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Barriers to Insulin Progression
1
Polinski et al
Jennifer M. Polinski, ScD, MPH
Benjamin F. Smith, BA
Bradley H. Curtis, DDS, MPH, PhD
John D. Seeger, PharmD, DrPH
Niteesh K. Choudhry, MD, PhD
John G. Connolly, BS
William H. Shrank, MD, MSHS
From Brigham and Women’s Hospital, Boston, Massachusetts (Dr Polinski, Dr Smith, Dr Seeger, Dr Choudhry, Dr Connolly, Dr Shrank); Harvard Medical School, Boston, Massachusetts (Dr Polinski, Dr Seeger, Dr Choudhry, Dr Shrank); and Eli Lilly and Company, Indianapolis, Indiana (Dr Curtis).
Correspondence to Jennifer M. Polinski, ScD, MPH, Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital, 1620 Tremont Street, Suite 3030, Boston, MA 02120 ([email protected]).
Acknowledgments: Eli Lilly and Company, study F3Z-MC-B010. Dr Curtis is a Eli Lilly employee and holds stock in Eli Lilly. The first author, Dr Polinski, retained full control over the design and conduct of the study; collection, analysis, and interpretation of the data; and preparation, review, and submission of the final manuscript.
A supplementary appendix for this article is available on The Diabetes Educator Web site at http://tde.sagepub.com/supplemental.
DOI: 10.1177/0145721712467696
© 2012 The Author(s)
Barriers to Insulin Progression Among Patients With Type 2 DiabetesA Systematic Review
Purpose
Treatment guidelines recommend insulin progression (switching from basal to a premixed insulin regimen, adding bolus doses, and/or increasing dosing frequency) to achieve A1C targets as type 2 diabetes progresses, but fewer patients are being progressed than would be indi-cated based on their disease status. This systematic review proposes 2 questions regarding insulin progres-sion among patients with type 2 diabetes: (1) What are the patient, provider, and health system barriers to insulin progression? (2) Do insulin progression barriers differ between insulin-naive and insulin-experienced patients?
Methods
We conducted a systematic review in the MEDLINE, EMBASE, Science Citation Index, PsycINFO, CINAHL, and Cochrane Library databases through July 2011.
Results
Of 745 potentially relevant articles, 10 met inclusion criteria: 7 evaluated patient and 2 evaluated provider bar-riers, and 1 was an intervention to reduce barriers among physicians. Patients with prior insulin experience had fewer barriers arising from injection-related concerns and worries about the burden of insulin progression than did insulin-naive patients. Physician barriers included concerns about patients’ ability to follow more compli-cated regimens as well as physicians’ own inexperience with insulin and progression algorithms. The cross- sectional nature, narrow scope, and failure of all studies
The Diabetes Educator OnlineFirst, published on November 27, 2012 as doi:10.1177/0145721712467696
The Diabetes EDUCATOR
2
Volume XX, Number X, Month/Month XXXX
to examine patient, provider, and health systems barriers concurrently limited both barrier identification and an assessment of their impact on progression.
Conclusions
Patient and physician experience with insulin and diabe-tes/insulin education were associated with fewer per-ceived barriers to insulin progression. Future studies should use multilevel longitudinal designs to quantify the relative impact of potential patient, provider, and health system factors on progression and health outcomes.
The worldwide prevalence of type 2 diabetes continues to increase, bringing with it a substantial impact on morbidity, mortality, and health care costs. It is estimated that 329 million patients will have type 2 diabe-
tes by the year 2030, approximately double the number from year 2000; this projected increase is largely driven by the inexorable process of aging rather than changes in lifestyle factors, so it is likely a conservative estimate.1 More than 3 million deaths per year are attributable to diabetes,2 making it the fifth leading cause of death worldwide.3 In the United States, diabetes-related health expenditures exceeded $174 billion in 2007, with $58 billion spent on preventable complications such as stroke, heart disease, and kidney failure.4
When initial lifestyle modifications and oral antidia-betic medications are not sufficient to maintain glycemic control in patients with type 2 diabetes, expert consensus guidelines and evidence-based algorithms recommend insulin initiation and subsequent insulin progression (switching from a basal insulin regimen to a premixed insulin, adding bolus doses, and/or increasing the fre-quency of dosing) to achieve hemoglobin A1C targets.5-7 However, observational studies in real-world settings reveal gaps in the implementation of these treatment guidelines.8-11 A population-based study in Germany and the United Kingdom found that only 25% of patients who did not meet A1C goals on a basal insulin regimen had their insulin therapy progressed.8,10 A US academic medical center-based study found that fewer than 50% of patients whose diabetes status warranted insulin progres-sion were actually progressed.9
In recognition that appropriate insulin progression can prevent or delay type 2 diabetes–related complications and reduce unnecessary health expenditures, researchers, clinicians, and policy makers have an interest in under-standing and addressing barriers to progression among patients with type 2 diabetes. In this systematic review, we evaluate the peer-reviewed literature through July 2011 to answer 2 questions regarding insulin progression among patients with type 2 diabetes: (1) What are the patient, provider, and health system barriers to insulin progression? (2) Do insulin progression barriers differ between insulin-naive and insulin-experienced patients, and how? By enumerating the multiple sources of poten-tial barriers to insulin progression and the challenges of patients with different insulin treatment experiences, this review summarizes the best available evidence regarding obstacles to insulin progression, highlights opportunities for overcoming those barriers, and identifies knowledge gaps.
Research Design and Method
We followed PRISMA guidelines for the conduct and reporting of systematic reviews.12
Data Sources
We limited initial searches to articles published in MEDLINE, EMBASE, Science Citation Index (ISI Web of Science), PsycINFO, CINAHL, or the Cochrane Library on or before July 15, 2011. Our search strategy focused on terms related to type 2 diabetes mellitus, insu-lin, and treatment progression (eg, in Medline: [Diabetes Mellitus, Type 2[Mesh] AND “Insulin”[Mesh] AND “Therapeutics”[Mesh] AND (intens* OR escalat* OR increas* OR progres*) AND (barrier* OR obstacle* OR challeng* OR disincentiv* OR impediment* OR diffi-cult* OR limitation*)]. Search strategies specific to each database can be found in the online appendix. After eliminating duplicates across search databases, articles meeting search criteria were included in the review and were reference mined for related articles. No language restriction was imposed.
Study Selection
Final articles were included if they reported original data regarding barriers to insulin treatment progression among patients with type 2 diabetes, whether data were
Barriers to Insulin Progression
3
Polinski et al
drawn from self-report surveys, interviews, clinical tri-als, and/or observational studies. Both patient and physi-cian data were included. Articles reporting only barriers to insulin initiation were excluded, as were case studies and case series. Five reviewers (J.P., B.S., B.C., J.S., J.C.) participated in the study selection process, with at least 2 reviewers evaluating each title and abstract to identify potentially relevant articles. At least 2 reviewers then assessed complete articles for inclusion, noting 1 or more reasons for exclusion if the article was removed from consideration. Disagreement at these 2 stages of the review process was resolved by the judgment of a third reviewer (J.P., B.S., or J.C). All 5 reviewers assessed the final group of selected articles for inclusion.
Data Extraction
Two reviewers extracted data from selected articles (B.S., J.P.), including the key research questions, data sources, characteristics of the study population, study design, survey/questionnaire used or outcomes mea-sured, results, and conclusions. J.P. and B.S. evaluated the methodological quality of all cross-sectional study analyses using a 9-point, modified assessment checklist13 that assigned 1 point for each of the following: represen-tativeness of the study population (external validity); participation rate of 60% or more; description of subject attrition/data completeness; and assessment of or adjust-ment for type 2 diabetes disease duration, weight or body mass index, age, gender, insulin dose/type, and/or A1C when comparing 2 or more groups.
Results
Of 745 potentially relevant abstracts and titles screened, 73 were evaluated in full, and 10 met all inclu-sion criteria (Figure 1). Nine articles were pertinent to our goal of identifying patient, provider, and health sys-tem barriers to insulin progression: 7 articles examined patient barriers14-20 whereas 2 explored provider barri-ers.21,22 Relevant to our second question regarding whether barriers to insulin progression differed between insulin-naive and insulin-experienced patients, 6 (86%) of the 7 patient-oriented articles compared barriers to insulin treatment and/or progression between insulin-naive and insulin-experienced patients.14-16,18-20 A final article described an educational intervention to improve insulin progression by physicians.23 We failed to identify
any studies that examined health system barriers to pro-gression. Eight articles used self-reported data to identify barriers,14-21 whereas 2 articles used both self-reported and medical record data.22,23
Patient Barriers and Patient Experience With Insulin
All 7 patient-focused studies used surveys or choice instruments to elicit patients’ opinions regarding insulin progression, and many compared perceived barriers between insulin-naive versus insulin-experienced patients (Table 1). Methodological rigor across studies was gen-erally low, with 4 studies receiving a score of 3 or less on the 9-point scale, often due to lack of assessment of or control for potential confounders.
