effect of pharmacist's interventions on glycemic control in diabetic patients

Effect of Pharmacist’s Interventions on Glycemic Control in Diabetic Patients: A Systematic Review and Meta-analysis of Randomized Controlled TrialsNalinee Poolsup,1 Naeti Suksomboon,2* Methinee Intarates2 1 Department of Pharmacy, Faculty of Pharmacy, Silpakorn University, Nakhon-Pathom, 73000, Thailand 2 Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok, 10400, Thailand

Abstract Several clinical trials have evaluated the effect of pharmacists’ interventions. However, the results have been inconsistent. We performed a systematic review to evaluate the effect of pharmacists’ interventions on glycemic control in diabetes. Clinical trials of pharmacists’ interventions aimed at improving glycemic control in diabetes patients were identified through a systematic search of MEDLINE, CINAHL, Web of Science, the Cochrane Library, and THAILIS. The bibliographic databases were searched from their inceptions to the end of February 2012. The references lists of relevant articles were checked and experts were consulted. Studies were included if they were: i) randomized controlled trials of pharmacists’ interventions aimed at improving glycemic control in diabetes patients, ii) reporting HbA1c

as an outcome measure, iii) published in English or Thai, and iv) clearly describing details of pharmacists’ intervention. Treatment effect was estimated with the mean difference in the change of HbA1c levels from baseline between the intervention and the control groups. Twenty-two trials involving 2,808 patients were included. Pharmacists’ interventions included an assessment and adjustment of anti-diabetic medications, identification of drug-related problems, co-operation with physicians and other members of the health care team, offering diabetes booklets and special medication containers, providing education concerning self-management of diabetes, and reinforcement of diabetes management with pharmacotherapy and non-pharmacotherapy. This meta-analysis showed that pharmacists’ interventions can improve glycemic control in diabetes patients (mean difference -0.68%, 95% CI -0.87% to -0.49%, p < 0.00001). Thus, pharmacists can play an important role in diabetes management.

Keyword: systematic review, pharmaceutical care, glycemic control, diabetes

INTRODUCTION Uncontrolled diabetes leads to micro-vascular complications, namely, retinopathy, nephropathy, and neuropathy, and macrovascular complications, namely, congestive heart failure (CHF), cerebrovascular disease (CVD), and peripheral arterial disease (PAD).1 Pharmacist has recently been involved in multidisciplinary team. The role of pharmacist in diabetes care, including discharged counseling and providing patient education regarding disease

and medication, especially, drug related problem (DRP) monitoring,2-4 is the most important responsibility of pharmacist to their patients for positive outcomes such as improving quality of life and keeping targeted goal of hemoglobin A1c (HbA1c). Evidence is clear that improving glycemic control and preventing complications result in significant cost saving and improved quality of life.5 There have been a large number of clinical trials evaluating pharmacists’

*Corresponding author: Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand. E-mail: [email protected]

Original Article Mahidol University Journal of Pharmaceutical Sciences 2013; 40 (4), 17-30

N. Poolsup et al.18

interventions in diabetes mellitus (DM). However, the outcomes of these studies remain controversial. We conducted a systematic review and meta-analysis to assess the effect of pharmacists’ interventions on HbA1c level in diabetes patients.

METHODS Data sources

Reports of randomized controlled trials of pharmacists’ interventions aimed for good glycemic control in diabetes patients were identified through a systematic literature search of MEDLINE, CINAHL, the Cochrane Library, Web of Science, and the THAIland Library Integrated System (THAILIS). Literature searches were conducted from inception to the end of February 2012. The MeSH terms “pharmaceutical services”, “pharmacists”, and “diabetes mellitus” were used together with keywords “pharmaceutical care” and “pharmacy counseling”. Hand search was also performed on relevant journals in Thailand such as Journal of the Medical Association of Thailand, Thai Journal of Hospital Pharmacy. References of retrieved studies and reviews of the topic were hand searched and experts in the field were contacted for additional papers not captured by the search strategy.

Study selection

The studies were included in the review if they: 1) were randomized controlled trials of any pharmacists’ interventions compared with usual care in diabetes patients, including type 1, type 2, Gestational diabetes mellitus (GDM), or unspecified DM; 2) reported HbA1c as an outcome measure; 3) were published in English or Thai language; and 4) clearly described pharmacists’ intervention. Abstract presenta-tion was excluded.

Data extraction and quality assessment

Data extraction and study quality assessment were performed independently by two investigators using a standardized form. Disagreements were resolved by a third investigator. Data from individual studies were abstracted. Data recorded were

the year of publication, setting, country, duration of study, intervention frequency, number of visit, inclusion criteria and exclusion criteria of each trial, type of DM, concomitant drug and disease, sample size, age, duration of DM, details of pharmacists’ interventions and control intervention, and primary outcomes. Quality of randomized controlled trials included in this review was assessed using Maastricht-Amsterdam scale.6 The scale comprises 11 items to evaluate internal validity of the study results. Studies that met at least 6 of 11 quality criteria were of high quality. Those scoring less than 6 of the criteria were of low quality.

