Impact of Pharmacist-Led Interventions to Improve Clinical Outcomes for Adults With Type 2 Diabetes at Risk of Developing Cardiovascular Disease: A Systematic Review and Meta-analysis

Abstract

Objective

The aim of this systematic review and meta-analysis of randomised controlled trials is to evaluate the impact of pharmacist-led interventions on cardiovascular disease (CVD) risk factors among patients with type 2 diabetes. Method: A literature review was conducted according to PRISMA guidelines using 4 electronic databases: Embase, MEDLINE, CINHAL and the Cochrane Central Register of Controlled Trials. We searched for pharmacist interventions among adults with type 2 diabetes and cardiovascular disease in randomised controlled trials from inception to May 2021 in primary care, diabetes clinics and hospitals. The clinical outcomes measured glycosylated haemoglobin (HbA1c), blood pressure (BP) and lipid profile. The non-clinical outcomes included medication adherence, smoking, health-related quality of life and the cost of the intervention. For the meta-analysis, clinical outcomes were pooled with the random effect model in RevMan 5.3. The Cochrane risk-of-bias tool was used to assess the quality of the included studies. Results: We retrieved 223 studies,141 of which were included in the review. Ten published articles met the inclusion criteria and were included in the meta-analysis. The pharmacists delivered the interventions alone or collaboratively with other healthcare professionals in hospitals or similar settings. The overall result showed a significant reduction in HbA1c (n = 10; standard deviation in mean value [SDM]: −.53%, 95% CI: −.84, −.23) and systolic BP (n = 10; [SDM]: −.35 mmHg, 95% CI: −.51, −.20) in pharmacist intervention groups. For the non-clinical outcomes, the review revealed variable results from pharmacist intervention compared with those standard care. Conclusion: Pharmacy interventions provide evidence for pharmacists’ decisive role in diabetes care management and reducing cardiovascular risk factors among adults with type 2 diabetes.

Keywords

type 2 diabetes cardiovascular disease clinical pharmacy intervention randomised controlled trials

Introduction

Diabetes mellitus (DM) is a chronic condition that can lead to complications and is increasing worldwide.¹ In addition, more than one-third of patients with T2D have a higher risk of mortality from CVD compared to those without diabetes.² Therefore, controlling the major risks for CVD, such as hypertension, dyslipidaemia and obesity, reduces long-term diabetes progression.³ Hypertension and T2D are commonly associated with diabetes because they share severe risk factors, such as insulin resistance, obesity and stress.⁴ As hypertension affects about 70% of people with diabetes,⁵ the appropriate management of HbA1c and cardiovascular risk factors can substantially reduce complications.⁶ However, despite published studies confirming that controlling statistics blood glucose levels reduces macrovascular and microvascular events, related to CVD risk factors among patients with T2D are alarming and remain poorly managed.⁷ According to the International Diabetes Federation (IDF), diabetes is a major expense for individuals, society and healthcare providers. In 2017, the accounted cost was USD 850 billion globally and the expenditure is estimated to increase by 12.7% in 2045.⁸ Even worse, the incidence of medication adherence ranged from 38% to 93%.⁹ However, intensivecomplex interventions and effective models of diabetes care are required to maintain tight clinical parameters, improve quality of life and decrease healthcare costs.

Several studies have highlighted the value-added by the pharmacist in chronic disease management,^10-12 for instance, improving diabetes care, CVD, hypertension and hyperlipidaemia.¹³ The role of pharmacists is more than dispensing medications; it has shifted from a product-centred approach to patient-centred care.¹⁴ Pharmaceutical care is defined as ‘the responsible provision of drug therapy to achieve definite outcomes which improve a patients’ quality of life’,¹⁵ and the care provided by the pharmacist is an essential element for patient health.¹⁶ The collaboration of pharmacists with other healthcare professionals to design, structure and implement a shared care plan is critical to ensure optimum health outcomes.^17,18 Pharmacists can also provide appropriate care through patient education and improve communication between pharmacists, healthcare teams and patients,¹³ when found to be acceptable by patients and physicians.¹⁸

Moreover, pharmacists’ knowledge of diabetes therapy and the relationship between pharmacists and patients during prescription refills build trust, promote good healthcare and help patients attain the required outcome.^19,20 Extensive international studies^10,17,18,21 have assessed the effectiveness of pharmacist-led interventions in supporting individuals with T2D and CVD. The components of the pharmacist interventions varied between the studies and are divided into 4 categories including:

• Educational interventions: educate patients about their condition and the medications offered by a pharmacist, nurse or other healthcare professional. The information is delivered to patients via phone, email, video and/or through individual or group sessions.²².