The first study ranked 274 patients’ willingness to pay for different benefits and costs associated with insulin use, including improved glucose control, weight gain, hypoglycemic episodes, and route of insulin administra-tion.15 Patients with type 2 diabetes (N = 227) were will-ing to pay the most ($114) for optimal fasting glucose control, followed by $58 for 2 kg of weight gain per year as opposed to 6 or 10 kg, and $49 for no hypoglycemic episodes. Route of insulin administration was the least
Figure 1. Study selection process.
4
Tab
le 1
Stud
ies
That
Exp
lore
Pat
ient
-Rel
ated
Bar
riers
to In
sulin
Pro
gres
sion
Auth
or (P
ublic
atio
n Ye
ar)
Rese
arch
Que
stio
nSt
udy
Popu
latio
nSt
udy
Desi
gnDa
ta T
ype
Outc
ome
mea
sure
s/qu
estio
nnai
re u
sed
Resu
ltsCo
nclu
sion
sM
etho
dolo
gica
l Qu
ality
Inde
x
Casc
iano
et a
l14
(201
1)W
hat a
re p
atie
nt
pref
eren
ces
and
perc
eptio
ns o
f di
abet
es
ther
apie
s?
▪11,
883
indi
vidu
als
with
type
2
diab
etes
dia
gnos
is, a
ge ≥
18
y▪1
8 co
untri
es in
Afri
ca, M
iddl
e Ea
st, A
sia,
Eas
tern
Eur
ope,
La
tin A
mer
ica
▪Exc
lusi
ons:
con
com
itant
pa
rtici
patio
n in
ano
ther
stu
dy,
parti
cipa
tion
in p
revi
ous
IDM
PS w
ave,
cur
rent
te
mpo
rary
insu
lin tr
eatm
ent
Cros
s-se
ctio
nal
stud
ySe
lf-re
port
data
fro
m p
atie
nts
▪IDM
PS q
uest
ionn
aire
▪Incl
uded
dire
ct a
nd in
dire
ct
disc
rete
cho
ice
scen
ario
qu
estio
ns re
quiri
ng p
atie
nts
to c
onsi
der c
riter
ia in
ord
er
to c
hoos
e be
twee
n 2
treat
men
t opt
ions
.
▪Rel
ativ
e at
tribu
te im
porta
nce
ratin
gs,
insu
lin-t
reat
ed v
s no
n-in
sulin
-tre
ated
type
2
diab
etes
pat
ient
s:▪A
dmin
istra
tion
(ora
l vs
inje
cted
): 3.
09%
vs
47.4
8% (P
< .0
001)
; tra
inin
g de
crea
sed
impo
rtanc
e of
adm
inis
tratio
n fro
m 3
3.68
% to
28
.21%
.▪P
rese
nce
of s
ide
effe
cts:
31.
59%
vs
13.7
5%
(P <
.000
1).
▪Mai
nten
ance
of b
lood
sug
ar le
vels
: 27.
80%
vs
13.0
9% (P
< .0
001)
.▪R
isk
of h
ypog
lyce
mia
: 22.
47%
vs
16.9
8%
(P <
.000
1).
▪Dos
ing:
15.
05%
vs
8.70
% (P
= .0
002)
.
▪Pat
ient
-per
ceiv
ed b
arrie
rs to
in
sulin
ther
apy
influ
ence
d by
ex
perie
nce
with
insu
lin
treat
men
t, se
lf-m
etab
olic
co
ntro
l, an
d ne
gativ
e si
de
effe
cts.
▪Pa
tient
s w
ho re
ceiv
e ty
pe 2
di
abet
es e
duca
tion
plac
e le
ss
emph
asis
on
adm
inis
tratio
n ro
ute,
sug
gest
ing
that
ed
ucat
ion
rega
rdin
g tre
atm
ent m
ay in
fluen
ce
insu
lin u
se.
2
Guim
arae
s et
al15
(2
009)
Wha
t are
pat
ient
s w
illin
g to
pay
for
insu
lin-d
eliv
ery
syst
ems,
and
w
hat a
re th
e at
tribu
tes
of
insu
lin th
erap
y th
at b
est m
eet
thei
r pr
efer
ence
s?
▪378
Can
adia
n pa
tient
s w
ith
type
1 o
r typ
e 2
diab
etes
at
Vanc
ouve
r Gen
eral
Hos
pita
l an
d St
. Pau
l’s H
ospi
tal i
n Va
ncou
ver
▪274
(72%
) sur
veys
for a
naly
sis
▪227
(83%
) with
type
2 d
iabe
tes▪
134
(49%
) ins
ulin
use
rs▪In
clus
ion:
age
≥19
y,
phys
icia
n-di
agno
sed
type
1
or ty
pe 2
dia
bete
s, u
sing
OA
Ds a
nd/o
r ins
ulin
, flu
ent i
n re
adin
g/w
ritin
g En
glis
h, a
ble
to p
rovi
de in
form
ed c
onse
nt▪E
xclu
sion
: que
stio
nnai
re
com
preh
ensi
on fa
ilure
(fa
ilure
to id
entif
y do
min
ant
treat
men
t opt
ion
in 2
fake
qu
estio
ns)
Cros
s-se
ctio
nal D
CESe
lf-re
port
ques
tionn
aire
da
ta fr
om
patie
nts
▪WTP
for d
iffer
ent a
ttrib
utes
of
insu
lin th
erap
y.▪D
iscr
eet c
hoic
e ex
perim
ent.
Ques
tionn
aire
with
15
hypo
thet
ical
cho
ice
sets
in
whi
ch p
atie
nts
mus
t ch
oose
bet
wee
n 2
treat
men
t opt
ions
. At
tribu
tes
incl
uded
:1.
FBG
con
trol:
optim
al (<
4 m
mol
/L),
subo
ptim
al (4
-7
mm
ol/L
), po
or (>
7
mm
ol/L
).2.
Hyp
ogly
cem
ic e
vent
s/m
onth
: 0, 4
, 8.
3. W
eigh
t gai
n in
firs
t yea
r: lo
w (2
kg)
, mod
erat
e (6
kg)
, hi
gh (1
0 kg
).4.
Rou
te o
f adm
inis
tratio
n fo
r ba
sal d
ose:
ora
l, su
bcut
aneo
us.
5. R
oute
of a
dmin
istra
tion
for
3× p
rand
ial d
oses
: ora
l, su
bcut
aneo
us, i
nhal
ed.
6. O
ut-o
f-po
cket
cos
ts/m
onth
: $0
, $50
, $10
0, $
200.
Type
2 D
iabe
tics
WTP
(CI)
($ C
anad
ian)
:▪O
ptim
al fa
stin
g gl
ucos
e co
ntro
l: 11
3.55
(9
8.32
-128
.78)
.▪N
o hy
pogl
ycem
ic e
vent
s/m
onth
: 48.
65
(34.
64-6
2.66
).▪2
-kg
wei
ght g
ain
in fi
rst y
ear:
58.0
7 (4
4.72
-71.
42).
▪Sub
cuta
neou
s ro
ute
for l
ong-
actin
g in
sulin
: pay
16
.17
(7.7
2-24
.62)
to a
void
it, w
here
as ty
pe 1
di
abet
es p
atie
nts
will
ing
to p
ay 1
6.02
for i
t.▪S
ubcu
tane
ous
rout
e fo
r sho
rt-ac
ting
insu
lin: p
ay
47.2
3 to
avo
id it
, whe
reas
type
1 p
atie
nts
will
ing
to p
ay 1
1.53
for i
t.In
sulin
use
rs W
TP (C
I) ($
Can
adia
n):
▪Opt
imal
fast
ing
gluc
ose
cont
rol:
146.
83
(125
.54-
168.
11).
▪No
hypo
glyc
emic
eve
nts/
mon
th: 7
5.59
(5
5.21
-95.
97).
▪2-k
g w
eigh
t gai
n in
firs
t yea
r: 70
.09
(51.
16-8
9.02
).▪S
ubcu
tane
ous
rout
e fo
r lon
g-ac
ting
insu
lin: w
illin
g to
pay
9.2
3 co
mpa
red
with
insu
lin n
aive
use
rs’
WTP
32
to a
void
it.
▪Sub
cuta
neou
s ro
ute
for s
hort-
actin
g in
sulin
: w
illin
g to
pay
0.3
6 co
mpa
red
to in
sulin
nai
ve
user
s’ W
TP 7
5 to
avo
id it
.
▪Typ
e 2
diab
etes
pat
ient
s w
illin
g to
pay
the
mos
t for
bet
ter
gluc
ose
cont
rol,
avoi
danc
e of
w
eigh
t gai
n an
d hy
pogl
ycem
ic e
vent
s.▪
Type
1 p
atie
nts
and
all i
nsul
in
user
s w
illin
g to
pay
mor
e fo
r in
crea
sed
cont
rol a
nd fe
wer
ad
vers
e ev
ents
rela
tive
to
type
2 a
nd in
sulin
nai
ve
diab
etic
s.▪F
indi
ngs
supp
ort h
ypot
hesi
s of
a
psyc
holo
gica
l bar
rier t
o in
itiat
ing
insu
lin th
erap
y, bu
t on
ce b
arrie
r has
bee
n br
oken
, di
abet
ic p
atie
nts
acce
pt
inje
ctab
le th
erap
y as
a
treat
men
t opt
ion.