Statistical analysis

Treatment effect was estimated with a mean difference in the change of HbA1c level from baseline to final assessment between the intervention group and the control group. If the variances of change values were not provided, but the exact p-value of the mean difference between the intervention and the control groups was available, the p-value was used to impute the variance.7 If the variances of change values and the exact p-values of the mean difference were not provided, the pooled interstudy variances were imputed from studies reporting variances. The inverse variance-weighted method was used for the pooling of mean difference and the estimation of 95% confidence interval (CI).8 A random effects model was used when the Q-statistic for heterogeneity was significant at the level of 0.1,9 otherwise the fixed effects model was used.8 The degree of heterogeneity was quantified using the I2 statistic which is the percentage of total variation across studies due to heterogeneity.10 A funnel plot and Egger’s method11 were performed to assess publication bias. Statistical analysis was undertaken with RevMan version 5.1 (Cochrane Collaboration, Oxford, UK). The significant level was set at p < 0.05.

RESULTS Study characteristics

The initial search of the computerized

19Effect of Pharmacist’s Interventions on Glycemic Control in Diabetic Patients: A Systematic Review and Meta-analysis of Randomized Controlled Trials

database and hand search identified a total of 1,160 articles (Figure 1). After the initial screening, 44 trials were attained in the selection process. Among the 44 trials, 16 trials were excluded because they did not report glycemic control/HbA1c. Five trials were further excluded because they did not state clearly the role of pharmacist in the intervention group. One trial reported results in terms of median and interquartile range

and was then excluded. Only 22 randomized controlled trials met inclusion criteria and were included in the systematic review and meta-analysis. Characteristics of these trials are presented in Table 1. In general, there were no significant differences between patients in the intervention group and those in the control group with respect to age and duration of diabetes.

Figure 1. Flow diagram of study selection for meta-analysis

Those trials, involved patients with type 1, type 2, GDM, or unspecified DM and were reported between 1996 and 2012. The setting of trials included primary care unit, home care, community pharmacy, primary care hospital, tertiary care hospital, a university-affiliated internal medicine outpatient clinic, endocrine clinic, military hospital, and veteran medical center in the USA, Canada, Australia, Sweden, Spain, UAE, and Thailand. The duration of trials varied from 3 months to 2 years. Pharmacists’ intervention was given at different frequency, for example, once a week and once every 6 months. Number of visit ranged between 1 and 24 times. Pharmacists involved included registered pharmacist,12,20,26,32 clinical pharmacist,14,16-18,21,23,25,27,29,30 community pharmacist,22,24,28,32 clinical pharmacist with multidisciplinary team,19,31 certified diabetes educator pharmacists,13 specially trained pharmacists.15 The methods of follow-up were

face-to-face encounter and/or by telephone. Details of pharmacist’ interventions differed from trial to trial (Table 2 and 3) and encompassed the followings: diabetes education and counseling about drug, disease, diet, exercise, life style modification, and self-management, assessment and adjustment of antidiabetic medications, identifying and solving drug-related problems, co-operating with physician and other diabetes health care team, providing materials, leaflet, diabetes booklet and special medication containers, and monthly newsletter that enforced patients to achieve a target goal, reminding about annual eye and foot examinations, and providing additional information about smoking cessation, stop drinking alcohol. For the usual care group, patients continued to receive standard medical care provided by their physicians, other health care team, and with/without pharmacists depending on each study design (Table 2).

N. Poolsup et al.20

No.

St

udy

Setti

ng

Cou

ntry

D

urat

ion

In

terv

entio

n In

clus

ion

of

stud

y fr

eque

ncy

crite

ria

1

Jabe

r LA

199

612

A U

nive

rsity

-affi

liate

d in

tern

al

US

4 m

o 2-

4 w

eeks

/tim

e T2

DM

m

edic

ine

outp

atie

nt cl

inic

2 G

uirg

uis L

M 2

00113

C

hain

pha

rmac

y, sh

oppe

rs

Can

ada;

6

mo

< 1

mon

th/ti

me

T2D

M fo

r Alb

erta

a m

inim

um

drug

mar

t Ed

mon

ton,

of

1 y

ear,

non-

inst

itutio

naliz

ed

3 C

liffor

d RM

200

214

Frem

entle

Hos

pita

l,

Aust

ralia

6

mo

6 w

eeks

/tim

e A

ged

> 18

yea

rs w

ith e

ither

T1D

M

diab

etes

out

patie

nt cl

inic

or T

2DM

and

was

hig

h-ris

k

for t

he d

evel

opm

ent o

f dia

bete

s

com

plic

atio

ns.

