Efficacy and safety of Technosphere inhaled insulin compared with Technosphere powder placebo in insulin-naive type 2 diabetes suboptimally controlled with oral agents.

Abstract

This double-blind, placebo-controlled, randomized, multicenter, parallel-group study compared the efficacy, safety, and tolerability of Technosphere insulin with Technosphere powder as placebo in insulin-naive type 2 diabetic patients whose diabetes was suboptimally controlled with oral antidiabetic agents.
Patients (n = 126) were randomly assigned to 12 weeks of therapy with Technosphere insulin or Technosphere powder after lifestyle education on nutrition, exercise, and instructions on inhaler use. The primary efficacy outcome was change in A1C from baseline to study end, and the secondary efficacy outcome was area under the curve for postprandial glucose levels during a meal test at treatment weeks 4, 8, and 12.
A1C reduction from a mean baseline of 7.9% was greater with Technosphere insulin than with Technosphere powder (-0.72 vs. -0.30%; P = 0.003). Postprandial glucose excursions were reduced by 56% with Technosphere insulin compared with baseline, and maximal postprandial glucose levels were reduced by 43% compared with Technosphere powder. Incidences of hypoglycemia, hyperglycemia, cough, and other adverse events were low in both groups. Body weight was unchanged in both groups.
Technosphere insulin was well tolerated and demonstrated significant improvement in glycemic control with clinically meaningful reductions in A1C levels and postprandial glucose concentrations after 12 weeks of treatment.

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Efficacy and Safety of Technosphere
Inhaled Insulin Compared With
Technosphere Powder Placebo in
Insulin-Naive Type 2 Diabetes
Suboptimally Controlled With Oral Agents
JULIO ROSENSTOCK, MD1
RICHARD BERGENSTAL, MD2
RALPH A. DEFRONZO, MD3
IRL B. HIRSCH, MD4
DAVID KLONOFF, MD5
ANDERS H. BOSS, MD, MFPM6
DAVID KRAMER, PHD6
RICHARD PETRUCCI, MD6
WEN YU, MD6
BRIAN LEVY, MD, FACE6
FOR THE 0008 STUDY GROUP*
OBJECTIVE — This double-blind, placebo-controlled, randomized, multicenter, parallel-
group study compared the efficacy, safety, and tolerability of Technosphere insulin with Tech-
nosphere powder as placebo in insulin-naive type 2 diabetic patients whose diabetes was
suboptimally controlled with oral antidiabetic agents.
RESEARCH DESIGN AND METHODS — Patients (n ? 126) were randomly assigned
to 12 weeks of therapy with Technosphere insulin or Technosphere powder after lifestyle
education on nutrition, exercise, and instructions on inhaler use. The primary efficacy outcome
was change in A1C from baseline to study end, and the secondary efficacy outcome was area
under the curve for postprandial glucose levels during a meal test at treatment weeks 4, 8,
and 12.
RESULTS — A1C reduction from a mean baseline of 7.9% was greater with Technosphere
insulin than with Technosphere powder (?0.72 vs. ?0.30%; P ? 0.003). Postprandial glucose
excursions were reduced by 56% with Technosphere insulin compared with baseline, and
maximal postprandial glucose levels were reduced by 43% compared with Technosphere pow-
der. Incidences of hypoglycemia, hyperglycemia, cough, and other adverse events were low in
both groups. Body weight was unchanged in both groups.
CONCLUSIONS — Technosphere insulin was well tolerated and demonstrated significant
improvement in glycemic control with clinically meaningful reductions in A1C levels and post-
prandial glucose concentrations after 12 weeks of treatment.
Diabetes Care 31:2177–2182, 2008
C
glycemic goals. In an attempt to achieve
these standards, the American Diabetes
urrent standards of care for patients
with type 2 diabetes focus on
achieving and maintaining stringent
AssociationandtheEuropeanAssociation
for the Study of Diabetes issued a consen-
sus algorithm for type 2 diabetes manage-
ment that proposed the early use of
insulin replacement as one therapeutic
option (1). The algorithm was crafted to
more effectively and rapidly reach and
sustain A1C goals of ?7%, attempting to
overcome clinical inertia by using a tar-
get-driven strategy.
Early use of basal insulin therapy in
combination with oral antidiabetic agents
(OADs) in patients with type 2 diabetes
failing to meet A1C goals has been dem-
onstrated to achieve glycemic targets (1–
3). The APOLLO study (A Parallel design
comparing an Oral antidiabetic drug
combination therapy with either Lantus
once daily or Lispro at mealtime in type 2
diabetes patients failing Oral treatment)
also demonstrated that a prandial short-
acting insulin analog (insulin lispro) was
similartobasalinsulinanalogtherapy(in-
sulinglargine)inreducingA1Cto7%(4).
