Effective interventions to improve medication adherence in ... · disease characteristics, intra- and inter-personal factors, and environmental characteristics [1]. Patients, providers

part of

29ISSN 1758-190710.2217/DMT.13.62 © 2014 Future Medicine Ltd Diabetes Manage. (2014) 4(1), 29–48Diabetes Manage.

Summary Aim: Medication adherence is associated with improved outcomes in diabetes. Interventions have been established to help improve medication adherence; however, the most effective interventions in patients with Type 2 diabetes remain unclear. The goal of this study was to distinguish whether interventions were effective and identify areas for future research. Methods: Medline was searched for articles published between January 2000 and May 2013, and a reproducible strategy was used. Study eligibility criteria

1Center for Health Disparities Research, Medical University of South Carolina, Charleston, SC, USA 2Division of General Internal Medicine & Geriatrics, Department of Medicine, Medical University of South Carolina, Charleston, SC, USA 3Center for Disease Prevention & Health Interventions for Diverse Populations, Charleston VA, REAP, Ralph H Johnson VAMC,

Charleston, SC, USA

*Author for correspondence: Tel.: +1 843 876 2969; Fax: +1 843 876 1201; [email protected]

Medication adherence is an important element in diabetes management, but may not be solely responsible for achieving glycemic control.

Three critical components of any intervention are education, skills training and problem-solving. Most of the interventions in this review focused on education rather than the other components. Based on this finding, more research is needed to identify effective interventions for improving medication adherence in Type 2 diabetes. Interventions targeting diabetes self-management are needed and must be developed.

One-on-one counseling was the method used in many of the randomized controlled trials reviewed, and was found to be effective.

Interventions led by pharmacists demonstrated the most statistically significant results. Although small in number, interventions using other types of facilitators such as nurse educators, community health workers and certified diabetes educators were also effective.

Uniform definitions for medication adherence must be constructed.

Interventions should be simple and tailored to patients’ individual needs to increase the likelihood of effectiveness and improved outcomes.

Clinical outcomes may not adequately reflect medication adherence.

Benefits of medication adherence must continue to be reinforced.

Prac

tice

Poi

nts

Effective interventions to improve medication adherence in Type 2 diabetes: a systematic review

Review

Joni L Strom Williams1,2, Rebekah J Walker1,3, Brittany L Smalls1,2, Jennifer A Campbell1,2 & Leonard E Egede*1,2,3

Diabetes Manage. (2014) 4(1) future science group30

review Williams, Walker, Smalls, Campbell & Egede

Medication adherence is one of several behaviors vital to diabetes self-management and clinical outcomes. The variables believed to contribute to adherence behaviors include treatment and disease characteristics, intra- and inter-personal factors, and environmental characteristics [1]. Patients, providers and health systems, in addi-tion to the treatment plan itself, may contribute to the success of adherence [2,3].

Adherence has been associated with better glycemic control, fewer diabetes-related com-plications, reduced hospitalizations, reduced healthcare costs, and lower all-cause mortality [4–8]. Despite the known benefits of medica-tion adherence in patients with Type 2 dia-betes mellitus (T2DM), adherence rates vary, with patients taking between 36 and 93%

of prescribed recommended doses [4]. Addi-tionally, national clinical practice guidelines emphasize the need for composite control of blood glucose, blood pressure and choles-terol to improve glycemic control and reduce adverse outcomes, but only 43, 29 and 52% of patients with T2DM have controlled blood sugar (HbA1c ≥7%), blood pressure (systolic blood pressure

Interventions to improve medication adherence in Type 2 diabetes review

future science group www.futuremedicine.com 31

Given the complex assignment of role responsibility in medication adherence and the variety of methods used to determine adherence to medication regimens, we aimed to identify interventions targeted at improving medication adherence and T2DM-related clinical outcomes in adults. The goal of this systematic review was to distinguish whether interventions were effective and identify areas for future research.

Methods information sources, eligibility criteria

& searchA reproducible strategy was used to identify interventions addressing medication adherence in patients with T2DM. Studies were identified by searching Medline on 23 May 2013 for arti-cles published in the English language between 2000 and 2013. The search terms were based on the Cochrane Metabolic and Endocrine Dis-order Group search strategy for T2DM [13] and the Cochrane search strategy for medication compliance/adherence [14]. Some search terms in the Cochrane strategies were not used based on the goals of this review. The search strategy is given in Box 1.

Study selection & data collectionEligibility assessment was performed by four independent authors (JLS Williams, RJ Walker, BL Smalls and JA Campbell) in a standardized manner and disagreements were resolved by the fifth author (LE Egede). The process used to identify eligible citations is shown in Figure 1. Titles and abstracts were reviewed using a stan-dardized checklist. Abstracts were eliminated if

they did not investigate a T2DM patient popu-lation, measure medication adherence/compli-ance as an outcome or describe an intervention. Interventions included randomized controlled trials (RCTs) and quasiexperimental studies, with and without a control arm.

Data collected from the eligible articles are shown in Tables 1–4. For each study, data were extracted on the number of participants, sam-ple population, duration of intervention, set-ting of intervention, study design and type of control (Table 1). An outcome table for medica-tion adherence was created to include the mean baseline medication adherence score, mean change (or baseline and postintervention if not reported) and statistical significance (Table 2). Table 2 also reports the method used to mea-sure medication adherence, categorized as phar-macy claims, electronic monitoring, pill count, self-report or serum/blood levels. If the article measured HbA1c, it was included in Table 3, which provides mean baseline HbA1c, mean change (or baseline and postintervention if not reported) and statistical significance. Each article was analyzed for relevant intervention characteristics, including whether it was cul-turally tailored, educational or skills focused, device driven (i.e., mobile phone, computers with internet access or landline telephone) and/or personnel administered (i.e., commu-nity health worker [CHW] or pharmacist) (Table 4). A narrative review was performed as the heterogeneous measures used to determine medication adherence precluded conducting a meta-ana lysis. Although risks of bias exist, articles were not excluded due to the limited

148,990 articles identi�edfor diabetes

228,716 articles identi�edfor compliance/adherence

311,657 articles identi�edfor intervention

922 articles screened afterduplicates were removed

56 full articles reviewed

27 eligible studies includedin the systematic review

Eliminated 866 ineligibleabstracts

Eliminated 29 ineligiblearticles

Figure 1. Process for eligible article selection.


review Williams, Walker, Smalls, Campbell & EgedeTa

ble

1. S

tudi

es m

eeti

ng in

clus

ion

crite

ria.

Stud

y (y

ear)

Pati

ents

(n)

Sam

ple

popu

lati

onD

urat

ion

Sett

ing

inte

rven

tion

des

crip

tion

Stud

y de

sign

Type

of c

ontr

olRe

f.

Al M

azro

ui

et al.

(200

9)24

0A

dults

with

T2D

M12

mon

ths

Mili

tary

hos

pita

l ou

tpat

ient

clin

ic

in th

e U

nite

d A

rab

Emira

tes

Patie

nts

rece

ived

edu

catio

n ab

out t

heir

illne

ss

from

a re

sear

ch p

harm

acis

t tha

t inc

lude

d co

mpl

icat

ions

, pro

per m

edic

atio

n do

sage

and

st

orag

e, a

s w

ell a

s a

heal

thy

lifes

tyle

RCT

Stan

dard

pr

ovid

er c

are

and

nonc

onta

ct

cont

rol g

roup

[15]

Aro

ra et a

l. (2

012)

23

Adu

lts w

ith T

2DM

3 w

eeks

Emer

genc

y de

part

men

t at L

os

Ang

eles

Cou

nty

Hos

pita

l (CA

, USA

)

Part

icip

ants

rece

ived

dai

ly te

xt m

essa

ges

with

he

alth

info

rmat

ion

incl

udin

g kn

owle

dge,

he

alth

y ea

ting,

exe

rcis

e, s

elf-

effica

cy a

nd

med

icat

ion

adhe

renc

e

Pre–

post

-tes

t N

one

[16]

Baba

mot

o et al.