4

Sark

adi A

200

415

Stoc

khol

m D

iabe

tes A

ssoc

iatio

n Sw

eden

24

mo

6 m

onth

s/tim

e T2

DM

and

, if t

reat

ed w

ith in

sulin

,

only

for 2

yea

rs o

r les

s

5 C

liffor

d RM

200

516

Frem

entle

Hos

pita

l, Fr

emen

tle

Aust

ralia

12

mo

6 w

eeks

/tim

e T2

DM

D

iabe

tes S

tudy

(FD

S)

6

Cho

e H

M 2

00517

U

nive

rsity

-affi

liate

d pr

imar

y

US

24 m

o 1

mon

th/ti

me

T2D

M, H

bA1c

leve

ls >

8.0%

ca

re in

tern

al m

edic

ine

clin

ic

7

Ode

gard

PS

2005

18

The

Uni

vers

ity o

f Was

hing

ton

US

6 m

o 1

wee

k/tim

e A

ged

≥ 18

yea

rs, T

2DM

, tak

ing

at

med

icin

e cl

inic

s

leas

t one

ora

l dia

bete

s med

icat

ion,

w

ith a

n H

bA1c

≥9%

8

Suks

ombo

on N

2005

19

Prim

ary

care

uni

t, Sa

mut

sako

rn

Thai

land

3

mo

3 m

onth

s/tim

e T2

DM

, 18-

60 y

ears

old

, tak

e O

AD

H

ospi

tal

as

met

form

in, g

lipiz

ide

and/

or

glib

encl

amid

e, H

bA1c

> 7

%

9 Su

ppap

itipo

rn S

200

520

Endo

crin

e cl

inic

in K

ing

Th

aila

nd

6 m

o 3

mon

ths/

time

T2D

M, a

ged

> 40

yea

rs

Chu

lalo

ngko

rn M

emor

ial

H

ospi

tal (

out p

atie

nts)

10

Ro

thm

an R

L 20

0521

U

nive

rsity

of N

orth

Car

olin

a

US

12 m

o 2-

4 w

eeks

/tim

e A

ged

>18

year

s old

, T2D

M, H

bA1c

G

ener

al In

tern

al M

edic

ine

leve

l >8.

0%, l

ife e

xpec

tanc

y >6

Pr

actic

e

mon

ths

11

Forn

os JA

200

622

Com

mun

ity p

harm

acie

s Sp

ain;

13

mo

1 m

onth

/tim

e tr

eatm

ent w

ith o

ral a

ntid

iabe

tics

Pont

eved

ra

for m

ore

than

2 m

onth

s

12

Scot

t DM

200

623

Siou

xlan

d C

omm

unity

Hea

lth

US

9 m

o 2

wee

ks/ti

me

T2D

M, a

ged

> 18

yea

rs

Cen

ter (

SCH

C)

Tabl

e 1. C

hara

cter

istic

s of t

he st

udie

s inc

lude

d in

the m

eta-

anal

ysis


No.

St

udy

Setti

ng

Cou

ntry

D

urat

ion

In

terv

entio

n In

clus

ion

of

stud

y fr

eque

ncy

crite

ria

13

K

rass

I 20

0724

C

omm

uniti

es p

harm

acie

s

Aust

ralia

6

mo

1 m

onth

/tim

e T2

DM

, HbA

1c ≥

7.5

%, t

akin

g at

leas

t

one o

ral g

luco

se lo

werin

g m

edica

tion

or

insu

lin, o

r HbA

1c ≥

7.0

%, t

akin

g at

leas

t

one o

ral g

luco

se lo

wer

ing

med

icat

ion

or

insu

lin, o

n at

leas

t one

anti-

hype

r-

tens

ive,

angi

na o

r lip

id-lo

wer

ing

drug

.

14

Elno

ur A

A 2

00825

A

l Ain

Hos

pita

l, gy

naec

olog

y

UA

E 6

mo

1 m

onth

/tim

e Pa

tient

pro

vide

d wi

thin

the fi

rst 20

wee

ks

outp

atie

nt cl

inic

s

of g

esta

tion,

dia

gnos

is o

f GD

M, a

nd

ag

ed 2

0- 3

9 ye

ars

15

Ph

umip

amor

n S

2008

26

Com

mun

ity h

ospi

tal i

n K

rabi

Th

aila

nd

10 m

o 2

mon

ths/

time

Mus

lim d

iabe

tic p

atie

nts,

aged

> 1

8

prov

ince

year

s, an

d H

bA1c

> 7

%

16

Pa

vasu

dthi

paisi

t A 2

00927

Dia

bete

s Clin

ic, O

ut-p

atie

nt

Thai

land

12

mo

6 m

onth

s/tim

e T2

DM

, HbA

1c le

vels

> 8.