In addition, the use of prandial insulin
added to oral agents has recently been
shown to reduce A1C levels more than a
basal insulin (insulin detemir) added to
oral agents in individuals with type 2 di-
abetes, but the insulin titrations were not
properly optimized (5).
Although insulin is the most effective
therapy for reducing blood glucose levels
(1), many patients are reluctant to initiate
insulin therapy (6–8). Inhaled insulin is
an alternative to subcutaneous adminis-
trationandmayhelptoovercomebarriers
to initiation of insulin therapy (9). Tech-
nosphere technology represents a drug
delivery platform that allows pulmonary
administration of therapeutic agents
basedontheintermolecularself-assembly
of a fumaryl diketopiperazine molecule
into microparticles called Technosphere
particles. Technosphere insulin particles
(human regular insulin loaded onto the
diketopiperazine molecule) are prepared
using this technology and are optimized
for inhalation deep into the lung. They
have a uniform size distribution in that
?90%oftheparticlesareintherespirable
rangewithameanparticlediameterof2.5
?m,theydissolverapidlyatphysiological
pH (10), and they are delivered with a
● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●
From the1Dallas Diabetes and Endocrine Center at Medical City, Dallas, Texas; the2International Diabetes
Center at Park Nicollet, Minneapolis, Minnesota; the3University of Texas Health Science Center, San
Antonio, Texas; the4University of Washington Medical Center, Seattle, Washington;5Mills-Peninsula
Health Services, San Mateo, California; and6MannKind Corporation, Paramus, New Jersey.
Corresponding author: Julio Rosenstock, juliorosenstock@dallasdiabetes.com.
Received 12 February 2008 and accepted 27 July 2008.
Published ahead of print at http://care.diabetesjournals.org on 4 August 2008. DOI: 10.2337/dc08-0315.
Clinical trial reg. no. NCT00511602, clinicaltrials.gov.
*Additional members of the 0008 Study Group can be found in the APPENDIX.
B.L. is currently affiliated with Johnson & Johnson Pharmaceutical Services, LLC, Raritan, New Jersey.
© 2008 by the American Diabetes Association. Readers may use this article as long as the work is properly
cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.
org/licenses/by-nc-nd/3.0/ for details.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby
marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
E m e r g i n g T r e a t m e n t s a n d T e c h n o l o g i e s
O R I G I N A L A R T I C L E
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handheld pocket-sized inhaler. Techno-
sphereinsulinisrapidlyabsorbed(within
15 min), has a fast onset of action
(?25–30 min), and has a short duration
of action (?2–3 h) (11–14), which
closely mimics physiologic postprandial
endogenous insulin responses.
As A1C levels improve toward the
goal, the importance of therapies that re-
duce postprandial glucose (PPG) levels
increases (15,16). Early use of prandial
insulin may be increasingly common in
type2diabetesbecausecorrectionofPPG
excursions is needed to achieve an opti-
malA1Clevel(16).Technosphereinsulin
is inhaled and has uniquely favorable
pharmacokinetic properties that may en-
able more patients with type 2 diabetes to
reach glycemic goals.
We report the first and only double-
blind, placebo-controlled, randomized
trial of any inhaled insulin therapy de-
signed to evaluate the efficacy and safety
of Technosphere insulin compared with
Technosphere powder in type 2 diabetic
patients whose diabetes is suboptimally
controlled with OADs.
RESEARCH DESIGN AND
METHODS— This double-blind,
parallel-group, randomized study, con-
ducted at 21 U.S. centers, directly com-
pared efficacy and safety of 12 weeks of
prandial treatment with Technosphere
insulinorTechnospherepowderaddedto
OADs. The study complied with the Dec-
laration of Helsinki for participation in
humanresearchandreceivedappropriate
institutional review board approvals be-
fore initiation. All participants gave writ-
teninformedconsentbeforeenteringinto
the study.