(200

9)31

8H

ispa

nic/

Latin

os n

ewly

di

agno

sed

with

T2D

M6

mon

ths

Inne

r-ci

ty fa

mily

he

alth

cen

ter i

n Lo

s A

ngel

es (C

A, U

SA)

Dia

bete

s ed

ucat

ion

and

mon

itorin

g se

rvic

es

inco

rpor

atin

g pa

rtic

ipan

t pre

fere

nces

usi

ng

CHW

s or

CM

s

Pre–

post

-tes

t St

anda

rd

prov

ider

car

e an

d no

ncon

tact

co

ntro

l gro

up

[17]

Bogn

er et a

l. (2

010)

58A

fric

an–A

mer

ican

adu

lts

aged

50+

yea

rs w

ith

HbA

1c >

7 an

d di

agno

sis

of

depr

essi

on

4 w

eeks

Com

mun

ity-

base

d pr

imar

y ca

re p

ract

ice

in P

hila

delp

hia

(PA

, U

SA)

An

inte

grat

ed C

M w

orke

d w

ith p

atie

nt

and

prov

ider

to p

rovi

de e

duca

tion

abou

t de

pres

sion

and

dia

bete

s

RCT

Usu

al c

are

[18]

Bogn

er et a

l. (2

012)

180

Indi

vidu

als

with

T2D

M

≥30

year

s w

ith d

iagn

osis

of

dep

ress

ion

2-w

eek

run-

in,

3 m

onth

s

Prim

ary

care

pra

ctic

es

in P

hila

delp

hia

(PA

, U

SA)

Run-

in p

hase

and

inte

rven

tion

phas

e. In

tegr

ated

CM

wor

ked

with

pat

ient

and

pro

vide

r to

prov

ide

educ

atio

n ab

out d

epre

ssio

n an

d T2

DM

RCT

Usu

al c

are

[19]

Bren

nan

et al.

(201

2)In

terv

entio

n:

5123

Cont

rol:

24,1

24

Empl

oyee

s with

T2D

M

wor

king

in a

hea

vy

indu

stry

com

pany

in

the

mid

wes

t whe

re

CVS

Care

mar

k w

as th

e ph

arm

acy

bene

fit m

anag

er

18 m

onth

s12

CVS

reta

il ph

arm

acie

s in

no

rthw

est I

ndia

na

(USA

)

Ther

e w

ere

two

inte

rven

tion

grou

ps (r

etai

l an

d ph

arm

acy

bene

fit m

anag

emen

t)

and

four

inte

rven

tion

prog

ram

s: g

ener

al

info

rmat

ion;

initi

atio

n of

ACE

inhi

bito

rs a

nd/o

r st

atin

s; ad

here

nce

enfo

rcem

ent;

and

first

-fill

coun

selin

g

Pros

pect

ive

coho

rtU

sual

car

e[20]

Cast

illo et al.

(201

0)70

enr

olle

d an

d 47

co

mpl

eted

pr

e–po

st-

test

dat

a

His

pani

c/La

tino

resi

dent

s w

ith T

2DM

10 w

eeks

Com

mun

ity

self-

care

(n

oncl

inic

al) c

ente

rsCH

Ws

cond

ucte

d 2-

h T2

DM

edu

catio

n se

ssio

ns

addr

essi

ng s

elf-

man

agem

ent

Pre–

post

-tes

t de

sign

N/A

[21]

Chan

et a

l. (2

011)

105

Adu

lts w

ith a

t le

ast 5

dru

gs a

nd

HbA

1c ≥

8

9 m

onth

sPu

blic

hos

pita

l in

Hon

g Ko

ngSt

ruct

ured

pha

rmac

ist c

are

prog

ram

pro

vidi

ng

15–3

0 m

in w

ith p

harm

acis

t bef

ore

each

ph

ysic

ian

visi

t

RCT

Usu

al c

are

[22]

Farm

er et a

l. (2

012)

211

Indi

vidu

als

with

T2D

M

and

HbA

1c v

alue

≥7.

5%,

and

pres

crib

ed a

t lea

st

one

gluc

ose-

low

erin

g or

al

med

icat

ion

12 w

eeks

13 p

rimar

y ca

re

prac

tices

in

Oxf

ords

hire

, Bu

ckin

gham

shire

, Su

ffolk

, Ess

ex a

nd

Hun

tingd

onsh

ire

(UK)

Patie

nts

wer

e as

ked

ques

tions

abo

ut th

eir

belie

fs re

gard

ing

taki

ng m

edic

atio

n re

gula

rly,

posi

tive

beha

vior

s w

ere

rein

forc

ed a

nd

prob

lem

-sol

ving

was

use

d fo

r neg

ativ

e be

liefs

. Pat

ient

s w

ere

aske

d to

writ

e th

e ex

act

circ

umst

ance

s in

whi

ch th

ey w

ould

take

thei

r m

edic

atio

n

RCT

Usu

al c

are

[23]

BGSM

: Blo

od g

luco

se m

onito

ring;

CH

W: C

omm

unit

y he

alth

wor

ker;

CM

: Cas

e m

anag

er; D

MSM

: Dia

bet

es m

ellit

us s

elf-

man

agem

ent;

N/A

: Not

app

licab

le; R

CT:

Ran

dom

ized

con

trol

led

tria

l; T1

DM

: Typ

e 1

diab

etes

mel

litus

; T2

DM

: Typ

e 2

diab

etes

mel

litus

; TO

FHLA

: Tes

t of F

unct

iona

l Hea

lth L

itera

cy in

Adu

lts.



Tabl

e 1.

Stu

dies

mee

ting

incl

usio

n cr

iteri

a (c

ont.)

.

Stud

y (y

ear)

Pati

ents

(n)

Sam

ple

popu

lati

onD

urat

ion

Sett

ing

inte

rven

tion

des

crip

tion

Stud

y de

sign

Type

of c

ontr

olRe

f.

Gia

lam

as

et al.

(200

9)Re

crui

ted:

49

68D

ata

anal

yzed

: 43

81

Indi

vidu

als

with

T1D

M o

r T2

DM

with

hyp

erlip

idem

ia

or re

quiri

ng a

ntic

oagu

lant

th

erap

y

2 ye

ars

53 A

ustr

alia

n ge

nera

l pr

actic

es in

urb

an,

rura

l and

rem

ote

area

s

Bloo

d an

d ur

ine

sam

ples

test

ed u

sing

po

int-

of-c

are

devi

ces

with

in th

eir g

ener

al

prac

tices

RCT

Usu

al c

are:

bl

ood

test

ed

by u

sual

pa

thol

ogy

labo

rato

ry

[24]

Gla

sgow

et al.

(201

0)46

3H

eter

ogen

eous

sam

ple

of

adul

ts w

ith T

2DM

4 m

onth

s5

prim

ary

care

cl

inic

s w

ithin

Ka

iser

Per

man

ente

Co

lora

do (C

O, U

SA)

Inte

rnet

-bas

ed D

MSM

pro

gram

RCT

Enha

nced

usu

al

care

[25]

Gla

sgow

et al.

(201

2)46

3A

dults

age

d 25

–75

year

s w

ith a

BM

I of ≥

25 a

nd

biw

eekl

y ac

cess

to th

e in

tern

et

12 m

onth

sPr

imar

y cl

inic

s w

ithin

Ka

iser

Per

man

ente

Co

lora

do (C

O, U

SA)

Inte

rnet

-bas

ed, c

ompu

ter-

assi

sted

DM

SM

com

pare

d w

ith c

ompu

ter-

base

d pr

ogra

m w

ith

soci

al s

uppo

rt

Prag

mat

ic

RCT

Enha

nced

usu

al

care

: com

pute

r-ba

sed

risk

appr

aisa

l

[26]

Gra

nt et a

l. (2

003)

232

Indi

vidu

als w

ith T

2DM

who

ha

d un

derg

one

labo

rato

ry

test

ing

in th

e pr

eced

ing

year

and

had

vis

ited

the

clin

ic 6

mon

ths p

rece

ding

th

e st

udy

3 m

onth

sA

cade

mic

-affi

liate

d co

mm

unit

y he

alth

ce

nter

Phar

mac

ist a

dmin

iste

red

deta

iled

ques

tionn

aire

s, p

rovi

ded

tailo

red

educ

atio

n re

gard

ing

med

icat

ion

use

and

help

with

ap

poin

tmen

t ref

erra

l

Pros

pect

ive

RCT

Usu

al c

are

[27]

Jara

b et al.