0% w

ithou

t

depa

rtm

ent,

Non

gbua

lam

phu

m

acro

vasc

ular

com

plic

atio

ns

hosp

ital

17

D

ouce

tte W

R 20

0928

C

omm

unity

pha

rmac

y pr

actic

e site

US;

IOW

A

12 m

o 3

mon

ths/

time

T2D

M, H

bA1c

> 7

.0%

18

M

azro

ui N

RA 2

00929

Za

yed

Mili

tary

Hos

pita

l, ge

nera

l U

AE

12 m

o 4

mon

ths/

time

T2D

M, r

ecei

ving

ora

l hyp

ogly

caem

ic

med

ical

war

ds a

nd e

ndoc

rinol

ogy

th

erap

y

& m

edic

al o

utpa

tient

clin

ics

19

Tave

ira T

H 2

01030

Ve

tera

ns H

ealth

Affa

irs

US

22 m

o 4

wee

ks/ti

me

T2D

M, a

ged

> 18

year

s, or

HbA

1c 7%

-9%

w

ithin

the

prev

ious

6 m

onth

s

20

Ed

elm

an D

201

031

Vete

rans

Affa

irs M

edic

al C

ente

rs U

S; C

arol

ina

12.8

mo

2 m

onth

s/tim

e Pa

tient

s had

bot

h di

abet

es an

d hy

per-

& V

irgin

ia

tens

ion,

rec

eivi

ng m

edic

atio

n fo

r

diab

etes

, and

HbA

1c le

vel >

7.5%

and

hype

rten

sion

(SBP

>14

0 m

m H

g or

DBP

>90

mm

Hg)

21

M

ehuy

s E 2

01132

C

omm

unity

pha

rmac

ies

Belg

ium

6

mo

6 w

eeks

/tim

e T2

DM

, rec

eivi

ng o

ral h

ypog

lyca

emic

med

icat

ion

for a

t lea

st 12

mon

ths,

aged

45 –

75

year

s, BM

I> 2

5 kg

/m2,

and

regu

lar v

isito

r of p

harm

acy

22

Srira

m S

201

133

A p

rivat

e te

rtia

ry c

are

hosp

ital

Sou

th In

dia

8 m

o 3

mon

ths/

time

Indi

an, T

2DM

, age

d >

18 y

ears

, with

or

with

out o

ther

dise

ases

Tabl

e 1. C

hara

cter

istic

s of t

he st

udie

s inc

lude

d in

the m

eta-

anal

ysis

(con

t.)

N. Poolsup et al.22

No.

St

udy

Phar

mac

ist in

terv

entio

n U

sual

car

e

1 J

aber

LA

199

612

Dia

bete

s edu

catio

n, m

edic

atio

n co

unse

ling,

inst

ruct

ions

on

diet

ary

Con

tinue

d to

rece

ive

stan

dard

med

ical

car

e pr

ovid

ed b

y

regu

latio

n, e

xerc

ise, a

nd h

ome

bloo

d gl

ucos

e m

onito

ring,

and

th

eir p

hysic

ians

.

eval

uatio

n an

d ad

just

men

t of t

heir

hypo

glyc

emic

regi

men

.

2 G

uirg

uis L

M 20

0113

Usu

al c

are

plus

serv

ice

prov

ide;

dia

bete

s and

its c

ompl

icat

ion,

C

ontr

ol p

harm

acie

s pro

vide

d us

ual c

are,

phar

mac

ist

hypo

glyc

emia

, mon

itorin

g bl

ood

gluc

ose

leve

l, us

e of

off

ered

pat

ient

s som

e fo

rm o

f blo

od g

luco

se

bloo

d gl

ucos

e m

onito

r, nu

triti

on, e

xerc

ise, i

nsul

in u

se, i

nsul

in

met

er tr

aini

ng ,

othe

r tra

inin

g on

dia

bete

s man

agem

ent

de

vice

, med

icat

ion

use,

and

foot

car

e; a

nd te

achi

ng p

rovi

de;

(in-s

tore

cour

ses o

r con

tinui

ng e

duca

tion

cour

se).

ev

alua

ted

teac

hing

nee

ds, a

ddre

ssed

par

ticip

ant c

once

rns,

revi

ewed

blo

od g

luco

se le

vels,

revi

ewed

HbA

1c, m

easu

red

BP,

re

view

ed ch

oles

tero

l lev

els,

scre

ened

for m

icro

albu

min

uria

, rev

iew

ed

m

edic

atio

n pr

ofile

, adv

ised

on n

on-p

resc

riptio

n m

edic

atio

ns,

co

ntac

ted

phys

icia

n, co

ntac

ted

othe

r mem

bers

of d

iabe

tes t

eam

, and

met

er m

aint

enan

ce.