3 (con
tinue
d)
5
Auth
or (P
ublic
atio
n Ye
ar)
Rese
arch
Que
stio
nSt
udy
Popu
latio
nSt
udy
Desi
gnDa
ta T
ype
Outc
ome
mea
sure
s/qu
estio
nnai
re u
sed
Resu
ltsCo
nclu
sion
sM
etho
dolo
gica
l Qu
ality
Inde
x
Mar
tinez
et a
l16
(200
7)Ho
w w
ell d
oes
the
SHIP
qu
estio
nnai
re
capt
ure
patie
nts’
m
otiv
atio
n, fe
ars,
an
d ba
rrie
rs
tow
ard
insu
lin
inje
ctio
n or
in
tens
ifyin
g in
sulin
ther
apy?
SHIP
Pre
mix
stu
dy (q
uest
ions
fo
cuse
d on
inte
nsifi
catio
n)▪1
130
patie
nts
(115
0 re
spon
dent
s)▪7
5.2%
of t
hese
are
type
2
diab
etes
pat
ient
s, tr
eate
d w
ith in
sulin
≥5
y on
ave
rage
▪Incl
usio
n: ty
pe 1
or t
ype
2 di
abet
es, t
reat
ed w
ith 2
dai
ly
inje
ctio
ns o
f pre
mix
ed in
sulin
▪Exc
lusi
on: t
ype
2 di
abet
es
treat
ed w
ith O
ADs
only,
tre
atm
ent w
ith in
sulin
oth
er
than
2 p
rem
ixed
inje
ctio
ns
Cros
s-se
ctio
nal
stud
ySe
lf-re
port
ques
tionn
aire
da
ta fr
om
patie
nts
▪SHI
P qu
estio
nnai
re (p
ilote
d):
deve
lope
d w
ith fo
cus
grou
ps o
f dia
betic
s.▪3
fiel
ds o
f ana
lysi
s on
0-1
00
scal
e: a
ccep
tanc
e an
d m
otiv
atio
n, c
onst
rain
ts a
nd
fear
s, re
stra
ints
and
ba
rrie
rs.
▪Sta
tem
ents
in “
fear
s an
d co
nstra
ints
” ca
tego
ry:
Feel
ing
rest
ricte
d be
caus
e of
sel
f-su
rvei
llanc
e;
Cons
train
t bec
ause
of d
epen
denc
y, lib
erty
loss
; Up
set d
iabe
tes
is g
ettin
g w
orse
; Fea
r of h
avin
g m
ore
hypo
glyc
emia
cris
es; F
ear t
hat t
reat
men
t ge
ts m
ore
com
plic
ated
.▪S
tate
men
ts in
“re
stra
ints
and
bar
riers
” ca
tego
ry:
Both
ered
by
bein
g se
en w
hile
inje
ctin
g in
sulin
; Fe
ar th
at p
eopl
e no
tice
I’m d
iabe
tic; B
othe
red
by s
kin
bein
g m
arke
d at
inje
ctio
n si
te; S
tress
ed
beca
use
inje
ctio
ns c
an b
e pa
infu
l.▪S
HIP
surv
ey’s
abi
lity
to p
redi
ct in
sulin
in
tens
ifica
tion
is fa
ir to
goo
d fo
r pat
ient
s al
read
y on
insu
lin: c
-sta
tistic
s 0.
65 fo
r re
stra
ints
and
bar
riers
, 0.7
8 fo
r fea
rs a
nd
cons
train
ts, 0
.86
for a
ccep
tanc
e an
d m
otiv
atio
n.▪H
ighe
r pro
porti
on o
f pat
ient
s al
read
y tre
ated
by
insu
lin in
ject
ions
und
erw
ent i
nsul
in
inte
nsifi
catio
n co
mpa
red
with
pat
ient
s or
ally
tre
ated
who
did
not
initi
ate
insu
lin in
ject
ion,
re
gard
less
the
time
of th
e st
udy.
▪57
vs 6
1 “f
ears
and
con
stra
ints
,” 2
1 vs
27
“res
train
ts a
nd b
arrie
rs”
(P <
.05)
sco
res
incr
ease
d fo
r pat
ient
s w
ho ta
lked
abo
ut in
sulin
th
erap
y w
ith th
eir p
hysi
cian
s.▪P
= .0
916
for “
acce
ptan
ce a
nd m
otiv
atio
n” s
core
di
ffere
nce
betw
een
patie
nts
who
se p
hysi
cian
s di
d or
did
not
talk
to th
em a
bout
insu
lin th
erap
y.▪7
0% v
s 37
%—
patie
nts
alre
ady
rece
ivin
g in
sulin
in
ject
ions
less
relu
ctan
t to
incr
ease
num
ber o
f in
ject
ions
vs
patie
nts
rece
ivin
g tre
atm
ent o
rally
.▪6
3% o
f pat
ient
s qu
ite m
otiv
ated
to h
ighl
y m
otiv
ated
to in
crea
se n
umbe
r of i
nsul
in
inje
ctio
ns.
▪81%
wou
ld h
ave
been
mot
ivat
ed to
incr
ease
in
sulin
ther
apy
if in
hale
d in
sulin
wer
e av
aila
ble.
▪“Ac
cept
ance
and
mot
ivat
ion”
sco
res
low
est i
n yo
ung
and
old
(<40
or >
70 y
, sco
res
of 5
9 an
d 60
, res
pect
ivel
y) (P
= .0
23).
▪“Re
stra
ints
and
bar
riers
” sc
ores
sig
nific
antly
lo
wer
in o
lder
pat
ient
s (P
< .0
001)
.▪“
Fear
s an
d co
nstra
ints
” sc
ores
—no
sig
nific
ant
diffe
renc
e by
age
.
▪Pat
ient
s al
read
y re
ceiv
ing
insu
lin h
ad fe
wer
bar
riers
to
addi
tiona
l inj
ectio
ns
com
pare
d w
ith th
ose
initi
atin
g in
sulin
; stil
l, m
any
have
co
ncer
ns a
bout
dis
ease
pr
ogre
ssio
n an
d hy
pogl
ycem
ia.
▪SHI
P co
nfirm
s im
porta
nce
of
patie
nt–p
hysi
cian
co
mm
unic
atio
n in
trea
tmen
t de
cisi
on in
dia
bete
s.
1 (con
tinue
d)
Tab
le 1
(Con
tinue
d)
6
Auth
or (P
ublic
atio
n Ye
ar)
Rese
arch
Que
stio
nSt
udy
Popu
latio
nSt
udy
Desi
gnDa
ta T
ype
Outc
ome
mea
sure
s/qu
estio
nnai
re u
sed
Resu
ltsCo
nclu
sion
sM
etho
dolo
gica
l Qu
ality
Inde
x
Peyr
ot e
t al17
(2
010)
Is q
ualit
y of
life
af
fect
ed b
y ad
ding
mea
ltim
e PR
AM o
r RAI
As
to b
asal
insu
lin
ther
apy
in
patie
nts
with
in
adeq
uate
ly
cont
rolle
d ty
pe 2
di
abet
es?
▪56
(48
com
plet
ed) t
ype
2 di
abet
es p
atie
nts
in 1
20-µ
g fix
ed-d
ose
PRAM
arm
▪56
(50
com
plet
ed) t
ype
2 di
abet
es p
atie
nts
in ti
trate
d RA
IAs
arm
▪46%
of p
atie
nts
used
insu
lin
prio
r to
stud
y▪In
clus
ion:
age
≥18
y, A
1c le
vel
>7%
, ins
ulin
-nai
ve o
r tak
ing
<50
U/d
bas
al in
sulin
for <
6 m
o, n
o pr
evio
us P
RAM
use
, 50
≥ B
MI ≥
25
kg/m
2
▪Man
y ex
clus
ions
Rand
omiz
ed c
linic
al
trial
; ope
n-la
bel,
mul
ticen
ter,
para
llel g
roup
for
24 w
k ac
ross
29
cent
ers
Self-
repo
rt qu
estio
nnai
re
data
from
pa
tient
s
▪Dia
bete
s Di
stre
ss S
cale
; av
erag
e sc
ores
acr
oss
17
item
s, e
ach
with
1
(ext
rem
ely
both
erso
me)
to
6 (n
ot a
pro
blem
) sca
le.
▪Pitt
sbur
gh S
leep
Qua
lity
Inde
x; 1
9 ite
ms,
sco
re o
f 0
(mos
t pos
itive
) to
21 (m
ost
nega
tive)
.▪D
iabe
tes
Trea
tmen
t Sa
tisfa
ctio
n Qu
estio
nnai
re
(8 it
ems,
sco
re 0
-36,
hi
gher
sco
re =
gre
ater
tre
atm
ent s
atis
fact
ion)
.▪P
RAM
-TSQ
(14
item
s, 1
-6
Like
rt-ty
pe, h
ighe
r sco
re =
hi
gh a
gree
men
t with
st
atem
ent).