(201

2)17

1A

dults

with

T2D

M

atte

ndin

g an

out

patie

nt

diab

etes

clin

ic

6 m

onth

sRo

yal M

edic

al

Serv

ices

Hos

pita

l (J

orda

n)

A c

linic

al p

harm

acis

t-le

d ph

arm

aceu

tical

car

e pr

ogra

m d

eliv

ered

ant

idia

betic

ther

apy

and

adju

nct t

hera

py to

pat

ient

s

RCT

Usu

al c

are

[28]

Kim

et a

l. (2

006)

45In

divi

dual

s ag

ed ≥

30 y

ears

w

ith in

tern

et a

t hom

e12

wee

ksU

rban

are

a in

Sou

th

Kore

aU

sed

onlin

e si

te to

ent

er a

nd m

onito

r blo

od

gluc

ose

leve

ls a

nd d

rug

info

rmat

ion,

with

su

ppor

t fro

m a

nur

se th

roug

h w

eekl

y SM

S m

essa

ges

Qua

si-

expe

rimen

tal,

1 gr

oup,

pr

e–po

st-t

est

N/A

[29]

Kras

s et al.

(200

5)18

8D

iagn

osed

with

T2D

M,

taki

ng >

3 m

edic

atio

ns,

aged

18–

85 y

ears

, abl

e to

co

mpl

ete

ques

tionn

aire

s

9 m

onth

sRe

gion

s of

New

So

uth

Wal

es

(Aus

tral

ia)

Patie

nts

wer

e gi

ven

inst

ruct

ions

on

BGSM

us

ing

Med

iSen

se; d

iabe

tes

hist

ory,

info

rmat

ion

on q

ualit

y of

life

, med

icat

ion

adhe

renc

e,

clin

ical

dat

a an

d m

edic

atio

n hi

stor

y w

ere

used

to

dev

elop

pat

ient

pro

toco

ls; i

nter

vent

ion

stra

tegi

es in

clud

ed B

GSM

leve

ls, e

duca

tion

abou

t the

dis

ease

and

med

icat

ions

, adh

eren

ce

devi

ces,

rem

inde

rs, a

nd re

gula

r fol

low

-up

Para

llel

grou

p,

repe

ated

m

easu

re

desi

gn

Usu

al c

are

[30]

Neg

aran

deh

et al.

(201

3)13

5A

dults

dia

gnos

ed fo

r >6

mon

ths

with

low

lit

erac

y (T

OFH

LA ≤

59)

6 w

eeks

Dia

bete

s cl

inic

in

Kurd

ista

nTw

o ed

ucat

iona

l str

ateg

ies

(teac

h ba

ck a

nd

pict

oria

l im

age)

usi

ng th

e sa

me

educ

atio

nal

cont

ent

RCT

Usu

al d

iabe

tes

educ

atio

n[31]

BGSM

: Blo

od g

luco

se m

onito

ring;

CH

W: C

omm

unit

y he

alth

wor

ker;

CM

: Cas

e m

anag

er; D

MSM

: Dia

bet

es m

ellit

us s

elf-

man

agem

ent;

N/A

: Not

app

licab

le; R

CT:

Ran

dom

ized

con

trol

led

tria

l; T1

DM

: Typ

e 1

diab

etes

mel

litus

; T2

DM

: Typ

e 2

diab

etes

mel

litus

; TO

FHLA

: Tes

t of F

unct

iona

l Hea

lth L

itera

cy in

Adu

lts.



ble

1. S

tudi

es m

eeti

ng in

clus

ion

crite

ria

(con

t.).

Stud

y (y

ear)

Pati

ents

(n)

Sam

ple

popu

lati

onD

urat

ion

Sett

ing

inte

rven

tion

des

crip

tion

Stud

y de

sign

Type

of c

ontr

olRe

f.

Ode

gard

et al.

(200

5)77

Adu

lts w

ith T

2DM

ta

king

at l

east

one

ora

l T2

DM

med

icat

ion

and

HbA

1c ≥

9%

12 m

onth

sN

onpr

ofit m

edic

al

clin

ics i

n gr

eate

r Se

attle

are

a (W

A,

USA

)

Phar

mac

ist i

nter

vent

ion

with

a d

evel

oped

T2

DM

car

e pl

an a

nd p

harm

acis

t–pa

tient

/ph

arm

acis

t–pr

ovid

er c

omm

unic

atio

n on

pa

tient

pro

gres

s

RCT

Usu

al c

are

[32]

Ode

gard

et al.

(201

2)26

5Pa

tient

s with

T2D

M ta

king

or

al T

2DM

med

icat

ions

and

la

te fo

r refi

lls b

y ≥6

day

s

18 m

onth

sFo

ur c

omm

unit

y ch

ain

phar

mac

ies

in

Seat

tle (W

A, U

SA)

Tele

phon

e-in

itiat

ed a

dher

ence

sup

port

by

phar

mac

ists

follo

win

g m

isse

d re

fill a

lert

s fr

om

com

pute

r

RCT

Usu

al c

are

[33]

Ruba

k et al.

(201

1)80

Indi

vidu

als

aged

40

–69

year

s w

ith T

2DM

12 m

onth

sD

enm

ark

Effec

t of m

otiv

atio

nal i

nter

view

trai

ning

on

gene

ral p

ract

ition

ers

and

qual

ity

of c

are

mea

sure

s in

pat

ient

s w

ith T

2DM

RCT

Stan

dard

car

e [34]

Tan et al.

(201

1)16

4A

dults

with

poo

rly

cont

rolle

d T2

DM

12 w

eeks

Mal

aysi

aBr

ief s

truc

ture

d di

abet

es e

duca

tion

prog

ram

ba

sed

on s

elf-

effica

cySi

ngle

-bl

inde

d RC

TSt

anda

rd c

are

[35]

Thie

baud

et al.

(200

8)25

98A

dults

that

did

not

opt

out

of

car

e m

anag

emen

t2

year

sFl

orid

a M

edic

aid

bene

ficia

ries

(FL,

USA

)

Tele

phon

e ed

ucat

ion

of M

edic

aid

bene

ficia

ries

on c

hron

ic d

isea

ses

and

incr

easi

ng

self-

man

agem

ent a

bilit

ies

Coho

rtM

atch

ed

mod

erat

e-to

-hig

h ris

k be

nefic

iarie

s w

ith d

iabe

tes

[36]

Thoo

len

et al.

(200

8)22

7In

divi

dual

s ag

ed

50–7

0 ye

ars

and

rece

ivin

g tr

eatm

ent

12 w

eeks

The

Net

herla

nds

Gro

up m

eetin

gs to

teac

h ne

cess

ary

skill

s to

an

ticip

ate

and

deal

with

pot

entia

l bar

riers

to

goal

mai

nten

ance

thro

ugh

proa

ctiv

e co

ping

RCT

Broc

hure

on

diab

etes

sel

f-m

anag

emen

t

[37]

Verv

loet

et al.

(201

1)10

4A

dults

usi

ng m

edic

atio

n fo

r at l

east

1 y

ear w

ith lo

w

adhe

renc

e

6 m

onth

sD

utch

pha

rmac

ies

(The

Net

herla

nds)

Two

inte

rven

tion

grou

ps w

ith e

lect

roni

c di

spen

sers

; one

gro

up re

ceiv

ed a

SM

S re

min

der

if th

ey h

ad n

ot o

pene

d th

eir d

ispe

nser

RCT

No

use

of S

MS

with

ele

ctro

nic

mon

itorin

g

[38]

Wak

efiel

d et al.

(201

2)30

2A

dults

with

T2D

M a

nd

hype

rten

sion

trea

ted

by

a Ve

tera

ns A

ffairs

prim

ary

care

pro

vide

r

12 m

onth

sIo

wa

City

Vet

eran

s A

ffairs

Med

ical

Ce

nter

(IA

, USA

)

Patie

nts

in th

e in

terv

entio

n gr

oup

ente

red

bloo

d pr

essu

re a

nd b

lood

glu

cose

mea

sure

s in

to a

hom

e te

lehe

alth

dev

ice

and

rece

ived

ed

ucat

iona

l fee

dbac

k

RCT

Usu

al c

are

[39]

Wol

ever

et al.

(201

0)56

Div

erse

sam

ple

of a

dults

w

ith T

2DM

6 m

onth

sCo

mm

unit

y se

rvic

ed

by D

uke

Uni

vers

ity

Scho

ol o

f Med

icin

e (N

C, U

SA)

14 3

0-m

in in

tegr

ativ

e co

achi

ng s

essi

ons

by

tele

phon

e Pr

e–po

st-t

est

Usu

al c

are

[40]

Zolfa

ghar

i et al.