3 C

liffor

d RM

200

214 C

ompl

eted

a co

mpr

ehen

sive,

self-

dire

cted

revi

sion

of d

iabe

tes

Rece

ived

stan

dard

out

patie

nt c

are,

not c

ompl

eted

m

anag

emen

t prio

r to

the

stud

y, sa

w e

ach

patie

nt at

eve

ry v

isit,

and

the

patie

nt sa

tisfa

ctio

n su

rvey

.

co-o

pera

tion

with

the

diab

etes

phy

sicia

n an

d ot

her h

ealth

team

. 4

Sar

kadi

A 2

00415

Th

e ed

ucat

iona

l pro

gram

; a v

ideo

on

how

to “l

ive

wel

l” w

ith d

iabe

tes,

Usu

al c

are

and

assig

ned

to a

wai

ting

list o

f 2 y

ears

, the

n

exem

plify

ing

lifes

tyle

chan

ges m

ade

by th

ose

inte

rvie

wed

, a d

ice

gam

e th

ey w

ere i

nvite

d to

par

ticip

ate i

n th

e edu

catio

nal p

rogr

am.

w

here

que

stio

ns h

ad to

be

answ

ered

, and

a b

ookl

et o

r gui

de o

n

“how

to m

anag

e yo

ur d

iabe

tes”.

5 C

liffor

d RM

200

516 F

ace-

to-fa

ce m

eetin

g go

al-d

irect

ed m

edic

atio

n an

d lif

esty

le co

unse

ling,

H

ad a

stan

dard

ass

essm

ent b

y pr

imar

y ca

re p

hysic

ian.

te

leph

one

asse

ssm

ents

and

pro

visio

n of

oth

er e

duca

tiona

l mat

eria

l 6

Cho

e HM

200

517

Phar

mac

ists p

rovi

ded

eval

uatio

n an

d m

odifi

catio

n of

pha

rmac

othe

rapy

, Kep

t as a

nat

ural

cont

rol,

they

rece

ived

onl

y re

gula

r car

e

self-

man

agem

ent d

iabe

tes e

duca

tion,

and

rein

forc

emen

t of d

iabe

tes

incl

udin

g re

gula

r fol

low

up

visit

s with

thei

r prim

ary

care

co

mpl

icatio

ns sc

reen

ing p

roce

sses

thro

ugh

clini

c visi

ts an

d tel

epho

ne fo

llow-

up. p

hysic

ians

, rec

eive

d no

spec

ial c

onta

ct d

urin

g th

e

inte

rven

tion,

did

not

hav

e ex

it in

terv

iew

s or p

roce

ss

mea

sure

men

ts at

the

end

of th

e st

udy.

Tabl

e 2. D

etai

ls of

pha

rmac

ists’

inte

rven

tion

and

usua

l car

e of e

ach

tria

l


No.

St

udy

Phar

mac

ist in

terv

entio

n U

sual

car

e

7 O

dega

rd P

S 200

518

The

phar

mac

ist in

terv

entio

n w

as co

mpo

sed

of d

evel

opm

ent o

f a

Patie

nts w

ere

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ntin

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are

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abet

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re p

lan

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P), r

egul

ar p

harm

acist

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ient

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mun

icat

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on w

ith th

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rimar

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re p

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catio

n

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etes

care

pro

gres

s, ph

arm

acist

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vide

r com

mun

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on th

e sub

ject

’s wa

s not

pro

vide

d du

ring

the b

aseli

ne in

terv

iew

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oid

di

abet

es c

are

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ress

, and

DRP

. in

trodu

cing a

n in

terv

entio

n fo

r pat

ients

in th

e con

trol g

roup

. 8

Suk

som

boon

Se

lf-effi

cacy

trai

ning

pro

gram

by

mul

tidisc

iplin

ary

team

incl

udin

g

The

cont

rol g

roup

did

not

ent

er p

erce

ived

self-

effica

cy

N

200

519

phar

mac

ist, p

harm

acist

also

pro

vide

d ed

ucat

ion

on se

lf-ca

re b

ehav

iors

, tr

aini

ng p

rogr

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se

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cose

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kno

wle

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in d

iabe

tes.

9 S

uppa

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us d

iabe

tic d

rug

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, spe

cial

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ient

s wer

e in

terv

iew

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emog

raph

ic in

form

atio

n,

S

2005

20

med

icat

ion

cont

aine

rs.

bloo

d te

st, a

nd m

edic

al re

cord

s. 1

0 Ro

thm

an

Inte

nsiv

e ed

ucat

ion

sess

ions

, evi

denc

e-ba

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rithm

, pro

activ

e Pa

tient

s rec

eive

d us

ual c

are

from

thei

r prim

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care

RL 2

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m

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t. pr

ovid

er a

nd h

ad n

o fu

rthe

r man

agem

ent f

rom

the

dise

ase

man

agem

ent t

eam

. 1

1 Fo

rnos

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sual

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e pl

us p

harm

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llow

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(ind

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.