▪▪A
ll as
sess
ed a
t bas
elin
e an
d w
k 24
, exc
ept P
RAM
-TSQ
(2
4 w
k on
ly).
Chan
ge in
sco
res
from
bas
elin
e to
24
wk
(inte
nsifi
catio
n st
arte
d at
4 w
k) fo
r bas
al in
sulin
+
rapi
d-ac
ting
insu
lin g
roup
—le
ast s
quar
es
mea
n ch
ange
(sta
ndar
d er
ror o
r sta
ndar
d de
via-
tion)
, P v
alue
.▪P
hysi
cian
-rel
ated
dis
tress
: –0.
20 (0
.08)
, P <
.01.
▪Reg
imen
-rel
ated
dis
tress
: –0.
29 (0
.14)
, P <
.05.
▪DTS
Q sc
ore
(trea
tmen
t sat
isfa
ctio
n): 1
0.12
(1.0
9),
P <
.001
.At
24
wk,
PRA
M-T
SQ it
ems:
mea
n (s
tand
ard
devi
atio
n), P
val
ue a
sses
sing
diff
eren
ce fr
om
scal
e m
idpo
int 3
.5.
▪Mad
e it
easi
er to
con
trol m
y w
eigh
t: 2.
83 (1
.85)
, P
< .0
5.▪M
ade
it ea
sier
to c
ontro
l my
appe
tite:
4.0
0 (1
.46)
, P
< .0
5.▪P
rovi
ded
enou
gh b
enef
it to
out
wei
gh th
e ex
tra
inje
ctio
ns: 4
.70
(1.3
8), P
< .0
01.
▪Mad
e it
easi
er to
avo
id lo
w b
lood
sug
ar re
actio
ns:
4.00
(1.4
6), P
< .0
5.▪M
ade
me
feel
mor
e co
nfid
ent a
bout
man
agin
g m
y di
abet
es: 4
.55
(1.3
0), P
< .0
01.
▪Has
sid
e ef
fect
s th
at w
ould
kee
p m
e fro
m u
sing
it
(reve
rsed
): 4.
71 (1
.53)
, P <
.001
.
Mea
ltim
e th
erap
y w
ith R
AIA
in
addi
tion
to b
asal
insu
lin w
as
asso
ciat
ed w
ith a
num
ber o
f fa
vora
ble
patie
nt-r
epor
ted
outc
omes
dur
ing
a pe
riod
of
20 w
k.
7
Snoe
k et
al18
(2
007)
How
relia
ble
and
valid
is th
e IT
AS
in m
easu
ring
the
posi
tive
and
nega
tive
appr
aisa
l of
insu
lin th
erap
y in
pe
rson
s w
ith
type
2 d
iabe
tes?
▪282
type
2 d
iabe
tes
patie
nts
(29%
resp
onse
rate
)▪1
46 in
sulin
-nai
ve▪1
36 in
sulin
-tre
ated
▪Dra
wn
from
Har
ris In
tera
ctiv
e Ch
roni
c Ill
ness
Pan
el,
>25
,000
peo
ple
with
di
abet
es in
the
US w
ho a
re
cons
ider
ed a
repr
esen
tativ
e sa
mpl
e ba
sed
on k
ey
char
acte
ristic
s fo
r thi
s po
pula
tion
Cros
s-se
ctio
nal
stud
ySe
lf-re
port
ques
tionn
aire
da
ta fr
om
patie
nts
▪ITAS
: dev
elop
ed a
nd p
ilote
d.▪5
-poi
nt L
iker
t sca
le, h
ighe
r sc
ore
= s
trong
er
agre
emen
t.▪T
o m
easu
re c
oncu
rren
t va
lidity
: WHO
-5 P
AID
Surv
ey.
▪WHO
-5 is
the
Wor
ld H
ealth
Or
gani
zatio
n -
5 sc
ale.
▪▪PAI
D: 0
-100
sco
re, h
ighe
r sc
ore
= h
ighe
r em
otio
nal
dist
ress
.▪▪W
HO-5
: 0-1
00 s
core
, hig
her
scor
e =
bet
ter e
mot
iona
l w
ell-b
eing
.
Com
parin
g in
sulin
-tre
ated
with
insu
lin-n
aive
, pr
opor
tion
who
agr
ee o
r stro
ngly
agr
ee w
ith
stat
emen
t:▪2
7% v
s 54
%: i
nsul
in s
igni
fies
failu
re w
ith
pre-
insu
lin th
erap
y.▪3
7% v
s 73
%: i
nsul
in s
igni
fies
diab
etes
has
w
orse
ned.
▪20%
vs
41%
: ins
ulin
will
mak
e ot
hers
per
ceiv
e gr
eate
r sic
knes
s.▪6
% v
s 47
%: f
ear o
f nee
dle
inje
ctio
n.▪4
0% v
s 52
%: i
nsul
in w
ill in
crea
se th
e ris
k of
hy
pogl
ycem
ia.
▪54%
vs
23%
: ins
ulin
will
cau
se w
eigh
t gai
n.▪2
8% v
s 61
%: i
nsul
in w
ill b
e de
man
ding
to
adm
inis
ter.
▪10%
vs
19%
: ins
ulin
mea
ns I
have
to g
ive
up
activ
ities
I en
joy.
▪10%
vs
23%
: inj
ectin
g in
sulin
is e
mba
rras
sing
.▪3
8% v
s 43
%: i
njec
ting
insu
lin is
pai
nful
.▪3
5% v
s 40
%: i
nsul
in m
akes
me
mor
e de
pend
ent
on m
y do
ctor
.▪A
mon
g in
sulin
-tre
ated
and
insu
lin-n
aive
pat
ient
s,
WHO
-5 s
core
indi
cativ
e of
clin
ical
dep
ress
ion
is
asso
ciat
ed w
ith s
igni
fican
tly h
ighe
r sco
re o
n IT
AS.
▪Insu
lin-t
reat
ed p
atie
nts
have
le
ss n
egat
ive
asse
ssm
ent o
f in
sulin
ther
apy
than
do
insu
lin
naiv
e pa
tient
s, s
ugge
stin
g th
at e
xper
ienc
e w
ith in
sulin
im
prov
es a
ttitu
des
abou
t us
ing
it.▪F
ear o
f ins
ulin
inje
ctio
n de
crea
ses
dram
atic
ally
with
ex
perie
nce,
but
stil
l nea
rly
40%
repo
rt in
ject
ion
as
pain
ful a
nd >
50%
ass
ocia
te
insu
lin u
se w
ith w
eigh
t gai
n.▪S
ocia
l stig
ma
is d
ram
atic
ally
re
duce
d in
insu
lin-t
reat
ed v
s in
sulin
-nai
ve, p
erha
ps d
ue to
at
titud
inal
shi
ft or
add
ition
al
expe
rienc
e.
6 (con
tinue
d)
Tab
le 1
(Con
tinue
d)
7
Auth
or (P
ublic
atio
n Ye
ar)
Rese
arch
Que
stio
nSt
udy
Popu
latio
nSt
udy
Desi
gnDa
ta T
ype
Outc
ome
mea
sure
s/qu
estio
nnai
re u
sed
Resu
ltsCo
nclu
sion
sM
etho
dolo
gica
l Qu
ality
Inde
x
Vija
n et
al19
(200
5)W
hat a
re p
atie
nts’
vi
ews
of th
e bu
rden
s of
di
abet
es th
erap
y, an
d w
hat i
s th
e im
pact
of t
hose
vi
ews
on
self-
man
age-
men
t?
▪165
3 ve
tera
ns w
ith ty
pe 2
di
abet
es (6
7% re
spon
se ra
te)
▪Rec
ruite
d fro
m 2
VA
hosp
itals
▪44%
trea
ted
with
insu
lin▪E
xclu
sion
: age
<30
y (a
ssum
ed
to h
ave
type
1 d
iabe
tes)
Cros
s-se
ctio
nal
stud
ySe
lf-re
port
ques
tionn
aire
da
ta fr
om
patie
nts
▪Aut
hor-
desi
gned
inst
rum
ent
(mai
led
surv
ey) t
o as
sess
bu
rden
s of
var
ious
hy
pogl
ycem
ic tr
eatm
ents
in
clud
ing
insu
lin.
▪7-p
oint
sca
le, h
ighe
r sco
re =
m
ore
disl
ike
of a
ctiv
ity o
r le
ss a
dher
ence
to
treat
men
t.▪O
utco
mes
ass
esse
d:
pred
icto
rs o
f dia
bete
s bu
rden
, sel
f-re
porte
d ad
here
nce
to th
erap
y, ac
cept
ance
of i
nsul
in
ther
apy
whe
n pr
escr
ibed
.
Ratin
gs o
f tre
atm
ent b
urde
n—se
lect
ed re
sults
fro
m ra
ting
with
exp
erie
nce
colu
mn
(mea
n):▪
3.1:
com
bina
tion
bedt
ime
insu
lin a
nd d
aytim
e or
al
agen
ts.
▪2.4
: ins
ulin
twic
e a
day.
▪3.
5: in
sulin
twic
e a
day
+ s
elf-
mon
itorin
g of
blo
od
gluc
ose
3× p
er d
ay.
