technosphere insulin

Advantages

Relatively easy and non-painful administration

Flexible timing of administration either inhaled directly before meals or within 20 min after finishing a meal[10]

Hypoglycemia is less frequent than subcutaneous insulin, particularly late postprandial hypoglycemia

Weight gain is slightly less pronounced than subcutaneous insulin

Limitations

Frequent cough (24%-33% of patients)

Available only as prandial short-acting insulin. Hence, long-acting basal subcutaneous insulin should be added in patients with type 1 diabetes

Slightly less effective than subcutaneous insulin

Need for baseline and then serial pulmonary function testing

Safer to switch to subcutaneous insulin in case of upper or lower respiratory infections to avoid exacerbation of the disease and possible unreliable pulmonary absorption

No data available for pediatric and pregnant populations

Limited strength options and difficult fine titration of doses

Lack of long-term safety data

High cost, e.g., average price of ninety 4-unit cartridges and 2 inhalers is $271[21]