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pr

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m) w

hich

cons

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det

ectio

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an

d di

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invo

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thei

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n ca

re in

ord

er to

obta

in m

axim

um b

enefi

t fro

m th

e m

edic

atio

n. 1

2 Sc

ott

Patie

nt ed

ucat

ion

abou

t dise

ase,

testi

ng b

lood

glu

cose

leve

ls, d

rug

ther

apy,

Patie

nts r

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ved

stan

dard

dia

bete

s car

e an

d w

ere

DM

200

623

psyc

holo

gica

l adj

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ent i

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ptom

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- m

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y a

nurs

e.

glyc

emia

, hyp

ergl

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ia, a

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sis an

d co

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of a

ctio

n. 1

3 K

rass

I 20

0724

Se

rvic

es fr

om p

harm

acist

s inc

lude

d of

revi

ew o

f sel

f mon

itorin

g of

Th

e con

trol p

atien

ts ha

d tw

o vi

sits w

ith th

e pha

rmac

ist,

bl

ood

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ose;

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ase,

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icat

ion,

and

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styl

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ion;

adh

eren

ce

one

at th

e be

ginn

ing

and

one

at th

e en

d of

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stud

y.

supp

ort a

nd d

etec

tion

of d

rug-

rela

ted

prob

lem

s; an

d re

ferr

als t

o th

e

Dur

ing t

he in

terv

enin

g 6 m

onth

s, th

ey re

ceiv

ed ‘u

sual

care

’

patie

nts’

GPs

whe

n ap

prop

riate

. (

i.e. n

o sp

ecia

lized

dia

bete

s ser

vice

in th

e ph

arm

acy)

. 1

4 El

nour

En

sure

d th

at in

terv

entio

n pa

tient

s rec

eive

d ba

sed

trea

tmen

t and

Pa

tient

s rec

eive

d tr

aditi

onal

car

e: m

onth

ly cl

inic

visi

ts

A

A 2

00825

tr

eatm

ent f

or a

ny o

ther

conc

omita

nt il

lnes

s, ed

ucat

ed o

n G

DM

an

d se

lf-m

onito

ring

of p

lasm

a gl

ucos

e us

ing

diar

y ca

rds.

an

d its

man

agem

ent,

educ

atio

nal b

ookl

et, C

linic

al a

sses

smen

ts.

Tabl

e 2. D

etai

ls of

pha

rmac

ists’

inte

rven

tion

and

usua

l car

e of e

ach

tria

l (co

nt.)

N. Poolsup et al.24

No.

St

udy

Phar

mac

ist in

terv

entio

n U

sual

car

e

15

Phu

mip

amor

n

Usu

al c

are

plus

rem

inde

d th

e pa

tient

s, re

fille

d pr

escr

iptio

ns,

Patie

nts r

ecei

ved

usua

l sch

edul

e ca

re b

y pr

imar

y ca

re

S

2008

26

disc

usse

d th

e use

s of m

edic

atio

n, ch

eck

the p

ill co

unt,

educ

atio

n on

ph

ysic

ian

ever

y 4-

8 w

eeks

., di

spen

sing

by p

harm

acist

di

abet

es ab

out a

ppro

pria

te li

festy

le, co

rrec

t die

t, an

d pr

ovid

ed d

iabe

tic

fille

d an

d ga

ve g

ener

al a

dvic

e on

med

icat

ion

uses

ove

r

pam

phle

t; di

abet

ic co

mpl

icat

ions

, tar

get o

f tre

atin

g di

abet

es, l

ife st

yle

the

disp

ensa

ry co

unte

r on

a ro

utin

e ba

sis.

ch

ange

, and

dia

betic

med

icat

ions

. 1

6 Pa

vasu

dthi

paisi

t In

terv

entio

n gr

oup

rece

ived

inte

nsiv

e man

agem

ent f

rom

pha

rmac

ist

Patie

nts w

ere p

rovi

ded

care

by

thei

r phy

sicia

ns o

f int

erns

.

A

200

927

prac

titio

ners

; rec

eive

d an

asse

ssm

ent o

f med

icat

ion-

taki

ng ad

here

nce

an

d th

eir u

nder

stan

ding

of d

iabe

tes t

hen

appl

ied

algo

rithm

s for

m

anag

ing

gluc

ose

cont

rol a

nd o

ther

car

diov

ascu

lar r

isk fa

ctor

s. 1

7 D

ouce

tte

Disc

ussin

g m

edic

atio

ns, c

linic

al g

oals,

self-

care

activ

ities

with

pat

ient

s Pa

tient

s rec

eive

d us

ual d

iabe

tes c

are

from

thei

r prim

ary

WR

2009

28

and

reco

mm

endi

ng m

edic

atio

n ch

ange

s to

phys

icia

ns w

hen

appr

opria

te.

care

pro

vide

r. 1

8 M

azro

ui

The r

esea

rch

phar

mac

ist h

ad d

iscus

sions

with

thei

r phy

sicia

ns re

gard

ing

Patie

nts r

ecei

ved

norm

al c

are

from

med

ical

and

nur

sing

NRA

200

929

drug

ther

apy,

trea

tmen

t mod

ifica

tion,

edu

cate

d fo

r illn

ess a

nd

staff

, did

not

rece

ive

the

clin

ical

pha

rmac

y se

rvic

e.

med

icat

ion,

prin

ted

leafl

et, a

nd b

ehav

iora

l mod

ifica

tion.