▪4.1
: ins
ulin
3-4
× p
er d
ay.▪
Com
pare
d w
ith p
atie
nts
with
exp
erie
nce
with
all
treat
men
ts, p
atie
nts
with
out e
xper
ienc
e w
ith
the
treat
men
t per
ceiv
ed it
as
sign
ifica
ntly
mor
e bu
rden
som
e (P
< .0
01).
▪Mul
tivar
iate
ana
lyse
s: p
rior e
xper
ienc
e w
ith in
sulin
re
mai
ned
a si
gnifi
cant
pre
dict
or o
f rat
ings
of
burd
en, w
ith d
iffer
ence
s ra
ngin
g fro
m 1
.2 to
2.
8 po
ints
low
er o
n th
e 0-
6 sc
ale
(P <
.001
for
all d
iffer
ence
s).
▪Pat
ient
ratin
g of
bur
den:
onl
y si
gnifi
cant
pre
dict
or
of a
ccep
tanc
e of
insu
lin th
erap
y (o
dds
ratio
of
acce
ptan
ce =
0.5
8 pe
r 1-u
nit i
ncre
ase
in ra
ting
of b
urde
n; 9
5% C
I, 0.
48-0
.69)
.
▪In in
sulin
use
rs c
ompa
red
with
th
e in
sulin
nai
ve, t
he ra
ting
of
insu
lin b
urde
n w
as lo
wer
, but
ra
tings
stil
l inc
reas
ed
dram
atic
ally
bas
ed o
n th
e fre
quen
cy o
f inj
ectio
ns.▪
Patie
nts
are
adap
tabl
e to
new
tre
atm
ents
and
exp
erie
nce
help
s, b
ut o
nly
to a
poi
nt:
13%
refu
sed
insu
lin in
itiat
ion
beca
use
of p
erce
ived
bur
den.
5*Ad
ditio
nal
varia
bles
of
inte
rest
wer
e as
sess
ed in
the
anal
ysis
but
not
sp
ecifi
ed in
the
text
Zam
bani
ni e
t al20
(1
999)
Does
the
pres
ence
of
in
ject
ion-
rela
ted
anxi
ety
and
phob
ia in
fluen
ce
com
plia
nce,
gl
ycem
ic c
ontro
l, an
d qu
ality
of l
ife
in p
atie
nts
with
in
sulin
-tre
ated
di
abet
es?
▪115
con
secu
tive
insu
lin-t
reat
ed
diab
etic
pat
ient
s at
tend
ing
a te
achi
ng h
ospi
tal d
iabe
tes
outp
atie
nt c
linic
for r
outin
e fo
llow
-up
▪35
with
type
2 d
iabe
tes
(30%
)▪In
clus
ions
: age
>18
y, a
ble
to
give
ver
bal c
onse
nt, a
ble
to
com
plet
e qu
estio
nnai
re
unai
ded
or w
ith in
terp
rete
r▪E
xclu
sion
s: d
aily
insu
lin
inje
ctio
ns p
erfo
rmed
for <
1 m
o
Cros
s-se
ctio
nal
stud
ySe
lf-re
port
ques
tionn
aire
da
ta fr
om
patie
nts
▪IAS
and
GAS
▪For
IAS,
aut
hor-
desi
gned
in
stru
men
t der
ived
from
DS
M-IV
crit
eria
for s
peci
fic
phob
ia.
▪▪0-3
sca
le (h
ighe
r = m
ore
fear
).▪▪1
-4 s
cale
cor
resp
ondi
ng to
nu
mbe
r of s
ympt
oms
of
pani
c at
tack
.▪▪T
otal
IAS
scor
es ra
nge
from
0
to 1
4 (h
ighe
r sco
re =
mor
e fe
ar).
▪▪For
GAS
, anx
iety
sub
scal
e of
Ho
spita
l Anx
iety
and
De
pres
sion
Sca
le u
sed.
▪A1C
labo
rato
ry v
alue
m
easu
red
on d
ay o
f sur
vey.
▪14%
of t
ype
2 di
abet
es p
atie
nts
avoi
ded
inje
ctio
ns
seco
ndar
y to
anx
iety
, but
29%
trou
bled
by
the
pros
pect
of m
ore
inje
ctio
ns.
▪25
low
IAS
patie
nts
unco
ncer
ned
with
mor
e fre
quen
t inj
ectio
ns v
s 23
pat
ient
s w
ith h
igh
IAS
expr
esse
d co
ncer
n w
ith m
ore
frequ
ent
inje
ctio
ns (P
< .0
01).
▪–0.
17 (–
0.27
to –
0.07
) cor
rela
tion
betw
een
IAS
and
num
ber o
f dai
ly in
sulin
inje
ctio
ns (P
=
.001
).▪P
ropo
rtion
of p
atie
nts
avoi
ding
inje
ctio
ns in
the
high
gen
eral
anx
iety
gro
up s
igni
fican
tly g
reat
er
(28%
) com
pare
d w
ith th
e lo
w g
ener
al a
nxie
ty
grou
p (9
%) (
P <
.05)
.▪P
oiss
on re
gres
sion
ana
lysi
s: m
ean
GAS
for
inje
ctio
n av
oide
rs a
lmos
t tw
ice
that
for
nona
void
ers—
mea
n GA
S ra
tio 1
.96
(95%
CI,
1.44
-2.6
6), P
< .0
01).
▪35%
in G
AS <
8 gr
oup
and
62%
GAS
≥8
grou
p ex
pres
sed
conc
ern
at m
ore
frequ
ent i
njec
tions
(P
< .0
1).
▪Poi
sson
regr
essi
on a
naly
sis:
mea
n GA
S si
gnifi
cant
ly h
ighe
r for
pat
ient
s ex
pres
sing
co
ncer
n at
hav
ing
to in
ject
mor
e fre
quen
tly th
an
patie
nts
who
did
not
(mea
n GA
S ra
tio 1
.62
(95%
CI,
1.21
-2.1
9), P
= .0
01).
A1C
cont
rol w
as n
ot d
iffer
ent b
etw
een
high
vs
low
GA
S sc
ore
patie
nts,
nor
was
ther
e a
sign
ifica
nt
corr
elat
ion
betw
een
A1C
and
GAS.
▪App
roxi
mat
ely
one-
quar
ter o
f pa
tient
s in
this
stu
dy h
ave
a ps
ycho
logi
cal p
robl
em w
ith
inje
ctin
g in
sulin
, and
this
was
as
soci
ated
with
a h
igh
inje
ctio
n an
xiet
y or
GAS
.
3
Abbr
evia
tions
: BM
I, bo
dy m
ass
inde
x; C
I, co
nfid
ence
inte
rval
; DCE
, dis
cret
e ch
oice
exp
erim
ent;
DSM
-IV, D
iagn
ostic
and
Sta
tistic
al M
anua
l of M
enta
l Dis
orde
rs, F
ourth
Edi
tion;
DTS
Q, D
iabe
tes
Trea
tmen
t Sat
isfa
ctio
n Qu
estio
nnai
re; F
BG, f
astin
g bl
ood
gluc
ose;
GAS
, gen
eral
anx
iety
sco
re; I
AS, i
njec
tion
anxi
ety
scor
e; ID
MPS
, Int
erna
tiona
l Dia
bete
s M
anag
emen
t Pra
ctic
es S
tudy
; ITA
S, in
sulin
trea
tmen
t app
rais
al s
cale
; OAD
, ora
l an
tidia
bete
s ag
ent;
PAID
, Wel
l-bei
ng in
dex
and
Prob
lem
Are
as in
Dia
bete
s; P
RAM
, pra
mlin
tide;
PRA
M-T
SQ, P
ram
lintid
e Tr
eatm
ent S
atis
fact
ion
Ques
tionn
aire
; RAI
A, ra
pid-
actin
g in
sulin
ana
log;
SHI
P, St
udyi
ng th
e Hu
rdle
s of
Insu
lin P
resc
riptio
n; W
HO-5
, Wor
ld H
ealth
Org
aniz
atio
n -
5 sc
ale;
WTP
, will
ingn
ess
to p
ay.
Tab
le 1
(Con
tinue
d)
8
Tab
le 2
Stud
ies
That
Exp
lore
d Pr
ovid
er-R
elat
ed B
arrie
rs to
Pro
gres
sion
Auth
or (P
ublic
atio
n Ye
ar)
Rese
arch
Que
stio
nSt
udy
Popu
latio
nSt
udy
Desi
gnDa
ta T
ype
Outc
ome
Mea
sure
s/Qu
estio
nnai
res
Used
Resu
ltsCo
nclu
sion
sM
etho
dolo
gica
l Qu
ality
Inde
x
Cudd
ihy
et a
l21
(201
1)Ho
w d
o pr
imar
y ca
re
phys
icia
ns a
nd d
iabe
tes
spec
ialis
ts p
erce
ive
thei
r ro
le in
trea
ting
type
II
diab
etes
and
the
chal
leng
es o
f ins
ulin
m
anag
emen
t, pa
rticu
larly
in
sulin
inte
nsifi
catio
n?