Insulin-naive patients (aged 18–80
years with diabetes duration of 2–12
years), treated with at least one OAD,
were on a stable regimen for at least 3
months before enrollment. To partici-
pate, patients were required to have BMI
?38 kg/m2, A1C of 6.6–10.5%, baseline
forced vital capacity (FVC) and forced ex-
piratory volume in 1 s (FEV1) of 80–
120%ofpredictednormallevelsbasedon
spirometric reference values developed
from the National Health and Nutrition
ExaminationStudyIII(17),andabaseline
level single-breath carbon monoxide–
diffusing capacity of the lung (DLCO) of
80–120% of predicted normal (18). Pa-
tients with severe diabetes complications,
significant hepatic or renal disease, severe
or multiple allergies, chronic pulmonary
disease, AIDS, systemic autoimmune or
collagenvasculardisease,majorpsychiat-
ric disorders, and myocardial infarction
or stroke within the previous 6 months
were excluded.
Study design and treatment
After screening, subjects received com-
prehensive nutrition and exercise educa-
tion to reinforce American Diabetes
Association recommendations (19). They
were trained on the MedTone Inhaler,
whichusescartridgescontainingTechno-
sphere insulin formulated as a dry pow-
der or as Technosphere powder. The
hand-held, pocket-sized inhaler is a
breath-powered, high-resistance, dry
powder delivery device. At baseline, pa-
tients were randomly assigned to receive
cartridges containing either Techno-
sphere insulin or Technosphere powder.
Technosphere insulin cartridges con-
tained 6, 12, or 24 units of insulin as a
nominal dose (equivalent to 1.56, 3.12,
and 6.24 units of subcutaneous regular
human insulin), based on an assumed
bioavailability of 26% compared with
subcutaneouslyadministeredhumanreg-
ularinsulin(11).Subjectswereinstructed
to use the inhaler just before the first
mouthfuloffoodateachmainorsubstan-
tive meal for three to four doses total each
day. Subjects randomly assigned to Tech-
nosphere insulin were started at 6 nomi-
nalunitsofinsulinbeforeeachmealatthe
baseline visit. At subsequent visits, doses
in both groups were then adjusted con-
comitantly for each meal based on self
monitoring of PPG levels in 6- to 12-
nominal unit increments with a maxi-
mum permitted dose of 48 nominal units
per meal. Subjects were instructed to use
the same amount of study drug at each
meal after each adjustment, but study
sites did not use a common structured
titration algorithm. All subjects contin-
ued with their usual OAD regimen that
waswithheldonstudyvisitdaysuntilany
standardized meal or blood tests were
performed. No changes in OAD regimens
were allowed during the study.
At baseline, subjects underwent a
mealchallengeconsistingofamixedmeal
containing?21gfat,16gcarbohydrates,
and 14 g protein for a total of 310 kcal
(Uncle Ben’s Breakfast Bowl) that was re-
peated at weeks 4, 8, and 12. Plasma glu-
cose samples were collected at 0, 30, 60,
and 120 min after the meal and were an-
alyzed at a central laboratory for glucose
metrics and A1C.
Study end points
Theprimaryefficacyoutcomewaschange
in A1C from baseline to study end (12
weeks). The predetermined efficacy out-
come was arbitrarily defined as a mean
reduction in A1C of at least 0.6% in the
Technosphere insulin group compared
with the Technosphere powder group.
Secondaryefficacyoutcomeswerethe
PPGconcentrationsafterthemealatbase-
line and after 4, 8, and 12 weeks of treat-
ment. These concentrations were used to
calculate glucose area under the curve
from 0 to 120 min (AUC0–120) after the
startofamealandmaximumglucosecon-
centration (Cmax).
Hypoglycemia, hyperglycemia, and
cough were specifically evaluated to cap-
ture more detailed safety information.
Hypoglycemia was defined as recogniz-
able symptoms and/or a blood glucose
concentration ?63 mg/dl. Severe hypo-
glycemia was defined as an episode re-
quiring glucagon injection, glucose
administration, or help from another
individual, as well as any episode that
resulted in coma or seizures. Hyperglyce-
mia was defined as a fasting plasma glu-
cose concentration ?280 mg/dl. Plasma
glucose levels ?400 mg/dl on more than
one occasion, without adequate explana-
tion, were designated as severe hypergly-
cemia. Any plasma glucose level ?480
mg/dlresultedinautomaticwithdrawalof
thepatientfromthestudy.Hypoglycemic
or hyperglycemic episodes were not clas-
sified as adverse events unless they were
severe or necessitated study withdrawal.
Monthly spirometry conducted at
the study sites was used to measure
FEV1and FVC changes. DLCOchanges
were measured at the study sites by ex-
ternal pulmonologists at baseline and at
study end and were corrected for car-
boxyhemoglobin and hemoglobin.