(201

2)77

Recr

uite

d fr

om th

e Ira

nian

D

iabe

tes

Ass

ocia

tion,

ag

ed 1

8–65

yea

rs, m

ust

have

tele

phon

e ac

cess

in

thei

r hom

es a

nd h

ave

a m

obile

pho

ne, m

ust b

e on

ly u

sing

ora

l med

icat

ion

6 m

onth

sTe

hran

Uni

vers

ity

of M

edic

al S

cien

ce

(Iran

)

The

SMS

grou

p re

ceiv

ed 6

mes

sage

s/w

eek

rega

rdin

g ex

erci

se, t

akin

g T2

DM

med

icat

ion,

di

et, B

GSM

and

str

ess m

anag

emen

t. Th

e te

leph

one

grou

p in

volv

ed sc

hedu

ling

appo

intm

ents

, cou

nsel

ing

abou

t the

nat

ure

of th

e di

seas

e, ri

sk fa

ctor

s, im

port

ance

of

mai

ntai

ning

nor

mal

blo

od g

luco

se le

vels

, die

t, ex

erci

se, m

edic

atio

n ta

king

, illn

ess m

anag

emen

t an

d ho

w to

reco

rd b

lood

glu

cose

leve

ls

Qua

si-

expe

rimen

tal,

2 gr

oups

, pr

e–po

st-t

est

Para

llel

inte

rven

tion,

no

con

trol

gr

oup

[41]

BGSM

: Blo

od g

luco

se m

onito

ring;

CH

W: C

omm

unit

y he

alth

wor

ker;

CM

: Cas

e m

anag

er; D

MSM

: Dia

bet

es m

ellit

us s

elf-

man

agem

ent;

N/A

: Not

app

licab

le; R

CT:

Ran

dom

ized

con

trol

led

tria

l; T1

DM

: Typ

e 1

diab

etes

mel

litus

; T2

DM

: Typ

e 2

diab

etes

mel

litus

; TO

FHLA

: Tes

t of F

unct

iona

l Hea

lth L

itera

cy in

Adu

lts.



evidence available in the literature. The risk of bias across studies is discussed in this article and the discussion gives more weight to studies using a RCT design.

Results Study selection

Figure 1 shows the results of the search. After duplicates were removed, the search resulted in 922 citations for review. Title review produced 171 abstracts to examine, after which 56 articles were determined eligible for full article review. Twenty-seven eligible studies were identified based on the predetermined eligibility criteria [15–41]. Seventeen studies showed a statistically significant change in medication adherence for interventions with or without comparison groups, and ten studies reported significant statistical changes in glycemic control. Seven of the studies described interventions that sig-nificantly improved both medication adherence and HbA1c.

Study characteristics & results of individual studiesTable 1 provides a summary of the 27 studies that were eligible for inclusion; these studies are heterogeneous in terms of sample size, sample population, length of duration, setting, inter-vention description, study design and use of a control group. Sample sizes ranged from 23 to 29,247, and intervention duration stretched from 2 weeks to 2 years. Eighteen of the stud-ies were RCTs [15,18–19,22–28,31–35,37–39], four were pre–post-test [16–17,21,40], two combined quasiexperimental with pre- and post-tests [29,41], two were cohorts [20,36], and one used a parallel group with repeated measure design [30]. Twenty-three of the studies used a control group for comparisons [15,17–20,22–28,30–40]. All of the studies focused on adults with T2DM [15–41], but one study also included individuals diagnosed with Type 1 diabetes [24]. Thirteen of the 27 articles were conducted in international locations [15,22–24,28–31,34–35,37–38,41].

Table 2 presents the medication adherence outcomes of studies meeting the inclusion crite-ria [15–41]. The mean baseline medication adher-ence was wide ranging and fluctuated through-out the studies, particularly given the variety of adherence methods – direct and indirect – used. Direct measures of adherence indicate that med-ications have actually been taken by the patients and indirect measures, those most commonly

used, infer an assumption that medications have been taken by patients [11]. No direct methods for measuring medication adherence were used. All forms of indirect methods were used, with 18 studies measuring medication adherence by self-report [15–17,21,23–32,35,37,39–41], two by pill count [22,33], three by electronic devices [18–19,38], and three by pharmacy claims data [20,34,36]. Of the 27 studies, 13 reported statistically sig-nificant differences in medication adherence in the intervention group compared with the control group [15,17–20,22,24,28,30–31,33,36,40]. All four studies without a control group reported statistically significant changes in medication adherence [16,21,29,41].

Table 3 shows glycemic control outcomes of the studies that met the eligibility criteria [15–23,25–30,32,34–35,39–42] for which the impact on glycemic control was noted. The mean base-line HbA1c ranged from 6.8 to 10.6. One of the studies included in this review [39] reported outcomes for medication adherence and gly-cemic control in two separate papers; thus, a second article using the same population and intervention, reporting the differences in HbA1c between groups, is reported in Table 3 [42]. Eight out of 18 studies demonstrated sta-tistically significant improvements in HbA1c between the intervention groups and the control groups [15,17–19,22,28,34–35]. In these studies, the percentage change in HbA1c in the interven-tion group ranged from -1.57 to -0.15 compared with -2.1 to +0.2 in the control group; this also varied at different time points within the stud-ies. Of the four studies without a control group, two described statistically significant changes in HbA1c [21,29]. For one study, there was a -0.6% drop in the HbA1c, while the percentage change was -1.1% in the other.

Table 4 illustrates intervention characteris-tics of the 27 studies included in this review. Most studies did not employ a theoretical foundation [15–16,20–22,24–25,27–34,36,38–41], but for those that did, one study used the Theory of Planned Behavior [23], one used the Trans-theoretical Model [17], two used a self-efficacy theory [35,37], two used integrated care [18–19], and one used the Social–Cognitive Theory [26]. As for the intervention characteristics, five out of the 27 studies were culturally tai-lored [16,18,31,38–39], of which four were signifi-cant for changes in medication adherence and HbA1c. Self-management was the focus of several interventions, with 18 concentrating on



ble

2. M

edic

atio

n ad

here

nce

outc

omes

of s

tudi

es m

eeti

ng in

clus

ion

crite

ria.

Stud

y (y

ear)

Mea

sure

of

med

icat

ion

adhe

renc

e

Mea

n ±

SD b

asel

ine

med

icat

ion

adhe

renc

ein

terv

enti

on m

ean

± SD

ch

ange

in m

edic

atio

n ad

here

nce

Cont

rol m

ean

± SD

ch

ange

in m

edic

atio

n ad

here

nce

Stat

isti

cal s

igni

fican

ceRe

f.

Al M

azro

ui

et al.

(200

9)Se

lf-re

port

: fo

rget

ting,

mis

sing

or

incr

easi

ng d

oses

Inte

rven

tion:

48.

3% n

onad

here

ntCo

ntro

l: 49

.1%

non

adhe

rent

21.4

% o

f int

erve

ntio

n gr

oup

wer

e no

nadh

eren

t at

12-m

onth

follo

w-u

p

32.5

% o

f con

trol

gro

up

wer

e no

nadh

eren

t at

12-m

onth

follo

w-u

p

Gly

cem

ic c

ontr

ol a

nd h

ealth

-rel

ated

qu

alit

y of

life

wer

e si

gnifi

cant

ly

impr

oved

aft

er re

ceiv

ing

patie

nt

educ

atio

n an

d m

edic

atio

n ad

here

nce

advi

ce (p

= 0

.003

)

[15]

Aro

ra et a

l. (2

012)

Self-

repo

rt: M

MA

SSc

ore

of 3

.5 o

n M

MA

SSc

ore

of 4

.75

on M

MA

S at

3-

wee

k fo

llow

-up

No

cont

rol g

roup

The

pilo

t int

erve

ntio

n de

mon

stra

ted

incr

ease

d he

alth

y be

havi

ors

with

im

prov

ed d

iabe

tes

self-

effica

cy a

nd

med

icat

ion

adhe

renc

e

[16]

Baba

mot

o et al.