▪Con
veni
ence
sam
ple
of 6
00
phys
icia
ns (P
CPs
and
diab
etes
sp
ecia
lists
) fro
m G
erm
any,
Japa
n,
Spai
n, T
urke
y, UK
, and
US)
▪US:
PCP
s se
eing
≥5
type
2 d
iabe
tes
patie
nts/
wee
k, s
peci
alis
ts s
eein
g ≥1
0 ty
pe 2
dia
bete
s pa
tient
s/w
eek
▪All
othe
r cou
ntrie
s: p
hysi
cian
s se
eing
≥2
type
2 d
iabe
tes
patie
nts/
wee
k▪A
ll co
untri
es: i
nsul
in p
resc
riber
s,
prac
ticin
g 3-
30 y
▪Firs
t 50
qual
ifyin
g PC
Ps a
nd 5
0 sp
ecia
lists
who
took
the
surv
ey
from
eac
h co
untr
y w
ere
incl
uded
; su
rvey
clo
sed
imm
edia
tely
afte
r co
untr
y-qu
ota
reac
hed.
▪74%
mal
e▪50
% 3
1-45
y o
ld
Cros
s- sect
iona
l st
udy
Self-
repo
rt qu
es-
tionn
aire
da
ta
from
ph
ysi-
cian
s
▪Man
agem
ent o
f Dia
bete
s in
Fut
ure
Year
s su
rvey
—ne
w 1
5-m
in
onlin
e de
scrip
tive
surv
ey o
f ins
ulin
pr
escr
iber
s (n
ot
valid
ated
)
Mai
n ba
rrie
rs to
insu
lin in
tens
ifica
tion
for t
ype
2 di
abet
es:
▪49%
: doc
tors
lack
exp
erie
nce
with
the
avai
labl
e ty
pes
of
insu
lin.
▪49%
: doc
tors
feel
that
edu
catin
g pa
tient
s ab
out i
nsul
in
inte
nsifi
catio
n w
ill ta
ke to
o m
uch
time.
▪39%
: doc
tors
do
not b
elie
ve th
at p
atie
nts
will
be
able
to
cope
with
inte
nsifi
ed in
sulin
ther
apy.
▪38%
: the
re is
a la
ck o
f gui
danc
e ab
out i
nsul
in
inte
nsifi
catio
n.▪3
8%: t
here
is a
lack
of p
atie
nt m
onito
ring
to s
how
whe
n ty
pe 2
pat
ient
s re
quire
inte
nsifi
ed th
erap
y.▪2
1%: d
octo
rs la
ck b
elie
f tha
t ins
ulin
inte
nsifi
catio
n is
ne
cess
ary.
▪10%
(US,
Spa
in, J
apan
onl
y): t
he re
imbu
rsem
ent s
ituat
ion
for i
nsul
in.
▪6%
(UK,
Ger
man
y, Tu
rkey
onl
y): s
trict
gui
delin
es.
▪16%
: the
re a
re n
o ba
rrie
rs to
insu
lin in
tens
ifica
tion
in m
y co
untr
y.▪N
early
40%
of P
CPs
and
near
ly 3
0% o
f spe
cial
ists
find
ad
min
istra
tion
of in
tens
ified
insu
lin th
erap
y di
fficu
lt.▪>
25%
bel
ieve
that
mor
e tim
e w
ith p
atie
nts,
trai
ned
nurs
es,
and
reso
urce
s to
hel
p ed
ucat
e pa
tient
s w
ould
hel
p th
em
inte
nsify
ther
apy.
▪PCP
s le
ss in
volv
ed th
an
spec
ialis
ts in
insu
lin
inte
nsifi
catio
n, d
iffer
ence
s in
bel
iefs
abo
ut w
ho is
re
spon
sibl
e fo
r in
tens
ifica
tion.
▪Mor
e ph
ysic
ian
educ
atio
n an
d tra
inin
g ne
eded
for P
CPs
(and
eve
n sp
ecia
lists
).▪A
ncill
ary
supp
ort f
rom
nur
ses,
di
etic
ians
cou
ld a
llevi
ate
time
and
effo
rt co
ncer
ns,
wor
ries
abou
t abi
litie
s of
pa
tient
s.
2
el-K
ebbi
et a
l22
(199
9)Ca
n pr
ovid
ers
accu
rate
ly
iden
tify
patie
nts
with
poo
r gl
ycem
ic c
ontro
l? W
hat
are
the
reas
ons
prov
ider
s m
ay n
ot in
tens
ify th
erap
y in
pat
ient
s w
ith p
oor
glyc
emic
con
trol?
▪5 p
hysi
cian
s an
d 8
nurs
es in
the
Grad
y M
emor
ial H
ospi
tal D
iabe
tes
Clin
ic, s
urve
yed
afte
r eac
h vi
sit
durin
g a
3-m
o pe
riod
from
5
Febr
uary
199
6 to
10
May
199
6.▪V
isit
excl
uded
if p
hysi
cian
dee
med
gl
ycem
ic g
oals
of s
tudy
in
appr
opria
te fo
r his
/her
pat
ient
s.▪A
naly
sis
rest
ricte
d to
vis
its w
here
th
ere
was
con
sens
us b
etw
een
phys
icia
n an
d nu
rse
prov
ider
on
man
agem
ent,
N =
141
6 vi
sits
for
anal
ysis
.
Cros
s- sect
iona
l st
udy
Self-
repo
rt qu
es-
tionn
aire
da
ta
from
ph
ysi-
cian
s an
d nu
rses
, el
ec-
troni
c m
edic
al
reco
rds
revi
ew
▪Aut
hor-
desi
gned
qu
estio
nnai
re:
ques
tions
rega
rdin
g gl
ycem
ic c
ontro
l, ad
vanc
emen
t of
ther
apy,
just
ifica
tion
if th
erap
y w
as n
ot
adva
nced
(bot
h di
scre
te c
hoic
e an
d op
en-e
nded
qu
estio
ns)
▪Med
ical
reco
rds
revi
ew
to c
alcu
late
rate
of
ther
apy
inte
nsifi
catio
n am
ong
rand
om
sam
ple
of p
atie
nts
durin
g th
e 3-
mo
perio
d pr
eced
ing,
du
ring,
and
afte
r the
qu
estio
nnai
re w
as
adm
inis
tere
d
▪85%
nur
ses
vs 2
1% p
hysi
cian
s fa
vore
d hi
gher
targ
et g
oals
du
e to
pat
ient
s’ p
oor c
ompl
ianc
e (2
6%),
chro
nic
illne
ss
(18%
), ol
der a
ge (1
6%),
adva
nced
dia
bete
s co
mpl
icat
ions
(1
2%),
conc
ern
abou
t hyp
ogly
cem
ia (6
%).
▪88%
wel
l-con
trolle
d pa
tient
s co
rrec
tly id
entif
ied,
94%
of
poor
ly c
ontro
lled
patie
nts
corr
ectly
iden
tifie
d ba
sed
on
treat
men
t gui
delin
es.
▪Rea
sons
for n
ot in
tens
ifyin
g tre
atm
ent i
n po
orly
con
trolle
d,
not i
nten
sifie
d gr
oup:
34%
, con
trol i
s im
prov
ing;
16%
, pa
tient
is n
onco
mpl
iant
with
med
icat
ions
; 10%
, die
t no
ncom
plia
nce;
8%
, acu
te il
lnes
s; 7
%, p
atie
nt re
fusa
l; 3%
, hyp
ogly
cem
ia; 4
%, o
ther
; 18%
, no
reas
on.
▪55%
poo
rly c
ontro
lled
patie
nts
inte
nsifi
ed b
efor
e th
e qu
estio
nnai
re, 6
4% d
urin
g qu
estio
nnai
re p
erio
d, 6
3%
post
ques
tionn
aire
per
iod.
▪20%
man
agin
g hy
perg
lyce
mia
with
die
t alo
ne, 4
0% w
ith
sulfo
nylu
reas
, 30%
with
insu
lin, 1
0% w
ith in
sulin
+
sulfo
nylu
reas
.▪T
hera
py m
ost l
ikel
y to
be
inte
nsifi
ed in
pat
ient
s ta
king
in
sulin
vs
diet
alo
ne (P
< .0
1).
▪Pro
vide
rs h
ad a
ccur
ate
perc
eptio
ns o
f pat
ient
s’
glyc
emic
con
trol a
nd
legi
timat
e ju
stifi
catio
ns fo
r no
t int
ensi
fyin
g th
erap
y.▪In
28%
of p
oorly
con
trolle
d pa
tient
s, th
erap
y w
as n
ot
adva
nced
due
to
nona
dher
ence
to m
eal p
lan
or u
nsta
ted
reas
on.
▪Nur
ses
wer
e m
ore
likel
y to
ch
oose
hig
her g
lyce
mic
go
als
for p
atie
nts.
▪Doc
tors
mor
e lik
ely
to c
hoos
e ph
arm
acol
ogic
al tr
eatm
ent;
nurs
es d
iet.
▪Inte
nsifi
catio
n in
crea
sed
sign
ifica
ntly
dur
ing
the
ques
tionn
aire
per
iod:
Ha
wth
orne
effe
ct.