Evaluations consistent with the Ameri-
can Thoracic Society recommendations
for quality control were performed on
all equipment before subject testing. An
audit of the pulmonary function testing
data was done after the study to confirm
adherence to American Thoracic Soci-
ety reporting standards.
Statistical analysis
Primary and secondary efficacy out-
comes were baseline-adjusted. With use
of a one-sided, one-sample t test, P ?
0.05 was considered significant for
within-group changes between baseline
and subsequent visits. A one-sided,
two-sample t test was used for between-
Technosphere insulin versus powder placebo
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treatment comparisons. All other statis-
tical tests of treatment effects used a
two-sided, two-sample t test. Analysis
ofvariancewasperformedforAUC0–120
and Cmaxusing SAS (version 8.2, SAS
Institute, Cary, NC). Continuous vari-
ables were summarized using descrip-
tive statistics; categorical variables are
presented as counts and percentages of
totals. Results are expressed as means ?
SD.
All randomly assigned subjects who
tookatleastonedoseofstudymedication
were included in the safety population.
Theintent-to-treat(ITT)populationcom-
prised all randomly assigned subjects
with baseline values and at least one post-
baseline value for the primary efficacy
outcome, A1C. Subjects were stratified
into two subgroups of the ITT population
for a predefined analysis as subgroup A,
with screening A1C values of 6.6–7.9%,
and subgroup B, with screening A1C val-
ues of 8.0–10.5%.
RESULTS— A total of 167 patients
were screened for the study, with 126
subjects eligible for enrollment; 107 sub-
Figure 1—Subject disposition.
Table 1—Baseline characteristics (randomized population) of subjects receiving Technosphere insulin and Technosphere placebo
ParameterTechnosphere insulin Technosphere placebo
n
Sex
61 62
Male
Female
Ethnicity
White
Black
Hispanic
Asian
Other
Age (years)
Weight (kg)
BMI (kg/m2)
A1C (%)
Medications
Sulfonylurea
Metformin
Sulfonylurea/metformin
Thiazolidinediones
Other
Number of medications
1 OAD
?2 OADs
Pulmonary function
FEV1actual (liters)
FVC actual (liters)
DLCOactual (ml ? min?1? mmHg?1)
Data are n (%) or mean ? SD (range).
39 (63.9)
22 (36.1)
43 (69.4)
19 (30.6)
40 (65.6)
7 (11.5)
12 (19.7)
1 (1.6)
1 (1.6)
39 (62.9)
3 (4.8)
14 (22.6)
5 (8.1)
1 (1.6)
55.9 ? 9.1 (34–75)
86.9 ? 13.7 (50.3–122.9)
29.7 ? 3.3 (22.0–38.1)
8.0 ? 1.2 (6.4–12.2)
53.4 ? 10.0 (26–74)
94.1 ? 15.7 (55.6–135.2)
31.4 ? 3.9 (21.0–39.3)
7.8 ? 1.1 (6.2–10.7)
39 (63.9)
43 (70.5)
9 (14.8)
17 (27.9)
6 (9.8)
33 (53.2)
37 (59.7)
10 (16.1)
22 (35.5)
8 (12.9)
22 (36.1)
39 (63.9)
27 (43.6)
35 (56.4)
2.97 ? 0.67 (1.88–4.72)
3.79 ? 0.83 (2.19–5.74)
24.99 ? 4.70 (14.83–32.95)
3.17 ? 0.77 (2.00–4.60)
4.08 ? 0.86 (2.47–5.97)
26.54 ? 5.57 (15.96–38.10)
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jects completed the study. Five subjects
withdrew from the placebo group—four
becauseofconcernsaboutthedemandsof
the study schedule and one because of
cough.Subjectdispositionissummarized
in Fig. 1. Subject baseline demographic
characteristics were comparable between
the two groups (Table 1); however, sub-
jects receiving Technosphere powder had
greater weight and BMI (P ? 0.008 and
P ? 0.014, respectively). ITT population
results are presented for efficacy, and the
full randomized population results are
presented for safety evaluation.
Efficacy
After2weeksoftreatment,meanA1Cde-
creasedby?0.7%withTechnospherein-
sulin and by ?0.3% with Technosphere
powder (P ?0.003) from baselines of 8.0
and 7.8%, respectively. Mean decreases
for ITT subgroup A (screening A1C 6.6–
7.9%) were ?0.5% from a baseline of
7.2% for Technosphere insulin (n ? 35)
and ?0.2% from a baseline of 7.1% for
Technosphere powder (n ? 35) (P ?