• Behavioural interventions: assist patients in changing their lifestyle and attitude, including advice on smoking, diet and exercise.²³

• Psychological interventions: work directly on mood states such as anxiety, depression and stress. They aim to increase problem-solving using cognitive approaches to change their behaviours.²⁴

• Clinical interventions: work directly towards improving the use of medications by solving drug-related problems, such as drug interactions, side effects and drug duplication issues.²⁵

Diabetes self-management education considers the pharmacist an integral part of designing curricula, delivering diabetes care and teaching self-management practices.²⁶

Diabetes and the Risk of Developing Cardiovascular Disease

Addressing CV risk factors in T2D patients is essential to avoid further complications such as coronary heart disease (CHD), stroke and myocardial infarction (MI).²⁷ While CVD is the principal cause to death, lowering HbA1c alone is not enough to prevent or delay diabetes progression.²⁸ Therefore, complex interventions are in high demand and include complex therapy regimens comprising diet, physical activity, smoking cessation. Treating T2D is complicated and a challenge for healthcare providers.²⁹ Nevertheless, such treatment is crucial in reducing diabetes complications and cardiovascular risk factors and improving clinical outcomes and quality of life. The effectiveness of self-management education and techniques are well documented by pharmacists.²³ Increasing patients' awareness and through education that focused on their illness, complications related to diabetes and medications adherence; they also need to be encouraged to promote lifestyle modification such as exercise and diet plan, which are keys to disease management.³⁰ In addition, self-monitoring of blood glucose is a crucial tool in controlling T2D.³¹ The purpose of this systematic review is to evaluate the impact of pharmacist-led interventions, in comparison with standard care, on HbA1c levels among patients with T2D and cardiovascular risk factors in primary care, diabetes clinics and hospitals.

Methodology

Search Strategy

We searched a comprehensive literature database using Embase, MEDLINE, CINAHL and Cochrane Central Register of Controlled Trials from inception to May 2020. The search terms included keywords and subject headings combined with Boolean operators: diabetes mellitus or diabetes mellitus type 2; cardiovascular disease or hypertension; clinical pharmacy or hospital pharmacist or pharmacy service or pharmaceutical care; and randomised control trials.

Inclusion and Exclusion Criteria

Studies were included in the review if they did the following: (1) they were RCT with comparable groups (pharmacist care compared to standard care groups); (2) they evaluated the impact of pharmaceutical care delivered by pharmacists either independently or in collaboration with the healthcare team; (3) the intervention was conducted mainly in hospitals, primary care clinics or diabetic clinics; (4) they targeted adults with T2D and hypertension or cardiovascular risk factors (compared to standard care); (5) they reported 2 or more clinical indicators, including HbA1c, SBP, DBP, fasting blood glucose, lipid profiles (LDL-C, HDL-C, TG and total TC), BMI and smoking and other outcomes, including medication adherence, health-related quality of life, 10-year CHD risk and the cost-effectiveness of the interventions; and (6) the full article was published in the English language. The exclusion criteria were non-English publications, conference papers, protocols and practice guidelines.

Study Selection

Data were extracted independently by 2 reviewers, who screened all titles, abstracts and full articles that were retrieved from the electronic databases. The full-text articles were obtained through the University of Bradford’s catalogue and open sources. The reviewers read the full papers independently before they were included, and any disagreement was solved by discussion.

Data Extraction and Synthesis

Each reviewer extracted the following data: (1) study characteristics (study design, setting, sample size, duration of follow-up and year); (2) characteristics of patients (uncontrolled T2D HbA1c >7% (53 mmol/mol) with modifier cardiovascular risk factors); (3) characteristics of interventions (including education, medication consultation, self-care assessment, intervention delivered by a pharmacist only or with other healthcare providers); (4) characteristics of the standard care group; and (5) clinical indicator measurements (including HbA1c, BP and lipid profile from the baseline to the end of the intervention).

Risk-of-bias Assessment

The Cochrane tool for assessing the risk of bias was used to evaluate the quality of the individual included studies.³² The risk of bias identifies the following criteria: random sequence generation, concealment of allocation, the blinding of participants and personnel, the blinding of the outcome assessment, selective reporting and other sources of bias. Due to the nature of delivering the intervention for the included studies, the healthcare personnel could not be blinded. For each factor, the bias risk was rated as low, unclear or high. Two reviewers double-checked this assessment, and any disagreements were discussed until a consensus was reached.

Data Analysis

Statistical analyses were conducted following the recommendations of the Cochrane guidelines. For continuous data, the SBP, HbA1c and LDL-C results were pooled in a meta-analysis. Review Manager 5.3 (RevMan) software was used to analyse and produce forest plots using a random-effects model due to clinical heterogeneity across the studies. The heterogeneity of the studies was assessed using I² and the P-value.

Results

Study Characteristics

As shown in Figure 1, a total of 448 studies were identified from the electronic database searches. After screening the titles and abstracts, 141 potentially relevant studies were assessed for eligibility, with ten studies being identified as meeting the inclusion criteria. The excluded articles and reasons for exclusion are stated. The included studies were RCTs in different settings and countries that targeted patients who had been diagnosed with T2D and had CVD and cardiovascular risk factors. Participants were followed up in hospitals, primary care clinics, diabetic clinics or health centres. Out of ten studies, 5 were conducted in North America (United States), 2 in the Middle East (United Arab Emirates and Jordan), 2 in Asia (Hong Kong and Singapore) and 1 in Europe (Cyprus). The included studies’ characteristics are presented in Table 1.

Figure 1.

Flow diagram of the literature search process (PRISMA 2009 Flow Diagram).

Table 1.

Pharmacist Interventions Studies Characteristics.