3
Abbr
evia
tion:
PCP
, prim
ary
care
phy
sici
an.
9
Tab
le 3
An In
terv
entio
n to
Add
ress
Bar
riers
888
Auth
or
(Pub
licat
ion
Year
)Re
sear
ch Q
uest
ion
Stud
y Po
pula
tion
Stud
y De
sign
Data
Typ
eOu
tcom
e M
easu
res/
Ques
tionn
aire
s Us
edRe
sults
Conc
lusi
ons
Met
hodo
logi
cal
Qual
ity In
dex
Ena
et a
l23 (2
009)
How
wer
e pr
escr
ibin
g ha
bits
and
glu
cose
co
ntro
l affe
cted
by
the
impl
emen
tatio
n of
an
educ
atio
nal
stra
tegy
for
inpa
tient
s in
m
edic
al w
ards
?
▪33
inte
rnal
med
icin
e an
d em
erge
ncy
room
phy
sici
ans
surv
eyed
(46%
re
spon
se ra
te)
▪Pat
ient
s di
scha
rged
from
the
inte
rnal
m
edic
ine
depa
rtmen
t of H
ospi
tal
Mar
ina
Baix
a (S
pain
), 46
in e
ach
perio
d: b
efor
e th
e in
terv
entio
n, 3
m
o po
st in
terv
entio
n, a
nd 9
mo
post
in
terv
entio
n—13
8 pa
tient
s to
tal
▪Pat
ient
incl
usio
n cr
iteria
: >18
y o
ld,
type
2 d
iabe
tes
or g
lyce
mia
(>20
0 m
g/dL
), ho
spita
lizat
ion
for ≥
72 h
▪Pat
ient
exc
lusi
on c
riter
ia: t
ype
1 di
abet
es, p
regn
ancy
, hyp
ogly
cem
ia
(<60
mg/
dL),
diab
etic
ket
oaci
dosi
s,
hype
rgly
cem
ic h
yper
osm
olar
sy
ndro
me
▪Qua
si-e
xper
imen
tal
befo
re a
nd a
fter
educ
atio
n in
terv
entio
n st
udy.
▪Inte
rven
tion
is a
20
-min
fa
ce-t
o-fa
ce
educ
atio
nal
sem
inar
, poc
ket
guid
es a
nd p
oste
rs
dist
ribut
ed to
ph
ysic
ians
.
▪Qua
si-
expe
rimen
tal:
patie
nt
disc
harg
e re
cord
s.
▪Inte
rven
tion
surv
ey:
self-
repo
rt qu
estio
nnai
re
data
from
ph
ysic
ian.
▪Aut
hor-
desi
gned
inst
rum
ent
(que
stio
nnai
re) a
sses
sing
pr
ovid
er a
ttitu
des,
fa
cilit
ator
s, a
nd b
arrie
rs
rega
rdin
g us
e of
ba
sal-b
olus
insu
lin th
erap
y (5
-poi
nt L
iker
t sca
le).
▪Fro
m p
atie
nts’
med
ical
reco
rd:
inpa
tient
dia
bete
s th
erap
y ad
min
iste
red
(adh
eren
ce to
pr
actic
e re
com
men
datio
ns),
glyc
emic
con
trol,
insu
lin
dose
, pro
porti
on o
f pat
ient
s w
ith in
sulin
inte
nsifi
catio
n at
dis
char
ge.
▪17%
pat
ient
s tre
ated
with
bas
al-b
olus
co
rrec
tion
dose
bef
ore
inte
rven
tion;
85%
at
3 m
o po
st in
terv
entio
n; 9
3% a
t 9 m
o po
st
inte
rven
tion.
▪Bas
al-b
olus
-cor
rect
ion
insu
lin d
osag
e w
as
asso
ciat
ed w
ith a
n in
crea
se in
the
tota
l am
ount
of i
nsul
in a
dmin
iste
red
per d
ay.
▪20%
of p
atie
nts
with
A1C
>7%
at d
isch
arge
le
ft w
ith in
tens
ified
insu
lin th
erap
y in
pr
eint
erve
ntio
n pe
riod;
50%
at 3
mo
post
; 25
% a
t 9 m
o po
st in
terv
entio
n.▪U
se o
f ora
l ant
idia
betic
age
nts
decr
ease
d fro
m
44%
of p
atie
nts
in th
e pr
eint
erve
ntio
n pe
riod
to 9
% a
t 3 m
o po
st a
nd 4
% a
t 9 m
o po
st in
terv
entio
n.Ph
ysic
ian
surv
ey, n
o ef
fect
mea
sure
m
odifi
catio
n by
age
:▪M
edia
n 5;
IQR,
5-5
: will
ingn
ess
to u
se in
sulin
as
bas
al-b
olus
-cor
rect
ion
dosa
ge.
▪Med
ian
4; IQ
R, 4
-5: p
erce
ptio
n of
bet
ter
glyc
emic
con
trol w
ith b
asal
-bol
us c
orre
ctio
n in
sulin
dos
age
.▪Med
ian
4; IQ
R, 2
.5-4
: con
cern
s ab
out t
he
grea
ter r
isk
of h
ypog
lyce
mia
with
ba
sal-b
olus
cor
rect
ion
insu
lin d
osag
e.▪
Med
ian
3; IQ
R, 2
-4: s
impl
icity
of t
he p
ropo
sed
insu
lin a
lgor
ithm
as
basa
l-bol
us-c
orre
ctio
n.▪M
edia
n 5;
IQR,
4-5
: use
fuln
ess
of p
ocke
t gu
ides
and
pos
ter d
ispl
ays.
▪Sta
ndar
dize
d ed
ucat
iona
l ap
proa
ch a
ddre
ssed
to
phy
sici
ans
and
nurs
es in
inte
rnal
m
edic
ine
and
emer
genc
y w
ards
was
sa
fely
ass
ocia
ted
with
a
bette
r adh
eren
ce to
st
anda
rds
and
low
er
glyc
emia
in
hosp
italiz
ed p
atie
nts
with
dia
bete
s.▪
Impa
ct w
as n
ot
sust
aine
d: re
gres
sion
to
pre
inte
rven
tion
valu
es
at 9
mo—
Haw
thor
ne
effe
ct?
▪Con
cern
abo
ut s
impl
icity
of
dos
ing
algo
rithm
, ev
en a
fter e
duca
tiona
l in
terv
entio
n.
Cros
s-se
ctio
nal
inte
rven
tion
surv
ey: 2
(p
atie
nt d
ata
not
asse
ssed
).
Abbr
evia
tion:
IQR,
inte
rqua
rtile
rang
e.
The Diabetes EDUCATOR
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important attribute in a regimen for both insulin-naive and insulin-experienced patients, but experience with insulin mattered: Experienced insulin users were willing to pay only up to $9 to avoid injecting insulin, whereas insulin-naive patients were willing to pay up to $75. These data suggest that once patients were familiar with insulin injection, its importance as a barrier to treatment and insulin progression was minimized.
Injection experience was also important in a survey of 11,883 patients with type 2 diabetes: Only 3% of insulin-experienced patients ranked administration route (oral vs injected) as the most important attribute of a treatment regimen.14 Patients who had received diabetes training placed less importance on administration route than those who had not, 28% versus 34% (P < .0001). The presence of side effects (32% vs 14%), maintenance of blood sugar levels (28% vs 13%), and avoidance of hypoglycemia (22% vs 17%) were more important attri-butes for insulin-treated patients than for insulin-naive patients. In a validation study for a new insulin treatment appraisal scale (ITAS), insulin experience was again associated with more favorable appraisals of insulin among 282 patients with type 2 diabetes.18 When insulin-treated patients were compared with insulin-naive patients, fewer believed that insulin was demanding to administer (28% vs 61%) or that insulin would make oth-ers perceive greater sickness (20% vs 41%). However, more agreed that insulin use would cause weight gain (54% vs 23%). Although fear of needle injection was dramatically lower (6% vs 47%), 38% of insulin-treated patients still agreed that injection was painful.
Among 1653 veterans responding to a survey, insulin experience was associated with lower perceived treat-ment burden by 1.2 to 2.8 points on a 7-point scale.19 In a multivariate analysis of adherence to therapy, the veter-ans’ ratings of burden were the only significant predictor of adherence to insulin and of willingness to accept insu-lin therapy. One study occurred in the context of an open-label randomized controlled trial.17 Among 50 patients randomized to receive basal insulin plus a rapid-acting insulin analog for 20 weeks, patients reported on a 6-point scale (with higher ratings indicating more favor-able opinion) that the regimen made it harder to control their weight (mean score = 2.83 ± 1.85). That said, these same patients agreed that the regimen’s overall benefit outweighed the need to administer additional injections (mean score = 4.70 ± 1.38), made it easier to avoid hypo-glycemia (mean score = 4.00 ± 1.46), and made it easier
to control appetite (mean score = 4.00 ± 1.46). The study also compared the new regimen to a basal insulin plus pramlintide regimen, but the follow-up periods on treat-ment were unequal, making the comparison between regimens invalid.