0.05). For subgroup B (screening A1C
8.0–10.5%), decreases were ?1.2% for
Technosphere insulin (n ? 20) and
?0.4% for Technosphere powder (n ?
18) (P ? 0.01) from baselines of 9.0 and
8.9%, respectively (Fig. 2A).
During the study, the mean dose of
Technosphere insulin increased from
the initial baseline dose of 6 nominal
units before each meal (18 nominal
units/day). The mean dose at each meal
was 20 ? 9 nominal units insulin at
week 4, 30 ? 13 nominal units at week
8, and 31.6 ? 12.9 nominal units at
week 12 (22 subjects received 6–24
nominal units and 32 subjects received
30–48 nominal units). Glucose AUC0–
120 in the Technosphere insulin group
decreased from a baseline of 4,533 ?
2,647 to 1,977 ? 2,149 min ? ?U?1?
ml?1(P ? 0.0001) (Fig. 2B); the glu-
cose Cmaxwas 43% less with Techno-
sphere insulin than with Technosphere
powder: 34 vs. 60 mg/dl (P ? 0.0001),
respectively (data corrected by sub-
tracting the baseline glucose value at 0
min).
Safety
As shown in Table 2, incidences of hy-
poglycemia and hyperglycemia were
similar for both groups, with no signif-
icant between-group differences (P ?
0.321 and P ? 0.871, respectively).
Technosphere insulin was associated
with an incidence of hypoglycemic epi-
sodes per month similar to that with
Technosphere powder (0.69 vs. 0.86,
respectively; P ? 0.346).
Coughing episodes were similar in
both groups (Table 2). Eighteen of 61
(29.5%) Technosphere insulin subjects
and17of62(27.4%)Technospherepow-
der subjects experienced ?1 coughing
episode. Most episodes of coughing were
reported to occur within 10 min of study
drug administration (41 of 63 episodes
with Technosphere insulin and 89 of 113
with Technosphere powder). Three sub-
jects in each group had sputum produc-
tion. One subject in the Technosphere
insulin group withdrew because of
cough.
Mean changes from baseline in FEV1
were ?0.04 liter for Technosphere insu-
lin (P ? 0.143) and ?0.01 liter for Tech-
nosphere powder (P ? 0.74); mean
changes from baseline in FVC were
?0.04liters(P?0.218)and?0.02liters
(P ? 0.55). Mean DLCOvalues decreased
slightly in both groups (mean change ?
0.02 ml ? min?1? mmHg?1with Techno-
sphere insulin [P ? 0.943] and 0.67 ml ?
min?1? mmHg?1with Technosphere
powder [P ? 0.042]). These changes
were not considered clinically relevant
(Table 2).
After 12 weeks of treatment with
Technosphere insulin or Technosphere
Figure 2—A: Reductions in A1C. B: Postprandial glucose excursions. f, Technosphere placebo;
?, Technosphere insulin.
Technosphere insulin versus powder placebo
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powder, no increase in body weight was
reported, and weight change was not sig-
nificantlydifferentbetweengroups(?0.1
vs. ?0.9 kg, respectively [P ? 0.071])
(Table 2). No clinically relevant changes
were observed in clinical laboratory mea-
surements in either group.
CONCLUSIONS — This is the first
double-blind, placebo-controlled, ran-
domized inhaled insulin study (Techno-
sphere insulin versus Technosphere
powder) ever reported to assess the effi-
cacyandsafety/tolerabilityprofileininsu-
lin-naive type 2 diabetic patients
suboptimally controlled with OADs
alone. Technosphere insulin resulted in
significant reductions in A1C compared
with Technosphere powder over a 12-
week treatment period, with greater re-
ductions in subjects with higher baseline
A1C values. Overall, the hypoglycemia
rate was low and similar between Tech-
nosphere insulin and Technosphere
powder.
The significant A1C reductions
(0.7%) with Technosphere insulin were
clinically meaningful, especially consid-
ering the mildly elevated A1C at baseline
(8.0% for the Technosphere insulin
group and 7.8% for the Technosphere
powder group). This modestly elevated
baseline A1C may explain why the arbi-
trary predetermined superiority limit of
an A1C reduction ?0.6% (Technosphere
insulin versus Technosphere powder)
was not achieved over a 12-week treat-
ment period. Additional factors that may
have contributed to not achieving the
0.6% A1C difference between groups in-
cludetherelativelyshorttreatmentperiod
(12 weeks), the A1C reduction in the pla-
cebo group due to the study effect and
dietary/diabetes education (20), the unfa-
miliarity of the investigators with adjust-
ing the dose of inhaled pulmonary
Technosphere insulin, and the lack of a
commonstructuredinsulintitrationalgo-
rithm for all sites. Of note, Technosphere
insulin doses were not increased to the
maximum permitted level of 48 nominal
units per meal in ?40% of subjects. This
lack of maximal dosing may have been
due to the investigators’ caution with the
apparent higher numerical Technosphere
insulin doses.