19

Tave

ira

Usu

al c

are

plus

trea

tmen

t of h

yper

glyc

emia

, hyp

erte

nsio

n,

Patie

nts r

ecei

ved

the

stan

dard

car

e pr

ovid

ed b

y pr

imar

y

TH

201

030

hype

rlipi

dem

ia, a

nd ci

gare

tte sm

okin

g.

care

pro

vide

rs, f

requ

ency

aver

age

4 m

onth

s. 2

0 Ed

elm

an

Phar

mac

ist re

view

ed p

atie

nt m

edic

al re

cord

s, BP

, and

hom

e bl

ood

Pa

tient

s con

tinue

d to

rece

ive

thei

r usu

al p

rimar

y ca

re,

D 2

01031

gl

ucos

e re

adin

gs d

urin

g ea

ch se

ssio

n an

d de

velo

ped

indi

vidu

aliz

ed

no a

ctiv

e in

terv

entio

n.

plan

s for

med

icat

ion

or li

festy

le m

anag

emen

t. Ph

arm

acist

and

phys

icia

n

adju

sted

med

icat

ion

to m

anag

e ea

ch p

atie

nt H

bA1c

leve

l and

BP.

21

Meh

uys

Educ

atio

n ab

out T

2DM

and

com

plic

atio

ns, c

orre

ct u

se o

f ora

l Pa

tient

s rec

eive

d us

ual p

harm

acist

car

e.

E

2011

32

hypo

glyc

aem

ic a

gent

s, fa

cilit

atio

n of

med

icat

ion

adhe

renc

e, he

alth

y

lifes

tyle

edu

catio

n, a

nd re

min

ders

abo

ut a

nnua

l eye

and

foot

ex

amin

atio

ns.

22

Srira

m S

201

133

Patie

nts r

ecei

ved

phar

mac

eutic

al ca

re; m

edic

atio

n co

unse

ling

instr

uctio

ns P

atie

nts r

ecei

ved

usua

l dia

bete

s car

e.

on d

ieta

ry re

gula

tion,

exe

rcise

and

oth

er li

fest

yle

mod

ifica

tion.

Tabl

e 2. D

etai

ls of

pha

rmac

ists’

inte

rven

tion

and

usua

l car

e of e

ach

tria

l (co

nt.)


Effect on HbA1c

Twenty two trials involving a total of 2,808 diabetes patients were pooled. HbA1c levels at baseline, final assessment are presented in Table 4. HbA1c levels were significantly reduced with pharmacists’ interventions

compared with usual care. The pooled mean difference in the change of HbA1c was -0.68% (95%CI, -0.87% to -0.49%; p< 0.00001) (Figure 2). No publication bias was detected (Egger bias -0.35; 95% CI -2.89 to 2.19, P= 0.7785).

Table 3. Component of pharmacists’ intervention in individual trials

Education

Identifying and Study Materials provided

and counseling resolving drug-

related problems

Jaber LA 199612 - ✓ ✓ Guirguis LM 200113 glucose meter maintenance ✓ - Clifford RM 200214 - ✓ ✓ Sarkadi A 200415 video, booklet ✓ ✓ Clifford RM 200516 educational material ✓ ✓ Choe HM 200517 - ✓ ✓ Odegard PS 200518 - - ✓ Suksomboon N 200519 - ✓ - Suppapitiporn S 200520 booklet, containers ✓ - Rothman RL 200521 - ✓ - Fornos JA 200622 - ✓ ✓ Scott DM 200623 - ✓ ✓ Krass I 200724 monthly newsletter ✓ ✓ Elnour AA 200825 booklet ✓ ✓ Phumipamorn S 200826 pamphlet ✓ ✓ Pavasudthipaisit A 200927 - ✓ ✓ Doucette WR 200928 - ✓ ✓ Mazroui NRA 200929 leaflet ✓ - Taveira TH 201030 smoking cessation handout ✓ - Edelman D 201031 - ✓ ✓ Mehuys E 201132 educational material ✓ -

Sriram S 201133 leaflet, diabetic diet ✓ ✓ chart, diabetic diary

N. Poolsup et al.26

HbA1c (%)