Title/author/year	Type of study/setting/time	Populations	Interventions	Outcomes
Al-Mazroui et al., 2009³⁵	-RCT	234 T2D with hypertension age > 18 years HbA1c > 7%	Pharmacists discussed with physicians regard changing patients’ medicines if needed. The clinical pharmacist taught patients about 1- diabetes conditions and medications. 2- Behaviour modification and self-monitoring. 3- Reinforced medication adherence and smoking cessation. 4- Supplementary pamphlet information about hypertension and hyperlipidaemia	Clinical outcomes: BP, HbA1c, fasting blood glucose, lipid profile (LDL-C, TG and TC) and BMI Humanistic outcomes: Health-related quality of life, diabetes knowledge, medication adherence and 10-year CHD risk
	-Zayed military hospital
	-UAE			Economics outcome: N/A
	-12 months			Economics outcome: N/A
Chan et al., 2012³³	-Prospective RCT	105 T2D High risk of CVD	Face-to-face interview (15–30 minutes) before each physician visit including 1-Recorded medication history. 2- Evaluated medicine adherence 3- education on CVD and lifestyle modification. 4- Identified drug-related problems. 5- Recalled patients’ medication by placing colour stickers on their pillbox	Clinical outcomes: BP, HbA1c, LDL-C, HDL-C, triglyceride level and urinary albumin to creatinine ratio
	-Diabetic clinic of Tung Wah Eastern hospital	105 T2D High risk of CVD
	-Hong Kong	Age > 18 years HbA1c ≥ 8%		Humanistic outcomes: CHD risk, stroke risk, medication adherence and diabetes knowledge economic outcome: Cost
	-9 months	Age > 18 years HbA1c ≥ 8%
Cohen et al., 2011⁴²	-RCT	99 T2D	Four weeks 2 hours sessions, each session had 2 parts. The first session lasted 40–60 minutes delivered by the multidisciplinary team about lifestyle modification. The second part delivered by the pharmacist focused on 1- treatment for diabetes, hypertension and hyperlipidaemia. 2- Discussion about individual risk	Clinical outcomes: BP, HbA1c and LDL-C. Humanistic outcomes: Diabetes self-care score and health-related quality of life
	-Veterans affairs hospital	HbA1c > 7%
	-U.S.	LDL > 100 mg/dl or LDL > 70 for those with coronary artery disease	Booster sessions occurred monthly for 5 months (90 minutes) discussion focused on group needs	Economics outcome: N/A
	-6 months	BP>130/80 mmHg		Economics outcome: N/A
Edelman et al., 2010⁴⁰	-RCT	239 and T2D with hypertension	1- Pharmacist and physician-reviewed patients medical records, BP and home blood glucose reading. 2- Developed plans for medication and lifestyle management tailored to each patient. 3- Education sessions run by pharmacists and nurses on medications and lifestyle lasted 90–120 minutes	Clinical outcomes: BP and HbA1c
	-Veteran affairs medical centre	Age > 18 years HbA1c ≥ 7.5% BP > 140/90		Humanistic outcomes: Medication adherence and self-efficacy
	-U.S.	LDL-C > 100 mg/dl		Economic outcome: Healthcare utilisation cost
	-12 months	LDL-C > 100 mg/dl		Economic outcome: Healthcare utilisation cost
Jarab et al.,2012³⁶	-RCT	156 T2D	Clinical pharmacist delivered: 1- Education about type 2 diabetes, risk, complications and prescribed medications. 2- Ensure patients receive evidence therapy for diabetes, hypertension and dyslipidaemia and problems related to drugs. 3- Emphasised lifestyle management. 4- Booklet on medication prepared to support education. Then 8 weekly telephone calls follow-up with patients	Clinical outcomes: BP, HbA1c and lipid values. Humanistic outcomes: Diabetes self-care score and medication adherence
	-Royal medical service hospital	156 T2D
	-Jordan	Age > 18 years HbA1c > 7.5%		Economics outcome: N/A
	-6 months			Economics outcome: N/A
Title/author/year	Type of study/setting/time	Populations	Interventions	Outcomes
Korcegez et al., 2017³⁴	-RCT	152 patients T2D	Face-to-face interview with pharmacist including 1- explained the importance of self-monitoring blood glucose, lifestyle modification. 2- Education on diabetes, medications and self-care activities. 3- Discussion on treatment plan and recommendations. 4- Reviewed prescribed medicines and identified drug-related problems such as side effects. 5- Education supported by pamphlets containing information on T2D, complications, treatment goals and self-care	Clinical outcomes: BP, HbA1c, fasting blood glucose, lipid profile (HDL-C, LDL-C, triglycerides and total cholesterol), body mass index (BMI) and waist circumference
	-Public hospital outpatient diabetes clinic	152 patients T2D		Humanistic outcomes: Self-care activities and medication adherence
	-Northern Cyprus	HbA1c > 7%		Economic outcome: N/A
	-12 months	HbA1c > 7%		Economic outcome: N/A
Rothman et al., 2005³⁷	-RCT	194 T2D with CV risk factors	Intensive diabetes management included 1- intensive education and counselling on diabetes and medications management. 2- Telephone contact every 2-4 weeks follow-up. 3- Provided evidence-based treatment algorithms to reduce cardiovascular risk factors and improve the glycaemic level. 4- Addressing issues related to health behaviour and health education. 5- Supported in additional intervention may require by patients	Clinical outcomes: BP, HbA1c and total cholesterol levels
	-Academic general internal medicine practice (University of North Carolina)	Age ≥ 18 years HbA1c ≥ 8%		Humanistic outcomes: Diabetes knowledge, treatment satisfaction, adverse events and aspirin use
	-U.S.	Life expectance > 6 months		Economic outcome: Use of clinical services
	-12 months	Life expectance > 6 months		Economic outcome: Use of clinical services
Siaw et al., 2017³⁹	-Prospective, open-label, parallel-arm, randomised controlled	330 High-risk patients age ≥ 21 years	The physician assessed the patients and referred them to a diabetes nurse educator for self-care counselling or dietitian for dietary counselling, followed up with the clinical pharmacist. The clinical pharmacist delivered face-to-face sessions lasting for 20–30 minutes every 4–6 week about 1- adjusting medications using SIGN algorithm. 2- providing prescriptions 3- telephone follow-up	Clinical outcomes: BP, HbA1c, LDL-C and TG Humanistic outcomes: Problems area of diabetes (PAID) and diabetes treatment satisfaction (DTSQ)
	-4 outpatient healthcare institutions	HbA1c > 7%		Economic outcome: Diabetes-related health service utilisation rates and costs
	-Singapore	Polypharmacy multiple comorbidities
	-6 months
Taveira et al., 2010⁴¹	-RCT	109 T2D with cardiovascular risk factors	Four weeks 2 hours sessions, each session had 2 parts. The first session lasted 40–60 minutes delivered by a multidisciplinary team focused on diabetes self-care (diet and physical activities). The second part lasted 60–90 minutes delivered by the clinical pharmacist about 1- diabetes, hypertension and dyslipidaemia treatment. 2- Discussion on diabetes risk factors and smoking cessation	Clinical outcomes: BP, HbA1c and fasting lipids non-HDL-C and LDL-C)
	-Veterans affairs hospital	109 T2D with cardiovascular risk factors		Humanistic outcomes: Diabetes self-care score and tobacco use
	-U.S.	Age > 18 years HbA1c > 7%- 9%		Economics outcome: N/A
	-4 months	Age > 18 years HbA1c > 7%- 9%
Wu et al., 2018³⁸	-RCT	214 T2D with cardiovascular risk factors	Group medical visits were held once weekly for 4 weeks, followed by 4 booster sessions every 3 months. 2-hour sessions delivered by clinical pharmacist including 1- educational on diabetes self-care. 2- Behaviour counselling and medicine management for diabetes, hypertension and dyslipidaemia. 3- Diabetes self-management	Clinical outcomes: BP, HbA1c and LDL-C Humanistic outcomes: UKPDS risk score and health-related quality of life
	-Three Veterans Health Administration hospitals	Age > 18 years HbA1c > 7%
	-U.S.	Age > 18 years HbA1c > 7%		Economic outcome: Healthcare cost
	-13 months	BP > 130/80 mmHg LDL > 100 mg/dl		Economic outcome: Healthcare cost