Previous studies have demonstrated
that Technosphere insulin has a much
morerapidabsorptionwithashortertime
to Cmaxthan subcutaneous human regu-
lar insulin (21,22). This pharmacokinetic
profile, which more closely approximates
early-phaseinsulinrelease,hasthepoten-
tialtoresultinsignificantimprovementin
PPG excursions. Indeed, this study dem-
onstrated that the PPG excursions with
Technosphere insulin after meals were
less than half of those with Technosphere
powder. This reduction in PPG exposure
wouldbeexpectedtocontributetosignif-
icantA1Creductions,especiallywhenthe
A1C level is mildly elevated, as was dem-
onstrated in this study.
BothTechnosphereinsulinandTech-
nosphere powder were well tolerated in
this study. Technosphere insulin and
Technosphere powder were associated
with mild, transient cough (29.5 and
27.4%ofsubjects,respectively),butthere
wasonlyonediscontinuationintheTech-
nosphere insulin group. Technosphere
insulinandTechnospherepowderhadno
clinically meaningful effects on short-
termpulmonaryfunction,asmeasuredby
either spirometry or diffusion capacity,
after12weeksofexposure.Theincidence
of hypoglycemia was comparable be-
tween groups despite greater A1C reduc-
tions with Technosphere insulin, and no
clinically severe hypoglycemia was re-
portedineithergroup.Nootherclinically
relevant adverse events occurred during
the study. Despite improvement in glyce-
miccontrol,subjectsintheTechnosphere
insulin group did not gain weight com-
pared with those in the Technosphere
powder group.
Technosphereinsulinisanewinsulin
delivery system with a unique pharmaco-
kinetic profile compared with all cur-
rently available insulins. Patients with
type 2 diabetes could potentially benefit
frominitiationofprandialinsulintherapy
withaninsulinthatmimicstheperipheral
insulin level that reflects early insulin se-
cretion. Such an insulin would be an im-
portantadditiontothearmamentariumof
diabetestherapies.Injectedprandialinsu-
linaddedtooralagentshasbeenshownto
potentially reduce A1C levels in patients
with type 2 diabetes more effectively than
basal insulin but has resulted in more hy-
poglycemia and weight gain (5). It re-
mains to be determined whether
Technosphere insulin, with its unique
pharmacologicprofile,mightresultinless
hypoglycemia and weight gain while still
effectively lowering the A1C in patients
with type 2 diabetes.
This first proof-of-concept trial dem-
onstrated that Technosphere insulin is
well tolerated and substantially reduced
A1C levels and meal-related glucose ex-
cursionsintype2diabeticpatients.Tech-
nosphere insulin may become an
important treatment option in type 2 di-
abetes.Larger,long-termclinicaltrialsare
inprogresstofurtherevaluatetheefficacy
and safety of Technosphere insulin re-
ported in this study.
Table 2—Safety outcomes for Technosphere insulin and Technosphere placebo groups
Parameter
Technosphere
insulin
Technosphere
placebo
n
Hypoglycemia
Subjects with ?1 event
Rate per month
Hyperglycemia
Subjects with ?1 event
Rate per month
Weight, mean change from baseline (kg)
Cough
Subjects with ?1 episode
Total episodes
Episodes considered related to study drug
Occurred within 10 min of inhalation
Pulmonary function
FEV1actual, mean change from baseline
(liters)
FVC actual, mean change from baseline
(liters)
DLCOactual, mean change from screening,
ml/min ? mmHg (SD)
Data are n (%), mean ? SD, or n.
61 62
26 (42.6)
0.7 ? 1.6
22 (35.5)
0.9 ? 1.9
10 (16.4)
0.3 ? 0.8
–0.1 ? 2.0
10 (16.1)
0.22 ? 0.9
–0.9 ? 2.9
18 (29.5)
63
45
41
17 (27.4)
113
93
89
–0.04 ? 0.20 –0.01 ? 0.20
–0.04 ? 0.22 –0.02 ? 0.21
–0.02 ? 2.32–0.67 ? 2.33
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