(200

9)Se

lf-re

port

(p

erce

ntag

e w

ho

neve

r for

get t

o ta

ke

med

icat

ion)

Inte

rven

tion:

CH

W: 6

9% n

ever

forg

ot to

take

m

edic

atio

nCM

: 77%

nev

er fo

rgot

to ta

ke

med

icat

ion

Cont

rol:

67%

nev

er fo

rgot

to ta

ke m

edic

atio

n

79%

nev

er fo

rgot

to ta

ke

med

icat

ion

in th

e CH

W

inte

rven

tion,

55%

nev

er

forg

ot to

take

med

icat

ion

in th

e CM

inte

rven

tion

50%

nev

er fo

rgot

to ta

ke

med

icat

ion

in th

e co

ntro

l gr

oup

Med

icat

ion-

taki

ng b

ehav

ior

rem

aine

d un

chan

ged

(p >

0.0

5) in

th

e CH

W g

roup

, but

wor

sene

d in

the

CM a

nd c

ontr

ol g

roup

s (p

< 0

.05)

[17]

Bogn

er et a

l. (2

010)

Elec

tron

ic

mon

itorin

g (M

EMS

>80%

adh

eren

t)

34.5

% in

terv

entio

n20

.7%

con

trol

62.1

%24

.1%

Prop

ortio

n of

par

ticip

ants

who

had

80

% a

dher

ence

to h

ypog

lyce

mic

ag

ent w

as g

reat

er in

the

inte

rven

tion

than

the

cont

rol g

roup

(p =

0.0

04)

[18]

Bogn

er et a

l. (2

012)

Elec

tron

ic

mon

itorin

g (M

EMS

>80%

adh

eren

t)

42.0

% in

terv

entio

n35

.9%

con

trol

At 6

wee

ks, t

he

inte

rven

tion

grou

p w

as

61%

adh

eren

t, an

d 65

%

adhe

rent

at 1

2 w

eeks

At 6

wee

ks, t

he c

ontr

ol

grou

p w

as 3

5% a

dher

ent,

and

30%

adh

eren

t at

12 w

eeks

At 6

and

12

wee

ks, t

hose

in th

e in

terv

entio

n gr

oup

had

sign

ifica

nt

impr

ovem

ent i

n ad

here

nce

com

pare

d w

ith u

sual

car

e (p

≤ 0

.001

)

[19]

Bren

nan

et al.

(201

2)To

tal n

umbe

r of

days

of m

edic

atio

n su

pplie

d pe

r mon

th

CVS

Ret

ail:

Inte

rven

tion:

No

rece

nt u

se o

f ACE

inhi

bito

rs:

31.2

%N

o re

cent

use

of s

tatin

s: 3

2.6%

Cont

rol:

No

rece

nt u

se o

f ACE

inhi

bito

rs:

31.6

%N

o re

cent

use

of s

tatin

s: 3

2.4%

Mai

l ord

er:

Inte

rven

tion:

No

rece

nt u

se o

f ACE

inhi

bito

rs:

32.1

%N

o re

cent

use

of s

tatin

s: 3

2.8%

Cont

rol:

No

rece

nt u

se o

f ACE

inhi

bito

rs:

31.3

%N

o re

cent

use

of s

tatin

s: 3

1.9%

3.9%

incr

ease

in s

uppl

y pe

r mon

th in

reta

il in

terv

entio

n gr

oup

com

pare

d w

ith c

ontr

ol

grou

p; 1

.7%

incr

ease

in

supp

ly p

er m

onth

in m

ail

orde

r int

erve

ntio

n gr

oup

com

pare

d w

ith c

ontr

ol

grou

p

N/A

Ther

e w

as a

sta

tistic

ally

sig

nific

ant

diffe

renc

e be

twee

n th

e tw

o in

terv

entio

ns (p

< 0

.01)

[20]

BMQ

: Brie

f med

icat

ion

ques

tionn

aire

; CH

W: C

omm

unit

y he

alth

wor

ker;

CM

: Cas

e m

anag

er; M

ARS

: Med

icat

ion

adhe

renc

e re

por

t sca

le; M

EMS:

Med

icat

ion

Even

t Mon

itorin

g Sy

stem

; MM

AS:

Mor

isky

Med

icat

ion

Adh

eren

ce S

cale

; M

PR: M

edic

atio

n p

osse

ssio

n ra

te; N

/A: N

ot a

pplic

able

; RTM

M: R

eal-t

ime

med

icat

ion

mon

itorin

g; S

D: S

tand

ard

devi

atio

n; S

DSC

A: S

umm

ary

of d

iab

etes

sel

f-ca

re a

ctiv

ities

; T2D

M: T

ype

2 di

abet

es m

ellit

us.



Tabl

e 2.

Med

icat

ion

adhe

renc

e ou

tcom

es o

f stu

dies

mee

ting

incl

usio

n cr

iteri

a (c

ont.)

.

Stud

y (y

ear)

Mea

sure

of

med

icat

ion

adhe

renc

e

Mea

n ±

SD b

asel

ine

med

icat

ion

adhe

renc

ein

terv

enti

on m

ean

± SD

ch

ange

in m

edic

atio

n ad

here

nce

Cont

rol m

ean

± SD

ch

ange

in m

edic

atio

n ad

here

nce

Stat

isti

cal s

igni

fican

ceRe

f.

Cast

illo et al.

(201

0)Se

lf-re

port

: SD

SCA

5.5

± 2.

5 (p

rete

st)

6.6

± 1.

3 (p

ost-

test

)N

/ASi

gnifi

cant

pre

–pos

t im

prov

emen

t in

adh

eren

ce (p

= 0

.009

)[21]

Chan

et a

l. (2

012)

Pill

coun

t (p

erce

ntag

e th

at

are

at le

ast 8

0%

com

plia

nt b

ased

on

num

ber t

aken

as

a p

erce

ntag

e of

co

rrec

t am

ount

)

73.6

% in

terv

entio

n82

.1%

con

trol

The

prop

ortio

n of

in

divi

dual

s w

ho w

ere

at le

ast 8

0% a

dher

ent

incr

ease

d by

22.

5 ±

13.4

%

The

prop

ortio

n of

in

divi

dual

s w

ho w

ere

at le

ast 8

0% a

dher

ent

incr

ease

d 2

± 5.

0%

Inte

rven

tion

grou

p ha

d gr

eate

r im

prov

emen

t in

com

plia

nce

com

pare

d w

ith c

ontr

ol (p

< 0

.001

)

[22]

Farm

er et a

l. (2

012)

Self-

repo

rt: M

ARS

(s

cale

: 5–2

5)In

terv

entio

n: 2

3.6

± 2.

3 sc

ore

on M

ARS

Cont

rol:

23.6

± 2

.8 s

core

on

MA

RS23

.6 ±

2.6

sco

re o

n M

ARS

; -0

.4 (9

5% C

I: -1

.0 to

0.2

)24

.1 ±

1.6

sco

re o

n M

ARS

Ther

e w

as n

o st

atis

tical

ly s

igni

fican

t di

ffere

nce

betw

een

the

cont

rol a

nd

inte

rven

tion

grou

ps (p

= 0

.2)

[23]

Gia

lam

as

et al.

(200

9)Se

lf-re

port

via

the

MA

RS-5

Med

ian

scor

e of

24

(max

imum

sco

re: 2

5)N

/AN

/AIn

terv

entio

n gr

oup

had

high

er

adhe

renc

e th

an c

ontr

ols

with

a

noni

nfer

iorit

y m

argi

n of

-4.1

% (3

9.3

vs 3

7.0%

; p <

0.0

01)

[24]

Gla

sgow

et al.

(201

0)Se

lf-re

port

: Hill

–Bo

ne C

ompl

ianc

e Sc

ale

(sca

le: 0

–1)

Inte

rven

tion

scor

e: 3

.80

± 0.

29Co

ntro

l sco

re: 3

.77

± 0.

303.

84 ±

0.2

93.

79 ±

0.3

9N

o si

gnifi

cant

impr

ovem

ents

in

adhe

renc

e (p

= 0

.262

)[25]

Gla

sgow

et al.

(201

2)Se

lf-re

port

: Hill

–Bo

ne C

ompl

ianc

e Sc

ale

(sca

le: 0

–1)

Inte

rven

tion

scor

e: 0

.35

± 0.

03Co

ntro

l sco

re: 0

.34

± 0.

04

Post

inte

rven

tion

scor

es:

4 m

onth

s: 0

.42

± 0.

03

12 m

onth

s: 0

.43

± 0.

03

Post

stud

y sc

ores

:4

mon

ths:

0.3

8 ±

0.04

12

mon

ths:

0.4

1 ±

0.04

No

stat

istic

al s

igni

fican

ce b

etw

een

inte

rven

tions

and

con

trol

gro

ups

[26]

Gra

nt et a

l. (2

003)

Self-

repo

rt: n

umbe

r of

day

s w

ithou

t m

issi

ng m

edic

atio

n

Inte

rven

tion:

6.7

± 0

.9 d

ays

with

out

mis

sing

med

icat

ion

in th

e pa

st 7

day

s Co

ntro

l: 6.

9 ±

0.4

days

with

out m

issi

ng

med

icat

ion

in th

e pa

st 7

day

s

0.1

± 1

days

with

out

mis

sing

med

icat

ion

in th

e pa

st 7

day

s at

3-m

onth

fo

llow

-up

0.1

± 0.