Abbreviations: BP, Blood pressure; CVD, Cardiovascular disease; CHD, Coronary heart disease.

Description of Included Studies and Type of Intervention

The interventions were delivered by the pharmacist either directly^33-36 or collaboratively with other healthcare professionals, such as a specialist nurse, diabetes educator or dietitian.^37-42 The follow-up duration ranged from 4 to 13 months. The nature of the pharmacist intervention for each study is presented in detail in Table 1.

Quality of Included Studies

The risk-of-bias assessment varied among the included studies, as illustrated in Figure 2. All studies used adequate methods for randomisation, and 9 studies contained insufficient information about allocation concealment. No participants were blinded to the intervention due to the nature of the research. Blinding the outcome assessment was discussed, and incomplete outcome data were reported as low risk because an intention-to-treat analysis was used in all studies. The outcomes were unclear in 2 studies, and other biases testified as an unclear risk in 9 studies.

Figure 2.

Cochrane risk-of-bias tool for randomised controlled trials.

Study Outcomes Measures

All the studies considered HbA1c as an outcome for their interventions.^33-42 The mean value of HbA1c at the baseline was 8% across the studies. The pooled analysis indicated that the intervention group showed a significant reduction in HbA1c (SMD −.53, 95%; CI: −.84, −.23) (Figure 3A). However, 6 studies reported a positive effect and 3 a slight improvement associated with pharmacist care. Whereas 1 study revealed no difference between the groups (95%; Cl: −1.88, −1.32).⁴³ It was noted that T2D patients with HbA1c >8.5% greatly benefited from pharmacist intervention, as it reduced by .3%–1.6% (95%; Cl: –1.88,–1.32).

Figure 3.

Pooled results (meta-analyses). (A) Meta-analysis HbA1c. (B) Meta-analysis SBP. (C) Meta-analysis LDL-C.

Three studies analysed fasting blood glucose.^34–36 Korcegez et al.³⁴ found an improvement in fasting blood glucose in the intervention group compared to the control group (intervention group –1.7 mmol/L, control group –1.3 mmol/L). Al-Mazroui et al.³⁵ and Jarab et al.³⁶ reported a significant reduction in the intervention group compared to the control (intervention group –3.01 mmol/L, control group –.78 mmol/L). (intervention group –2.3 mmol/L, control group +.9 mmol/L), respectively. The pooled analysis revealed a significant reduction under pharmacist care compared to standard care (standardised mean difference –.61 mmol/L, 95%; CI: –.78,–.43).

Systolic blood pressure (BP) was measured in all studies. In total, 9 studies revealed a significant reduction in SBP in the intervention group at the end of the research in contrast to Wu study.³⁸ Pooled analysis indicated a significant reduction in the intervention compared to the control group (SMD −.35 mmHg 95%; CI: −.51, −.20) (Figure 3B). Seven studies also measured the diastolic 36 blood pressure and reported a reduction of approximately 2.8 mmHg in the intervention group. Pooled results indicated a significant reduction with the intervention group (SMD −.57 mmHg 95%; CI: −.69, .45).