Two studies did not break out results by diabetes type. A questionnaire validation study found that 70% of insulin-treated patients versus 30% of insulin-naive patients were willing to increase the frequency of insulin injection.16 In a study that explored injection-related anxiety among 80 patients with type 1 and 35 with type 2 diabetes, nearly 30% of patients injecting insulin reported being troubled by the prospect of additional injections, and 14% reported avoiding injections alto-gether.20 There was a slight negative correlation between number of daily injections and insulin anxiety score, –0.17 (95% confidence interval, –0.27 to –0.07). Patients with high insulin anxiety scores also reported high gen-eralized anxiety scores; however, generalized anxiety score was not associated with A1C control.
Provider Barriers
A cross-sectional study performed in an outpatient clinic surveyed 5 physicians and 8 nurses regarding their treatment progression decisions during 1416 patient vis-its for type 2 diabetes (Table 2).22 Although study results described barriers to any diabetes treatment progression, 40% of patients were already taking insulin. When pro-viders could not agree on a treatment plan, physicians more often endorsed progression whereas nurses favored delayed action due to perceptions of glycemic control or patient noncompliance. Among 146 patients with poor glycemic control whose treatment was not progressed, providers most often reported that control was improving (34%), patients were noncompliant with medications (16%) or diet (10%), or there was an acute intervening illness (8%), or provided no reason (18%).
In a second study, a Web-based survey was adminis-tered to 600 physicians across 6 countries to explore barriers to insulin progression.21 Nearly 40% of primary care physicians and 30% of specialists found administra-tion of progressed insulin therapy difficult and wanted more support staff and resources to assist them. About one-half (49%) reported that doctors lack experience with available types of insulin and that educating patients regarding progression would take too much time. Almost 40% agreed that patients cannot cope with progressed
Barriers to Insulin Progression
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Polinski et al
regimens, there is a lack of guidance about insulin pro-gression, and there is a lack of patient monitoring to show when patients with type 2 diabetes require progres-sion. In the United Kingdom, Germany, and Turkey, 6% cited strict national guidelines as barriers to progression. In the United States, Spain, and Japan, 10% cited reim-bursement difficulties as a barrier. Both provider-focused studies had poor methodological quality, with scores of 322 and 2,21 respectively, on the 9-point scale.
An Intervention to Address Barriers
In an inpatient setting, 33 physicians (representing a 46% response) responded to a survey regarding inpatient insulin use after they attended a 20-minute educational lecture to introduce and promote the use of a new stan-dardized basal-bolus treatment protocol in place of a sliding scale approach (Table 3).23 On a 5-point Likert scale, physicians indicated great willingness to prescribe the new basal-bolus therapy (median [interquartile range] = 5 [5-5]). Most (4 [4-5]) agreed that standardized basal-bolus insulin therapy would provide better control than the former sliding scale protocol, but most also had con-cerns about a greater risk of hypoglycemia (4 [2.5-5]). Providers were divided about the simplicity of adminis-tering the new protocol (3 [2-4]) but did adopt it. Patient discharge records showed that 17% of inpatients were treated with basal-bolus therapy before the educational intervention, 85% at 3 months post intervention, and 93% at 9 months post intervention.
Conclusions
This systematic review identified 10 studies that examined barriers to insulin progression. Many com-pared barriers to insulin use among insulin-naive versus insulin-experienced patients. Studies that examined patient barriers to progression were most common, fol-lowed by 2 studies of provider barriers and 1 study describing an educational intervention to improve pro-gression rates. Overall, both patient and provider experi-ence with insulin and education about progression appeared to mitigate barriers to progression. However, the small number of studies available, along with existing studies’ methodological limitations, narrow focus on only a few potential barriers, and grouping of patients with type 1 and type 2 diabetes, makes a comprehensive assessment of barriers to insulin progression difficult.
Of the 7 studies describing patient barriers to insulin progression, 6 compared the perceptions and beliefs of insulin-treated patients with insulin-naive patients. Across all 6 studies, injection-related concerns were less prominent and perceptions of insulin progression and burden of insulin therapy were more favorable among insulin-treated versus insulin-naive patients.18,19 Insulin-treated patients were less likely to believe that insulin was hard to administer, injection was painful, progres-sion would limit their daily activities, or progression would result in greater perceptions of sickness by oth-ers.18 As compared with insulin-naive patients, insulin-treated patients were more concerned with side effects, glycemic control, weight gain, and hypoglycemic events than with the need for injections.14 These results suggest that experience with insulin and/or diabetes education can minimize barriers to insulin progression, and the results highlight the potential of educational interven-tions to address injection and burden of disease-related barriers. Indeed, one study found that lower perceived burden of treatment regimen was the only consistent pre-dictor of willingness to progress and of adherence to progressed treatment,19 and the authors suggested that barriers to treatment progression might be reduced if patients were offered insulin as a “temporary trial.” This approach allows patients to gain experience and reassess their perceptions of insulin therapy but relieves the pres-sure of all-or-nothing long-term use.
However, even patients’ experience and education did not eliminate all barriers evaluated. Nearly 40% of insulin-treated patients still reported that injection was painful18 and 30% expressed concern about the need for additional injections.20 Insulin-treated patients also reported weight gain concerns.14,17,18 Engaging patients in a shared decision-making process24 to compare the benefits of treat-ment with potential drawbacks may improve patients’ willingness to progress their therapy and their adherence to it. In one study, patients agreed that the progressed regimen “provided enough benefit to outweigh the extra injections.”17 For the most part, the patient-focused studies examined barriers that have previously been identified as important predictors of insulin initiation and assessed their presence in the context of insulin progression. Few studies examined barriers that might be progression-specific, leav-ing a gap in our understanding of barriers that might be unique to insulin progression.
Provider-related barriers to insulin progression often derived from providers’ concerns about their patients’
The Diabetes EDUCATOR
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abilities or willingness to adopt a progressed regimen. Barriers cited by providers in 2 studies included patients’ noncompliance with the existing pharmacological treat-ment regimen or diet,22 patients’ inability to cope with a progressed regimen,21 and lack of time to educate patients about progression.21 Physicians also described their own lack of experience with and knowledge of types of insulin and progression protocols,21 even those who had just participated in an educational intervention to improve progression rates in the inpatient setting.23 However, the proportion of patients in whom insulin therapy was progressed was increased following the edu-cational intervention, suggesting that education repre-sents an opportunity to reduce barriers to progression.
A full exploration of barriers to insulin progression was limited by the cross-sectional design of the available studies, generally low methodological quality, and nar-row focus. Included studies largely relied on self-reported data assessed at a single point in time, so that they did not evaluate which barriers affected subsequent progression of therapy or the occurrence of health out-comes related to diabetes. Although 2 provider-based studies supplemented their cross-sectional data with prospective or retrospective assessment of insulin pro-gression over time, none accounted for time-varying fac-tors that might confound the association between intervention/survey and progression, nor did they quan-tify the association between barriers and progression.22,23 In their analyses, only 2 studies controlled for factors that might confound exposure-outcome associations.19,23 Few studies examined social stigma, access to pharmacies, or adherence to progressed therapy. Several studies failed to distinguish between patients with type 1 and type 2 dia-betes or between patients who progressed to more fre-quent insulin administration versus those who progressed to other therapies.16,19,20 Despite our extensive search, we found no studies that examined health system–based bar-riers, nor did we find any studies that examined patient, provider, and health system barriers concurrently to explore their impact on the likelihood of insulin progres-sion. Because treatment decisions involve all 3 levels of influence, such comprehensive studies are needed.
This systematic review suggests that both patients and physicians who have experience with insulin or who have received diabetes or insulin-specific education have fewer barriers to insulin progression compared with those who are insulin-naive. Interventions that introduce patients and physicians to insulin use and/or educate them about it may
be effective in reducing barriers that can impede insulin progression, such as injection-related aversion, perceived burden of disease, and perceived inability of patients to handle progressed regimens. However, studies in large part failed to identify novel barriers that might additionally explain incomplete application of insulin progression where indicated. Novel barriers such as cost, access, social stigma, social support, and health system–based factors must be proposed and studied among insulin-experienced patients whose disease status merits progression. Cross-sectional data need to be supplemented with longitudinal data, and investigators need to use study designs that address confounding factors and the clustering of patients within providers and within health care environments. The most helpful future studies will be both multifactorial and longitudinal in nature, examining the relative contributions of patient, provider, and health system factors on progres-sion rates and type 2 diabetes–related health outcomes. At present, enhanced education is a promising strategy, and future studies will both furnish researchers and clinicians with improved data to develop educational interventions and provide guidance on additional efforts that may be needed.
Implications/Relevance for Diabetes Educators
• Interventions that introduce patients and physicians to insu-lin use and/or educate them about it may be effective in reducing barriers that can impede insulin progression, such as injection-related aversion, perceived burden of disease, and perceived inability of patients to handle progressed regimens. Therefore, enhanced education for patients and providers is a promising strategy to improve insulin progres-sion rates.
• Longitudinal data are needed to study the link between bar-riers to insulin progression and A1C and health outcomes.
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