4 da

ys w

ithou

t m

issi

ng m

edic

atio

n in

the

past

7 d

ays

at 3

-mon

th

follo

w-u

p

Ther

e w

as n

ot a

sta

tistic

ally

si

gnifi

cant

diff

eren

ce w

hen

com

parin

g th

e in

terv

entio

n an

d co

ntro

l gro

ups

(p =

0.8

)

[27]

Jara

b et al.

(201

2)Se

lf-re

port

: MM

AS

Inte

rven

tion:

74.

1% n

onad

here

ntCo

ntro

l: 70

.9%

non

adhe

rent

28.6

% o

f the

inte

rven

tion

grou

p w

ere

nona

dher

ent

post

inte

rven

tion

at

6-m

onth

follo

w-u

p

64.6

% o

f the

con

trol

gr

oup

wer

e no

nadh

eren

t po

stin

terv

entio

n at

6-

mon

th fo

llow

-up

At t

he 6

-mon

th fo

llow

-up

inte

rven

tion

patie

nts

wer

e m

ore

adhe

rent

to m

edic

atio

ns th

an th

e co

ntro

l gro

up (p

= 0

.003

)

[28]

Kim

et a

l. (2

006)

Self-

repo

rt: n

umbe

r of

day

s in

wee

k w

hen

med

icat

ion

was

take

n

4.8

± 2.

6 da

ys+1

.1 d

ays

N/A

Ther

e w

as a

sta

tistic

ally

sig

nific

ant

chan

ge in

the

num

ber o

f day

s of

m

edic

atio

n ad

here

nce

in a

wee

k in

th

e in

terv

entio

n gr

oup

(p =

0.0

32)

[29]

BMQ

: Brie

f med

icat

ion

ques

tionn

aire

; CH

W: C

omm

unit

y he

alth

wor

ker;

CM

: Cas

e m

anag

er; M

ARS

: Med

icat

ion

adhe

renc

e re

por

t sca

le; M

EMS:

Med

icat

ion

Even

t Mon

itorin

g Sy

stem

; MM

AS:

Mor

isky

Med

icat

ion

Adh

eren

ce S

cale

; M

PR: M

edic

atio

n p

osse

ssio

n ra

te; N

/A: N

ot a

pplic

able

; RTM

M: R

eal-t

ime

med

icat

ion

mon

itorin

g; S

D: S

tand

ard

devi

atio

n; S

DSC

A: S

umm

ary

of d

iab

etes

sel

f-ca

re a

ctiv

ities

; T2D

M: T

ype

2 di

abet

es m

ellit

us.



ble

2. M

edic

atio

n ad

here

nce

outc

omes

of s

tudi

es m

eeti

ng in

clus

ion

crite

ria

(con

t.).

Stud

y (y

ear)

Mea

sure

of

med

icat

ion

adhe

renc

e

Mea

n ±

SD b

asel

ine

med

icat

ion

adhe

renc

ein

terv

enti

on m

ean

± SD

ch

ange

in m

edic

atio

n ad

here

nce

Cont

rol m

ean

± SD

ch

ange

in m

edic

atio

n ad

here

nce

Stat

isti

cal s

igni

fican

ceRe

f.

Kras

s et al.

(200

5)Se

lf-re

port

: BM

Q

(sca

le: 0

–7)

Inte

rven

tion:

1.3

8 ±

1.20

BM

Q s

core

Cont

rol:

1.01

± 0

.88

BMQ

sco

reBM

Q s

core

of 0

.94

± 0.

89BM

Q s

core

of 1

.16

± 0.

88

The

BMQ

sco

res

wer

e st

atis

tical

ly

sign

ifica

nt w

hen

com

parin

g th

e in

terv

entio

n an

d co

ntro

l gro

ups

(p =

0.0

09)

[30]

Neg

aran

deh

et al.

(201

3)Se

lf-re

port

: MM

AS

(sca

le: 1

–7)

Inte

rven

tion:

Pict

ure

inte

rven

tion:

4.3

3 ±

1.62

Teac

h ba

ck in

terv

entio

n: 4

.37

± 1.

46Co

ntro

l: 4.

52 ±

1.7

4

Pict

ure

inte

rven

tion:

6.

73 ±

1.5

2 Te

ach

back

inte

rven

tion:

7.

03 ±

0.9

9

Cont

rol:

4.32

± 1

.58

Sign

ifica

nt d

iffer

ence

bet

wee

n tw

o in

terv

entio

n gr

oups

and

the

cont

rol

grou

p (p

< 0

.001

), bu

t no

diffe

renc

e be

twee

n in

terv

entio

n gr

oups

(p

= 0

.56)

[31]

Ode

gard

et al.

(200

5)Se

lf-re

port

: tw

o-qu

estio

n re

call

valid

ated

in a

ch

roni

c di

seas

e m

odel

Inte

rven

tion:

56%

had

diffi

cult

y re

mem

berin

g to

take

med

icat

ions

as

pres

crib

edCo

ntro

l: 35

% h

ad d

ifficu

lty

rem

embe

ring

to ta

ke m

edic

atio

ns a

s pr

escr

ibed

(p =

0.0

7)

Not

repo

rted

N

/ATh

e in

terv

entio

n ha

d no

effe

ct

on a

dher

ence

(p =

0.4

9) a

nd th

e co

ntro

l gro

up h

ad b

ette

r adh

eren

ce

thro

ugho

ut th

e st

udy

(p =

0.0

3)

[32]

Ode

gard

et al.

(201

2)Re

fill r

ate

base

d on

MPR

at 6

and

12

mon

ths

Inte

rven

tion:

74%

had

MPR

abo

ve 8

0%

for p

revi

ous

12 m

onth

sCo

ntro

l: 65

% h

ad M

PR a

bove

80%

for

prev

ious

12

mon

ths

MPR

sco

res

at 6

and

12

mon

ths

impr

oved

si

gnifi

cant

ly w

ithin

the

grou

p (p

= 0

.16

and

p<0.

01,

resp

ectiv

ely)

MPR

rem

aine

d un

chan

ged

at 6

and

12

mon

ths

Inte

rven

tion

grou

p si

gnifi

cant

ly

mor

e lik

ely

to h

ave

an M

PR >

80%

at

12

mon

ths

(odd

s ra

tio: 4

.77;

95

% C

I: 2.

00–1

1.4)

[33]

Ruba

k et al.

(201

1)N

umbe

r of

pres

crip

tions

‘c

ashe

d in

’ by

pat

ient

s at

pha

rmac

y co

mpa

red

with

nu

mbe

r of

pres

crip

tions

pr

escr

ibed

N/A

Ora

l ant

idia

betic

m

edic

atio

n: 3

7% c

ashe

d in

com

pare

d w

ith 3

9%

pres

crib

ed

Ora

l ant

idia

betic

m

edic

atio

n: 3

6% c

ashe

d in

com

pare

d w

ith 3

6%

pres

crib

ed

Ther

e w

ere

no s

tatis

tical

ly

sign

ifica

nt d

iffer

ence

s in

the

num

ber

of p

resc

riptio

ns c

ashe

d in

com

pare

d w

ith th

e nu

mbe

r of p

resc

riptio

ns

pres

crib

ed. N

o eff

ect o

f mot

ivat

iona

l in

terv

iew

ing

on m

edic

atio

n ad

here

nce

was

foun

d

[34]

Tan et al.

(201

1)Se

lf-re

port

(p

erce

ntag

e th

at

are

90%

adh

eren

t ba

sed

on n

umbe

r of

tim

es in

a w

eek

med

icat

ions

are

m

isse

d)

Inte

rven

tion:

84.