Lipid profiles levels varied across the studies. LDL-C measurements were found in 8 studies.^33-39,41,42 The pooled analysis reported nonsignificant results between both groups (SMD −.17 mmol/L; 95% CI: −.39, .04) (Figure 3C). Four studies measured HDL-C, and the pooled result showed (SMD −.01 mmol/L; 95% CI: −.09, .06). Triglyceride (TG) levels were measured in 4 studies revealed no significant difference between groups (SMD .39 mmol/L; 95% CI: −.84, .07). In total, 5 studies reported total cholesterol (TC).^33,34,36,41 The pooled analysis estimated a significant reduction in the intervention group compared to the control group (SMD –.45 mmol/L, (95% CI: –.79, –.12).

Four studies measured the body mass index (BMI).^33-35,41 The mean value of BMI was lowered by 1 kg/m2 from the baseline to the endpoint in the intervention groups. At the same time, the BMI value increased by .4 kg/m2 in the control groups. pooled analysis documented a reduction under pharmacist care (standarised mean difference –.26 kg/m2 ; 95% Cl: –.41, –.1).

The United Kingdom Prospective Diabetes Study (UKPDS) risk engine, CHD risk and stroke risk scores were found in 4 studies. They calculated the estimated risk factors in T2D patients. The CHD score was reported in 2 studies^33,35 using Framingham, British National Formulary and a validated cardiac risk score that is specific to the Hong Kong population. Both results showed a statistically significant reduction in CHD risk scores during the study in the intervention group compared to the control group. In addition, the stroke risk score in the intervention group decreased.³³ Finally, UKPDS was recorded in 1 study.³⁸ The mean change in the UKPDS coronary events risk was reduced significantly in both the intervention and control groups.

Medication adherence was assessed in 6 studies^33-36,40,42 and measured using the Morisky self-reported scale. There was no difference in medication adherence between the groups in the 2 studies.^36,40 Two studies^34,35 used the Morisky–Green test and self-reported adherence questionnaires and found a significant increase in pharmacotherapy adherence in the intervention group. One study used a medication possession ratio and found an insignificant difference between the comparison groups.⁴² A final study³³ used an equation to calculate medication adherence, which improved the compliance score following intervention to 96.0% compared to the control group at 84.1%. An additional one⁴² reported nonsignificant results with medication possession ratio. Pooled analysis indicated a significant results with pharmacist intervention group (SMD 18.14%, 95% CI; [13.05, 23.23]).

Three studies^33,35,37 demonstrated the level of diabetes knowledge regarding the purpose of using medicines in T2D. The studies showed improvement by 20% in diabetes knowledge for patients who received the pharmacist intervention (SMD 55.68%, 95% CI; [33.67, 77.68]).

The health-related quality of life was reviewed in 3 studies^35,38,42 using the SF-36 questionnaire. There was no difference between the 2 groups in the 2 studies.^38,42 The mean change was −.02 + .9 vs −.4 + .09 and 2.13(95% Cl) vs 2.73 (95% Cl), respectively. The third study³⁵ reported improved health-related quality scores with the intervention patients, whereas those in the control group remained unchanged. Pooled results scores were SMD .15, 95% CI; [−.22, .51] for physical and SMD 1.35, 95% CI; [.55, 2.16] for mental.

Diabetes self-care scores were reported in 4 studies.^34,36,41,42 Diabetes self-care comprised diet, physical activity, self-management of blood glucose (SMBG) and foot care. The studies noted a slight improvement in the intervention group compared to the control group in the overall score. One study revealed that the total self-efficacy score was significant with the pharmacist interventions SMD 1.6, 95% CI; [.9, 2.4]. The 3 studies observed a slight improvement of 2 to 3.8 out of 5 points in the intervention group compared to the control. The achievement was mostly in diet, SMBG and foot care. Pooled results were SMD .24 [−.06, .54] for general diet, SMD .26, 95% CI; [.06, .45] for physical activity, SMD .31, 95% CI; [.08, .54] for SMBG and, SMD .69, 95% CI; [−.32, 1.70] for foot care.

Cost calculations were reported in 4 studies.^33,38-40 Pharmaceutical care was found to be more cost-effective in 3 studies. Furthermore, there was an incremental reduction in healthcare utilisation for the patients under pharmacist care compared to standard care (USD 4220 ± 31 091 vs 5752 ± 29 690),³⁸ USD 5,086 for preventing CHD events,³³ and (USD 516.77 ± 222.1 vs 607.78 ± 268.39) for outpatient diabetes-related care³⁹; and (USD 460 vs 504) for education sessions,⁴⁰ respectively.

Discussion

This systematic review demonstrated that pharmaceutical care programmes positively influence clinical parameters, health-related quality of life and health costs when T2D is poorly controlled. The pharmaceutical care programmes in the identified studies focused on 3 fundamental concepts:

(1) -Medication management included reviewing medicines, explaining drug-related problems, monitoring therapy progress, adjusting dosage and optimising administration.

(2) -Disease management included education, counselling and using evidence-based care algorithms.

(3) -Advice on lifestyle modification, such as self-care practice skills and training, self-management education and encouragement on a healthy diet and smoking cessation.

Despite the diversity in pharmacist-led interventions, they all aimed to improve the clinical outcomes and quality of life among patients with diabetes. The pharmacist interventions were delivered in 2 ways, either individually or in group sessions, performed by pharmacists only or with the healthcare team collaboratively.