Study Control Intervention

Baseline Final Baseline Final

Jaber LA 199612 11.5±2.9 12.1±3.3 12.2±3.5 9.2±2.1 Guirguis LM 200113 7.9* 7.1* 7.9* 6.9* Clifford RM 200214 8.5±1.6 8.1±1.6 8.4±1.4 8.2±1.5 Sarkadi A 200415 6.44* 6.60* 6.44* 6.09* Clifford RM 200516 7.1* 6.7* 7.5* 7.3* Choe HM 200517 10.2±1.7 9.3±2.1 10.1±1.8 8.0±1.4 Odegard PS 200518 10.6±1.4 9.2* 10.2±0.8 8.7* Suksomboon N 200519 9.73±1.88 10.23±2.59 9.03±1.67 8.69±1.82 Suppapitiporn S 200520 8.01±1.51 8.80±1.36 8.16±1.44 7.91±1.27 Rothman RL 200521 11±2 9.4* 11±3 8.5* Fornos JA 200622 7.8±1.7 8.5±1.9 8.4±1.8 7.9±1.7 Scott DM 200623 8.7* 8.0* 8.8* 7.08* Krass I 200724 8.3±1.3 8.0±1.2 8.9±1.4 7.9±1.2 Elnour AA 200825 6.87 6.55 6.85 6.38 (95%CI (95%CI (95%CI (95%CI 6.81, 6.93) 6.43, 6.67) 6.78, 6.90) 6.33, 6.42) Phumipamorn S 200826 8.7±1.6 8.1±1.9 8.7±1.5 7.9±1.4 Pavasudthipaisit A 201127 9.9±1.6 9.1* 9.8±1.4 7.8* Doucette WR 200928 7.91±1.91 8.03* 7.99±1.45 7.72* Mazroui NRA 200929 8.4 8.3 8.5 6.9 (95%CI (95%CI (95%CI (95%CI 8.6, 8.6) 8.1, 8.5) 8.3, 8.7) 6.7, 7.1) Taveira TH 201030 7.9±1.1 7.9* 8.1±1.5 7.2* Edelman D 201031 9.2±1.3 8.6* 9.2±1.5 8.3* Mehuys E 201132 7.3 ± 1.2 7.2 ± 1.0 7.7 ± 1.7 7.1 ± 1.1 Sriram S 201133 9.03 ± 0.46 8.31 ± 0.16 8.44 ± 0.29 6.73 ± 0.21

Data are mean±SD, * mean value

Table 4. HbA1c levels at baseline and final assessment reported in individual trials


DISCUSSION

Pharmacist is part of a multidiscip-linary team. This team normally consists of pharmacist, physician, nurse, technician, nutritionist, and other health care professions. All of the members in multidisciplinary team have important roles in diabetes management in achieving the goal of treatment, improving quality of life, controlling disease and its complications, delaying complication, and decreasing mortality and morbidity. Pharma-cists’ interventions are an important factor to improve glycemic control in diabetic patients. Pharmacists’ interventions include diabetes education and counseling on drug, disease, diet, exercise, life style modification, and self-management, assessment and adjustment of anti-diabetic medications, identifying and solving drug-related problems, co-operation with physician and other diabetes health care team, providing materials that reinforce patients to achieve a target goal, providing additional information on smoking cessation. All of these interventions aimed at improving glycemic control. In our study, HbA1c levels significantly reduced with pharmacists’ interventions compared with usual care. The pooled mean

difference in the change of HbA1c was -0.68% (95%CI, -0.87% to -0.49%; p< 0.00001). This reduction is the same as the ability in reducing HbA1c by taking some oral anti-hyperglycemic drugs for example, DPP-4 inhibitors and alpha-glucosidase inhibitors. This would help patients meeting the target of their treatment. To ensure that the meta-analysis included quality study, the Maastricht Amsterdam scale was used to assess the quality of individual study. The majority of the studies12-13, 15-20, 22-31,33 were rated as low quality, only three studies14, 21, 32 were of high quality. Most of these studies were open (not blinded) in study design. Performance bias in both intervention and control groups was likely in these trials as patients may seek other interventions to help control their blood glucose. This was evident when only high quality studies14, 21, 32 were pooled, showing a slight reduction in the effect of pharmacists’ interventions on HbA1c (mean difference -0.39%, 95% CI -0.61% to -0.17%, p = 0.0005). There were limitations in individual studies included in this meta-analysis. In most of the trials, both pharmacists and patients were not blinded and therefore,

Figure 2. Mean difference (95% confidence interval) of HbA1c between pharmacist intervention group and usual care group

N. Poolsup et al.28

contamination between groups was possible. This may affect the final outcomes. Secondly, Hawthorne effect may occur when study participants improved because of the only fact that they were participating in a research study. The findings of our study suggest several practice implications. First, pharma-cists’ interventions effectively improve glycemic control when compared with usual care; and thus, pharmacist should be part of a diabetes care team. Second, the approprite components of intervention should include both pharmacotherapy and non-pharmaco-therapy. Interventions on pharmacotherapy are screening and solving drug-related problems; if necessary, pharmacists provide feedback to physician, deliver patient education and counseling on medication. Non-pharmacotherapy interventions include education and counseling on diet, exercise, disease, adherence, and life-style modification.

CONCLUSION

The available evidence suggests that pharmacists’ interventions are more effective than usual care in decreasing HbA1c levels in diabetes patients. Pharmacists’ interventions included diabetes education and counseling on drug, disease, diet, exercise, life style modification, and self-management, an assessment and adjustment of anti-diabetic medications, identifying and solving drug-related problems, co-operation with physician and other diabetes health care team.

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