48%

Co

ntro

l: 85

%89

.21%

repo

rted

90%

ad

here

nce

base

d on

nu

mbe

r of t

imes

in a

wee

k m

edic

atio

ns a

re m

isse

d(9

1.42

% w

ere

adhe

rent

w

hen

adju

sted

for

chan

ged

adhe

renc

e du

e to

hy

perg

lyce

mia

)

84.4

8% w

ere

90%

ad

here

nt b

ased

on

num

ber o

f tim

es in

a w

eek

med

icat

ions

are

mis

sed

No

diffe

renc

e in

adh

eren

ce b

etw

een

grou

ps u

nles

s ad

just

men

ts in

in

sulin

wer

e co

nsid

ered

adh

eren

t, in

whi

ch c

ase

ther

e w

as a

sig

nific

ant

diffe

renc

e (p

= 0

.008

)

[35]

BMQ

: Brie

f med

icat

ion

ques

tionn

aire

; CH

W: C

omm

unit

y he

alth

wor

ker;

CM

: Cas

e m

anag

er; M

ARS

: Med

icat

ion

adhe

renc

e re

por

t sca

le; M

EMS:

Med

icat

ion

Even

t Mon

itorin

g Sy

stem

; MM

AS:

Mor

isky

Med

icat

ion

Adh

eren

ce S

cale

; M

PR: M

edic

atio

n p

osse

ssio

n ra

te; N

/A: N

ot a

pplic

able

; RTM

M: R

eal-t

ime

med

icat

ion

mon

itorin

g; S

D: S

tand

ard

devi

atio

n; S

DSC

A: S

umm

ary

of d

iab

etes

sel

f-ca

re a

ctiv

ities

; T2D

M: T

ype

2 di

abet

es m

ellit

us.



Tabl

e 2.

Med

icat

ion

adhe

renc

e ou

tcom

es o

f stu

dies

mee

ting

incl

usio

n cr

iteri

a (c

ont.)

.

Stud

y (y

ear)

Mea

sure

of

med

icat

ion

adhe

renc

e

Mea

n ±

SD b

asel

ine

med

icat

ion

adhe

renc

ein

terv

enti

on m

ean

± SD

ch

ange

in m

edic

atio

n ad

here

nce

Cont

rol m

ean

± SD

ch

ange

in m

edic

atio

n ad

here

nce

Stat

isti

cal s

igni

fican

ceRe

f.

Thie

baud

et al.

(200

8)Ph

arm

acy

clai

ms

data

(pro

port

ion

user

s w

ith M

PR

≥80%

)

Inte

rven

tion:

30.

3% h

ad a

n M

PR ≥

80%

Cont

rol:

33%

had

an

MPR

≥80

%Ca

re m

anag

ed v

s no

t car

e m

anag

ed

+8.

7% n

onus

ers

at b

asel

ine

+6.

9% u

sers

at b

asel

ine

N/A

Care

-man

aged

pat

ient

s w

ere

mor

e lik

ely

to h

ave

a hi

gher

MPR

(p

< 0

.001

)

[36]

Thoo

len

et al.

(200

8)Se

lf-re

port

: MA

RS

(sca

le: 1

–5)

Inte

rven

tion:

4.8

MA

RS s

core

Cont

rol:

4.9

MA

RS s

core

MA

RS s

core

of 4

.9 a

t 3 a

nd

12 m

onth

sM

ARS

sco

re o

f 5.0

at 3

and

12

mon

ths

Ther

e w

as n

o st

atis

tical

ly s

igni

fican

t di

ffere

nce

betw

een

the

inte

rven

tion

and

cont

rol g

roup

s

[37]

Verv

loet

et al.

(201

1)El

ectr

onic

m

onito

ring

(RTM

M

mea

surin

g th

e nu

mbe

r of d

ays

with

out d

osin

g,

prop

ortio

n of

m

isse

d do

ses

and

prop

ortio

n of

dos

es

in s

tand

ardi

zed

time)

Not

repo

rted

Day

s w

ithou

t dos

ing:

11

.9 ±

18.

8M

isse

d do

ses:

14.

5 ±

15.7

Dos

es ta

ken

in a

gree

d tim

e:

56.7

± 2

3.8

Day

s w

ithou

t dos

ing:

13

.8 ±

14.

5M

isse

d do

ses:

19.

2 ±

16.0

Dos

es ta

ken

in a

gree

d tim

e: 3

8.7

± 23

.0

Patie

nts

who

rece

ived

rem

inde

rs

took

dos

es w

ithin

agr

eed

upon

w

indo

w (p

= 0

.003

), bu

t sho

wed

no

diff

eren

ce in

day

s w

ithou

t do

sing

(p =

0.2

83) o

r mis

sed

dose

s (p

= 0

.065

)

[38]

Wak

efiel

d et al.

(201

2)Se

lf-re

port

: T2

DM

Reg

imen

A

dher

ence

Sca

le

Low

- and

hig

h-in

tens

ity

inte

rven

tion:

99

.7%

adh

eren

ceCo

ntro

l: 99

.5%

adh

eren

ce

Low

-inte

nsit

y in

terv

entio

n:

99.8

% a

dher

ence

at

6-m

onth

follo

w-u

p an

d 99

.7%

at 1

2 m

onth

sH

igh-

inte

nsity

inte

rven

tion:

99

.6%

at 6

-mon

th

follo

w-u

p an

d 10

0% a

t 12

-mon

th p

ostin

terv

entio

n

99.6

% a

t 6-m

onth

fo

llow

-up;

98.

9%

at 1

2-m

onth

po

stin

terv

entio

n

Repo

rted

med

icat

ion

adhe

renc

e w

as h

igh

acro

ss g

roup

s at

all

thre

e tim

e po

ints

. No

sign

ifica

nt

chan

ges

wer

e fo

und.

At 1

2 m

onth

s po

stin

terv

entio

n p

= 0.

20

[39]

Wol

ever

et al.

(201

0)Se

lf-re

port

: MM

AS

Inte

rven

tion:

6.7

± 0

.96

MM

AS

scor

eCo

ntro

l: 6.

7 ±

1.25

MM

AS

scor

ePo

stin

terv

entio

n: 7

.2 ±

0.9

7 M

MA

S sc

ore

Post

stud

y: 6

.9 ±

1.2

5 M

MA

S sc

ore

Ther

e w

as a

sta

tistic

ally

sig

nific

ant

impr

ovem

ent i

n th

e in

terv

entio

n gr

oup

com

pare

d w

ith c

ontr

ol g

oup

(p =

0.0

04)

[40]

Zolfa

ghar

i et al.

(201

2)Se

lf-ca

re: T

2DM

qu

estio

nnai

reSM

S: 7

5.48

± 1

4.33

Tele

phon

e: 7

3.27

± 1

4.75

SMS:

15.

65 ±

2.7

2 ch

ange

in

adhe

renc

e sc

ore

Tele

phon

e: 2

1.46

± 7

.12

chan

ge in

adh

eren

ce s

core

N/A

Ther

e w

as a

sta

tistic

ally

sig

nific

ant

diffe

renc

e be

twee

n th

e in

terv

entio

n an

d co

ntro

l gro

ups

(p =

0.0

00)

[41]

BMQ

: Brie

f med

icat

ion

ques

tionn

aire

; CH

W: C

omm

unit

y he

alth

wor

ker;

CM

: Cas

e m

anag

er; M

ARS

: Med

icat

ion

adhe

renc

e re

por

t sca

le; M

EMS:

Med

icat

ion

Even

t Mon

itorin

g Sy

stem

; MM

AS:

Mor

isky

Med

icat

ion

Adh

eren

ce S

cale

; M

PR: M

edic

atio

n p

osse

ssio

n ra

te; N

/A: N

ot a

pplic

able

; RTM

M: R

eal-t

ime

med

icat

ion

mon

itorin

g; S

D: S

tand

ard

devi

atio

n; S

DSC

A: S

umm

ary

of d

iab

etes

sel

f-ca

re a

ctiv

ities

; T2D

M: T

ype

2 di

abet

es m

ellit

us.



ble

3. G

lyce

mic

con

trol

out

com

es o

f stu

dies

mee

ting

incl

usio

n cr

iteri

a.

Stud

y (y

ear)

Mea

n ±

SD b

asel

ine

HbA

1c (%

)in

terv

entio

n m

ean

± SD

ch

ange

in o

r mea

n ±

SD

post

inte

rven

tion

HbA

1c (%

)

Cont

rol m

ean

± SD

ch

ange

in m

edic

atio

n ad

here

nce

Stat

isti

cal s

igni

fican

ceRe

f.

Al M

azro

ui et a

l. (2

009)

Inte

rven

tion:

8.5

Cont

rol:

8.4

7.6

at 4

-mon

th fo

llow

-up

7.1 a

t 8-m

onth

follo

w-u

p6.

9 at

12-

mon

th fo

llow

-up

8.0

at 4

-mon

th fo

llow

-up

8.4

at 8

-mon

th fo

llow

-up

8.3

at 1

2-m

onth

follo

w-u

p

The

care

pro

gram

resu

lted

in b

ette

r gly

cem

ic c

ontr

ol fo

r in

terv

entio

n pa

tient

s co

mpa

red

with

con

trol

(p <

0.0

01)

[15]

Baba

mot

o et al.

(200

9)CH

W: 8

.6CM

: 8.5

Stan

dard

car

e co

ntro

l: 9.