Reduction in HbA1c, lower BP and better lipid profiles were associated with pharmacist involvement in patient education, consultation and follow-up. Previous systematic reviews demonstrated a similar reduction in HbA1c for intervention groups.^44,45 Moreover, every 1% reduction in HbA1c is associated with a 14% decrease in MI, a 12% decrease in the risk of stroke and a 37% decrease in microvascular complications.⁴⁶ Notably, patients with HbA1c greater than 8.5% gain more benefit from the pharmaceutical intervention programmes because they have the highest risk of cardiovascular disease.⁴⁷

Included studies focused on SBP as a critical risk factor in T2D. The results revealed that every 1 mmHg elevation in SBP is associated with a 2% increase in the risk of hyperglycaemia⁴⁸ and every 10 mmHg reduction in SBP is associated with a 12% CV risk reduction; with the lowest risk occurring at an SBP less than 120 mmHg.⁴⁹ Similar to our finding, another systematic review⁵⁰ reported a reduction in the diastolic BP by −3.9 mmHg in patients under pharmacist care.

LDL-C is related to insulin resistance and is the strongest predictor of CHD development, followed by HDL-C.⁵¹ Our pooled estimate showed a significant reduction in TC associated with pharmaceutical care equivalent to reviews conducted by Machado et al.⁵² and Charrois et al.⁵³

The role of the clinical pharmacist in diabetes self-management was demonstrated to be positive.⁵⁴ A previous review mentioned that lifestyle consultation might reduce cardiovascular disease by 50%.⁵⁵ Another analysis indicated that medication adherence was enhanced with the education provided by the pharmacist, including discussion issues related to patients’ therapy.¹³ Similar to Jamshed’s findings,⁵⁶ our review suggests that pharmacist intervention is cost-effective. A significant improvement in BMI was also shown in our study. Impressive results were previously reported by Bukhsh et al.⁵⁷ Pharmacists have the opportunity to play a fundamental role in managing diabetes and its complications by directing patients to monitor their therapy to improve medication adherence and provide counselling and advice on lifestyle issues for improving quality of life. This systematic review suggests that pharmacist interventions can lead to relatively more significant improvements in glycaemic control when comparing T2D interventions among all healthcare professionals (Shamala Ayadurai, 2020, Pousinho et al., 2020).

The strength of the review was randomised controlled trials conducted in the same setting (hospitals). Direct pharmacist-led interventions and pharmacist-collaborative interventions are both highlighted to be effective models in diabetes management. The study’s limitations were as follows: a small number of patients enrolled; self-reported questionnaire responses may have been affected by social desirability and recall bias; there may have been variation in education programmes for the patients; and limited studies reported the cost of the pharmacist-led intervention.

The limitations with the systematic review were that many results were reported in different units, making it hard to pool out the results. In addition, there were variations in the study design and the way of conducting the intervention, causing the level of information delivered to individuals not at the same standard.

Our study emphasises the influential role of pharmacists in diabetes care. Delivering pharmacist interventions among T2D patients supports the patients’ knowledge of diabetes and delays long-term complications, and it also assists in medication adherence and motivates lifestyle modification. Although HbA1c and BP often share risk factors, controlling them with a lipid profile is essential in reducing CVD in the future.

Overall, the randomised controlled trials conducting in the same setting (hospitals), included provide a comprehensive review of pharmacist interventions consisting of patients cousneslling and education on T2D and it is complications, and advice on medication adherence revealed that pharmacist interventions associated with a significant improvement in clinical outcomes, medication adherence, diabetes knowledge and health-related quality of life outcomes when compared with standard care. Direct pharmacist-led interventions and pharmacist-collaborative interventions both highlighted to be effective model in diabetes management. The limitation was the variation reported results, small number of patients enrolled in the studies, self-reported questionnaire responses may have been affected by social desirability and recall bias, no education programme for the patients and limited studies reported the cost of the pharmacist-led intervention.

Conclusion

This systematic review and meta-analysis emphasise the effect of pharmaceutical care programmes in minimising the risk factors associated with T2D. The studies documented an overall improvement in glycaemic control, lipid profiles, BP levels and BMI with various pharmacist-led interventions. Increasing medication adherence and lifestyle modifications were also reported. Future research should evaluate smoking cessation in reducing CVD risk and investigate the cost-effectiveness of pharmacist intervention in hospital settings for T2D patients. The most effective elements of pharmacist-led interventions have been not identified. Ultimately, numerous studies in different countries have documented the satisfaction of pharmacist interventions for T2D patients with CVD risk factors. Moreover, this systematic review suggests that well-trained clinical pharmacists can assist other healthcare professionals in improving diabetes care.

Footnotes

Acknowledgements

I am sincerely thankful to my supervisors Dr. Jonathon and Professor Anne for their support and providing me with the opportunity to write this paper. I am also thankful to MORG group especially Kristina to help me with the assessment of risk bias.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Rahma M. Alabkal

References

American DiabetesA . Diagnosis and classification of diabetes mellitus. Diabetes Care. 2012;35(suppl l):S64-S71.

Sarwar

Gao

Seshasai

, et al. Emerging Risk Factors Collaboration. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: A collaborative meta-analysis of 102 prospective studies. Lancet. 2010;375(9733):2215-2222.

Martín-Timón

Gao

Seshasai

SRK

, et al.

