. 2001 Apr 12;2(4):198–209. doi: 10.1186/rr58

Table 1.

Summary of clinical and related trials of inhaled insulin

		Subjects
	Dosage forms/	(diabetics or
Insulin doses	delivery devices	volunteers)	Pharmacokinetic profiles and therapeutic outcome	Reference
1–2 inhalations per dose	Inhaled insulin	70 (type 1)	HbA_1c (%): 8.51 (INH), 8.53 (SC)	[29]
			Pulmonary functions: no changes
			Acceptance/preference of INH: ≥ 80%.
1–2 inhalations per dose	Inhaled insulin	51 (type 1)	HbA_1c (%): 8.7 (INH), 7.8 (SC)	[30]
			Pulmonary functions: no changes
			Acceptance/preference of INH: 92%
250 U and 500 U	AERx DMS	11 (volunteers)	T_max (min): 7 and 16 for INH 250 and 500 U, respectively	[34]
			C_max (μU/ml): 29.7 and 23.8 for INH 250 and 500 U, respectively

			tG_max (min): 66 and 76 for INH 250 and 500 U, respectively
4–6 inhalations per dose	Inhaled insulin	16 (type 2)	Baseline glucose change: 100 to 53 mg/dl (INH);	[28]
			100 to 57 mg/dl (SC)
			Pulmonary functions: no change
			Reproducibility: INH similar to SC
1–2 inhalations per dose	AERx DMS	20 (type 1)	Glucose change from baseline (mg/dl): 82 (60 min), 79 (120 min) and –11 (300 min) for AERx DMS;	[36]

			89 (60 min), 82 (120 min) and –25 (300 min) for SC
			Deleterious effect: none
1–2 inhalations per dose	Inhaled insulin	69 (type 2)	Baseline HbA_1c (%) before therapy: 9.92 (oral agent alone); 9.78 (oral agent + INH)	[38]

			Change in HbA_1c (%) after 2 weeks: –0.13 (oral agent alone); 2.28 (oral agent + INH)

100 U TI	MedTone inhaler (TI)	12 (type 2)	GIR_max (mg/kg per min): 5.8 (INH), 2.2 (SC)	[25]
	(PDC)		GIRt_max (min) = 55 (INH), 276 (SC)
	USA		Early tGIR50% (min): 17 (INH), 122 (SC)
			Late tGIR50% (min): 128 (INH), 335 (SC)
Not mentioned	Inhaled insulin	70 (type 1)	Preference of INH over SC: 81%	[32]
			Switch from SC to INH: 79%
			Continuance of SC: 21%
			Satisfaction: 38% (INH), 14% (SC)
			Convenience/ease of use: 46% (INH), 12% (SC)
Not mentioned	Inhaled insulin	Number not stated	HbA_1c (%): 8.9 (baseline), 8.0 (after 3 months), 8.1 (after 12 months), 8.0 (after 18 months), 8.0 (after 24 months)	[33]
		(type 1 and type 2)
			FEV₁ (l): 3.2 (baseline), 3.1 (after 12 months), 3.1 (after 18 months), 3.2 (after 24 months)

			DLCO (ml/min per mmHg): 25.6 (baseline), 24.7 (after 12 months), 24.7 (after 18 months), 24.4 (after 24 months)

Not mentioned	Inhaled insulin	56 (type 2)	Mean improvement in patient satisfaction (%): 38 (INH),	[31]
			14 (SC)
			INH preference to SC based on: ease of use, comfort and convenience

0.3–1.8 U/kg	AERx DMS	18 (type 1)	T_max (min): for INH 49, 48, 62 and 65 at doses 0.3, 0.6, 1.2 and 1.8 U/kg, respectively; for SC 119 at dose 0.12 U/kg	[37]

			GIR_max (mg/kg per min): for INH 1.6, 2.5, 4.7 and 6.5 at doses 0.3, 0.6, 1.2 and 1.8 U/kg, respectively; for SC 3.2 at dose 0.12 U/kg


			tGIR_max (min): for INH 94, 136, 157 and 218 at doses 0.3, 0.6, 1.2 and 1.8 U/kg, respectively; for SC 189 at dose 0.12 U/kg

25–100 U	MedTone inhaler (TI)	12 (volunteers)	GIR_max (mg/kg per min): concentration dependent	[26]
	(PDC)		GIRt_max (min): 47, 52, 56 for TI 25, 50 and 100 U, respectively; 192 for SC

			T_max (min): 12, 18, and 21 for TI 25, 50 and 100 U, respectively; for SC 153

			Bioavailability (relative to SC for 3 h): 46, 42 and 28% for TI 25, 50 and 100 U, respectively

C_max, maximum insulin concentration; DLCO, diffusion capacity; DMS, diabetic management system; FEV₁, forced expiratory volume in 1 s; GIR_max, maximum glucose infusion rate; GIRt_max, time to maximum glucose infusion rate; HbA_1c, glycated haemoglobin (glycaemic control index); INH, inhaled insulin; PDC, Pharmaceutical Discovery Corporation (Elmsford, NY, USA); SC, subcutaneous; tGIR50%, time to late half maximum glucose infusion rate; tG_max, time to maximum glycemic effect; T_max, time to maximum concentration of insulin.