5N

onco

ntac

t con

trol

: 7.5

CHW

: 7.2

CM: 7

.4St

anda

rd c

are

cont

rol:

7.4

Non

cont

act c

ontr

ol: 7

.7M

ean

HbA

1c d

ecre

ased

in C

HW

, CM

and

sta

ndar

d ca

re

cont

rol (

p

0.0

5)

[17]

Bogn

er et a

l. (2

010)

Inte

rven

tion:

7.3

Cont

rol:

7.3

6.7

± 2.

37.

9 ±

2.6

Part

icip

ants

who

rece

ived

inte

rven

tion

had

low

er H

bA1c

(p

= 0

.019

)[18]

Bogn

er et a

l. (2

012)

Inte

rven

tion:

7.2

Cont

rol:

7.0

-0.7

0 ±

1.32

0.50

± 1

.11Si

gnifi

cant

ly im

prov

ed m

ean

chan

ge in

HbA

1c c

ompa

red

with

usu

al c

are

(p <

0.0

01)

[19]

Cast

illo et al.

(201

0)8.

39 ±

1.9

67.

79 ±

1.6

7N

/ASi

gnifi

cant

pre

–pos

t-te

st re

duct

ion

in H

bA1c

(p <

0.0

01)

[21]

Chan

et a

l. (2

012)

Inte

rven

tion:

9.7

Cont

rol:

9.5

-1.5

7-0

.4H

bA1c

redu

ced

in in

terv

entio

n gr

oup

com

pare

d w

ith

cont

rol g

roup

(p <

0.0

01)

[22]

Farm

er et a

l. (2

012)

Inte

rven

tion:

8.3

7 ±

1.25

Cont

rol:

8.28

± 1

.22

8.34

± 1

.24

Cont

rol:

8.21

± 1

.32

Ther

e w

as n

o st

atis

tical

ly s

igni

fican

t diff

eren

ce b

etw

een

the

inte

rven

tion

and

cont

rol g

roup

(p =

0.6

4)[23]

Gla

sgow

et a

l. (2

010)

Inte

rven

tion:

8.1

3 ±

1.80

Cont

rol:

8.06

± 1

.76

7.95

± 1

.58

8.00

± 1

.58

No

sign

ifica

nt im

prov

emen

ts in

HbA

1c (p

= 0

.145

)[25]

Gla

sgow

et a

l. (2

012)

Inte

rven

tion:

8.1

4 ±

0.10

Cont

rol:

8.16

± 0

.16

8.00

± 0

.09

at 4

mon

ths

8.16

± 0

.09

at 1

2 m

onth

s8.

02 ±

0.1

4 at

4 m

onth

s8.

04 ±

0.1

4 at

12

mon

ths

No

sign

ifica

nt d

iffer

ence

bet

wee

n co

mbi

ned

inte

rven

tions

an

d co

ntro

l[26]

Gra

nt et a

l. (2

003)

Inte

rven

tion:

7.7

± 1

.7Co

ntro

l: 7.

5 ±

1.1

Not

repo

rted

Not

repo

rted

Not

repo

rted

[27]

Jara

b et al.

(201

2)8.

5-0

.8 a

t 6 m

onth

s po

stin

terv

entio

n+

0.1

at 6

mon

ths

post

inte

rven

tion

Patie

nts

in th

e in

terv

entio

n sh

owed

sig

nific

ant

impr

ovem

ent i

n H

bA1c

leve

ls c

ompa

red

with

the

cont

rol

grou

p (p

= 0

.019

)

[28]

Kim

et a

l. (2

006)

8.1

± 2.

1-1

.1 ±

2.1

No

cont

rol

Sign

ifica

nt c

hang

e in

mea

n H

bA1c

in in

terv

entio

n (p

= 0

.006

)[29]

Ode

gard

et a

l. (2

005)

Inte

rven

tion:

10.

2 ±

0.8

Cont

rol:

10.6

± 1

.4 (p

= 0

.11)

-1.5

at 6

mon

ths

-2 a

t 12

mon

ths

Mea

n H

bA1c

did

not

diff

er b

etw

een

grou

ps a

fter

12

mon

ths

(p =

0.6

1); h

owev

er, t

here

was

a s

igni

fican

t dec

reas

e in

H

bA1c

ove

r tim

e fo

r bot

h gr

oups

(p =

0.0

01)

[32]

Ruba

k et al.

(201

1)In

terv

entio

n: 6

.9Co

ntro

l: 6.

8-0

.7 a

t 12

mon

ths

post

inte

rven

tion

-0.7

at 1

2 m

onth

s po

stin

terv

entio

nSi

gnifi

cant

impr

ovem

ents

wer

e se

en in

bot

h gr

oups

po

stin

terv

entio

n (p

< 0

.01)

. No

stat

istic

ally

sig

nific

ant

diffe

renc

e re

port

ed b

etw

een

grou

ps

[34]

Tan et al.

(201

1)In

terv

entio

n: 9

.9Co

ntro

l: 9.

68.

759.

67Si

gnifi

cant

dec

reas

e in

HbA

1c re

lativ

e to

con

trol

(p <

0.0

01)

[35]

CH

W: C

omm

unit

y he

alth

wor

ker;

CM

: Cas

e m

anag

er; S

D: S

tand

ard

devi

atio

n.



education [16–18,20–23,25–26,28,31–32,34–36,39,41], nine focusing on skills training [15–18,20–21,35–37], and 13 helping with problem-solving [16–18,20–21,26–28,31,35–37,41]. Twelve of the studies emphasizing education – five focusing on skills and seven assisting with problem-solving – were significant for variations in medication adherence and/or HbA1c between groups and/or at differ-ent time points. Eight used monitoring data, such as providing results of self-monitored blood glucose readings to the provider [15,25,27,29,31,40–41] and, of these, four were significant for differ-ences in medication adherence and/or HbA1c. Fifteen studies provided one-on-one counsel-ing to patients [17–20,22,24,28–29,31–33,35–36,40–41] and 13 studies were significant for changes in medication adherence and/or HbA1c. The study designs for most of the interventions using one-on-one interactions were RCTs. A total of 14 studies utilized telehealth/telemedicine tech-nology: mobile phones [22,28,33,40], telephones [15,17,23,26,30,36,38–40] and the internet [18]. Of those using health technologies, three of the mobile usage studies and seven of the studies using telephones were significant for differ-ences in medication adherence and/or HbA1c. The study using internet delivery did not show significant differences. Facilitators were used for intervention delivery in some studies: eight used nurse educators [17,25,27,31,34,36–37,40], one used certified diabetes educators (CDEs) [35] and three used CHWs [16,31,34]. Six involved collaboration with the patients’ physicians [23,26,29–30,38–39]. Of the studies using facilita-tors that demonstrated statistical significance in medication adherence, five used nurses, three used CHWs and six used pharmacists. Five of the six studies collaborating with physi-cians were significant for medication adherence and/or HbA1c. Using CDEs showed statistical significance only for HbA1c, as did two of the studies using nurses and CHWs, and three using pharmacists and physician collaborations.

In this review, effective medication adher-ence was defined as a significance improvement at p < 0.05. It is worth mentioning that out of the 17 articles showing statistical significance in medication adherence, eight were RCTs, four used a pre–post design, two were cohort stud-ies, two were quasiexperimental with pre–post designs, and one used a parallel-group, repeated-measure design. The remaining studies were all RCTs, one of the strongest research designs, and did not show a statistically significant difference T

able

3. G

lyce

mic

con

trol

out

com

es o

f stu

dies

mee

ting

incl

usio

n cr

iteri

a (c

ont.)

.

Stud

y (y

ear)

Mea

n ±

SD b

asel

ine

HbA

1c

(%)

inte

rven

tion

mea

n ±

SD

chan

ge in

or m

ean

± SD

po

stin

terv

entio

n H

bA1c

(%)

Cont

rol m

ean

± SD

ch

ange

in m

edic

atio

n ad

here

nce

Stat

isti

cal s

igni

fican

ceRe

f.

Wak

efiel

d et al.

(201

2)Lo

w-in

tens

ity

inte

rven

tion:

7.2

Hig

h-in

tens

ity

inte

rven

tion:

7.1

Cont

rol:

7.2

Low

inte

nsit

y: -0

.4 a

t 6

mon

ths,

-0.4

4 at

12

Documents

Effective interventions to improve medication adherence in ... · disease characteristics, intra- and inter-personal factors, and environmental characteristics [1]. Patients, providers