Type 2 diabetes and cardiovascular disease: Have all risk factors the same strength?

World J Diabetes. 2014;5(4):444-470.

UK Prospective Diabetes Study Group UKPDS . Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group. BMJ. 1998;317(7160):703-713.

Lago

Singh

Nesto

. Diabetes and hypertension. Nat Clin Pract Endocrinol Metab. 2007;3(10):667.

UKPDS UPDSG . Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ Br Med J. 1998;317(7160):703-713.

Low Wang

Hess

Hiatt

Goldfine

. Clinical update: cardiovascular disease in diabetes mellitus atherosclerotic cardiovascular disease and heart failure in type 2 diabetes mellitus – mechanisms, management, and clinical considerations. Am Heart Assoc, 2016;133(24):2459-2502.

Cho

Shaw

Karuranga

, et al. IDF diabetes atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract. 2018;138:271-281.

Krass

Schieback

Dhippayom

. Adherence to diabetes medication: A systematic review. Diabet Med. 2015;32(6):725-737.

10.

Hughes

Wibowo

Sunderland

Hoti

. The role of the pharmacist in the management of type 2 diabetes: Current insights and future directions. Integr Pharm Res Pract. 2017;6:15-27.

11.

George

Molina

Cheah

Chan

Lim

. The evolving role of the community pharmacist in chronic disease management-a literature review. Ann Acad Med Singapore. 2010;39(11):861-867.

12.

Tan

ECK

Stewart

Elliott

George

. Pharmacist services provided in general practice clinics: a systematic review and meta-analysis. Res Soc Adm Pharm. 2014;10(4):608-622.

13.

Lindenmeyer

Hearnshaw

Vermeire

Van Royen

Wens

Biot

. Interventions to improve adherence to medication in people with type 2 diabetes mellitus: A review of the literature on the role of pharmacists. J Clin Pharm Ther. 2006;31(5):409-419.

14.

Toklu

Hussain

. The changing face of pharmacy practice and the need for a new model of pharmacy education. J Young Pharm. 2013;5(2):38-40.

15.

Hepler

Strand

. Opportunities and responsibilities in pharmaceutical care. Am J Hosp Pharm. 1990;47(3):533-543.

16.

Salgado

Moles

Benrimoj

Fernandez-Llimos

, Pharmacists’ interventions in the management of patients with chronic kidney disease: A systematic review. Nephrol Dial Transplant. 2012;27(1):276-292.

17.

Alhabib

Aldraimly

Alfarhan

. An evolving role of clinical pharmacists in managing diabetes: evidence from the literature. Saudi Pharm J. 2016;24(4):441-446.

18.

Wubben

Vivian

. Effects of pharmacist outpatient interventions on adults with diabetes mellitus: A systematic review. Pharmacotherapy. 2008;28(4):421-436.

19.

Wermeille

Bennie

Brown

McKnight

. Pharmaceutical care model for patients with type 2 diabetes: Integration of the community pharmacist into the diabetes team–a pilot study. Pharm World Sci. 2004;26(1):18-25.

20.

Omboni

Caserini

. Effectiveness of pharmacist’s intervention in the management of cardiovascular diseases. Open Heart. 2018;5(1):e000687.

21.

Ojieabu

Bello

Arute

. Evaluation of pharmacists’ educational and counselling impact on patients’ clinical outcomes in a diabetic setting. J Diabetes. 2017;8(1):7-11.

22.

Hörnsten

Lundman

Stenlund

Sandström

. Metabolic improvement after intervention focusing on personal understanding in type 2 diabetes. Diabetes Res Clin Pract. 2005;68(1):65-74.

23.

Maranda

Lau

Stewart

Gupta

. A novel behavioral intervention in adolescents with type 1 diabetes mellitus improves glycemic control: Preliminary results from a pilot randomised control trial. Diabetes Educ. 2015;41(2):224-230.

24.

Steed

Cooke

Newman

. A systematic review of psychosocial outcomes following education, self-management and psychological interventions in diabetes mellitus. Patient Educ Couns. 2003;51(1):5-15.

25.

Knez

Duggan

Laaksonen

Nijjar

. Evaluation of clinical interventions made by pharmacists in cancer services. Pharm J. 2008;280(7492):277-280.

26.

Beck

Greenwood

Blanton

Bollinger

, et al. National standards for diabetes self-management education and support. Diabetes Educ. 2017;43(5):449-464.

27.

Abdul-Ghani

DeFronzo

Del Prato

Chilton

Singh

Ryder

REJ

. Cardiovascular disease and type 2 diabetes: has the dawn of a new era arrived? Diabetes Care. 2017;40(7):813-820.

28.

International Diabetes Federation . Diabetes and cardiovascular disease. Brussels, Belgium; 2016.

29.

Morgan

. Challenges and opportunities in managing type 2 diabetes. Am Health Drug Benefits. 2017;10(4):197-200.

30.

Erhardt

. Rationale for multiple risk intervention: The need to move from theory to practice. Vasc Health Risk Manag. 2007;3(6):985-997.

31.

Schnell

Hanefeld

Monnier

. Self-monitoring of blood glucose: A prerequisite for diabetes management in outcome trials. J diabetes Sci Technol. 2014;8(3):609-614.

32.

Higgins

JPT

Altman

Gøtzsche

, et al. The cochrane collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011:343:d5928.

33.

Chan

Siu

S-C

Wong

CKW

, et al. A pharmacist care program: Positive impact on cardiac risk in patients with type 2 diabetes. J Cardiovasc Pharmacol Ther. 2012;17(1):57-64.

34.

Korcegez

Sancar

Demirkan

. Effect of a pharmacist-led program on improving outcomes in patients with type 2 diabetes mellitus from Northern cyprus: a randomised controlled trial. J Manag Care Spec Pharm. 2017;23(5):573-582.

35.

Al Mazroui

Kamal

Ghabash

Yacout

Kole

McElnay

. Influence of pharmaceutical care on health outcomes in patients with Type 2 diabetes mellitus. Br J Clin Pharmacol. 2009;67(5):547-557.

36.

Jarab

Alqudah

Mukattash

Shattat

Al-Qirim

. Randomized controlled trial of clinical pharmacy management of patients with type 2 diabetes in an outpatient diabetes clinic in Jordan. J Manag Care Pharm. 2012;18(7):516-526.

37.

Rothman

Malone

Bryant

, et al. A randomised trial of a primary care-based disease management program to improve cardiovascular risk factors and glycated hemoglobin levels in patients with diabetes. Am J Med. 2005;118(3):276-284.

38.

Taveira

Jeffery

Jiang

Tokuda

Musial

, et al. Costs and effectiveness of pharmacist-led group medical visits for type-2 diabetes: A multi-center randomised controlled trial. PLoS One. 2018;13(4):e0195898.

39.

Siaw

MYL

Malone

, et al. Impact of pharmacist-involved collaborative care on the clinical, humanistic and cost outcomes of high-risk patients with type 2 diabetes (IMPACT): A randomised controlled trial. J Clin Pharm Ther. 2017;42(4):475-482.

40.

Edelman

Fredrickson

Melnyk

, et al. Medical clinics versus usual care for patients with both diabetes and hypertension: A randomised trial. Ann Intern Med. 2010;152(11):689-696.

41.

Taveira

Friedmann

Cohen

, et al. Pharmacist-led group medical appointment model in type 2 diabetes. Diabetes Educ. 2010;36(1):109-117.

42.

Cohen

Taveira

Khatana

SAM

Dooley

Pirraglia

W-C

. Pharmacist-led shared medical appointments for multiple cardiovascular risk reduction in patients with type 2 diabetes. Diabetes Educ. 2011;37(6):801-812.

43.

Michiels

Bugnon

Chicoye

Dejager

Moisan

Allaert

F-A

, et al. Impact of a community pharmacist-delivered information program on the follow-up of type-2 diabetic patients: a cluster randomized controlled study. Adv Ther. 2019;36(6):1291-1303.

44.

Yaghoubi

Mansell

Vatanparastc

Steeves

Zeng

Farag

. Effects of pharmacy-based interventions on the control and management of diabetes in adults: a systematic review and meta-analysis. Can J Diabetes. 2017;41(6):628-641.

45.

Van Eikenhorst

Taxis

van Dijk

de Gier

. Pharmacist-led self-management interventions to improve diabetes outcomes. A systematic literature review and meta-analysis. Front pharmacol. 2017;8:891.

46.

Stratton

Adler

Neil

, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): Prospective observational study. BMJ. 2000;321(7258):405-412.

47.

Laakso

. Glycemic control and the risk for coronary heart disease in patients with non- insulin-dependent diabetes mellitus: the finnish studies. Ann Intern Med. 1996;124(1 Pt 2):127-130.

48.

Aikens

Zhao

Saleheen

Reilly

Epstein

Tikkanen

, et al. Systolic blood pressure and risk of type 2 diabetes: A mendelian randomisation study. Diabetes. 2017;66(2):543-550.

49.

Stratton

Adler

Neil

, et al. Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): Prospective observational study. BMJ. 2000;321(7258):412-419.

50.

Santschi

Chiolero

Colosimo

, et al. Improving blood pressure control through pharmacist interventions: A meta-analysis of randomised controlled trials. J Am Heart Assoc. 2014;3(2):e000718.

51.

Solano

Goldberg

. Lipid management in type 2 diabetes. Clin Diabetes. 2006;24(1):27-32.

52.

Machado

Nassor

Bajcar

Guzzo

Einarson

. Sensitivity of patient outcomes to pharmacist interventions. part III: systematic review and meta-analysis in hyperlipidemia management. Ann Pharmacother. 2008;42(9):1195-1207.

53.

Charrois

Zolezzi

Koshman

, et al. A systematic review of the evidence for pharmacist care of patients with dyslipidemia. Pharmacotherapy. 2012;32(3):222-233.

54.

Shah

Chan

Nguyen

Bhatt

. Enhancing diabetes care by adding a pharmacist to the primary care team. Am J Health Syst Pharm. 2013;70(10):877-886.

55.

Gæde

Vedel

Larsen

Jensen

GVH

Parving

H-H

Pedersen

. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med. 2003;348(5):383-393.

56.

Jamshed

Siddiqui

Rana

Bhagavathula

. Evaluation of the involvement of pharmacists in diabetes self-care: a review from the economic perspective. Front Public Health. 2018;6(244):244.

57.

Bukhsh

Khan

Lee

SWH

Lee

L-H

Chan

K-G

Goh

B-H

. Efficacy of pharmacist based diabetes educational interventions on clinical outcomes of adults with type 2 diabetes Mellitus: a network meta-analysis. Front Pharmacol. 2018;9:339.