Volume 27 Number 2

Key messages

• This study assessed the feasibility, safety and preliminary impact of pharmacist-led, multidisciplinary care to reduce cardiometabolic risk in adults with type 2 diabetes who have diabetic foot ulcers and metabolic syndrome, using a prospective single-arm pilot design.
• The intervention included a pharmacist-delivered medication review, biweekly counseling, lifestyle education and ADR monitoring embedded in routine clinic care for a high-risk DFU+MetS population at a tertiary hospital.
• Recruitment and retention met feasibility thresholds (45.1% and 89.1% at 6 months). Pre–post analyses showed improved adherence (MARS-10 6.8→8.5), better cardiometabolic measures (HbA1c 8.5%→8.0%; SBP 144→137mmHg; LDL-C 126→115mg/dL), and favorable wound outcomes (95.9% stable; 51.0% healed; median healing 13 weeks), with mostly mild–moderate ADRs supporting the need for larger controlled trials.

Introduction

Diabetes mellitus is a cluster of metabolic disorders characterised by persistent hyperglycemia resulting from either beta cell destruction, impaired insulin sensitivity or both.¹ With the global diabetes burden reaching 537 million people, diabetic foot ulcers (DFUs) have become increasingly prevalent, affecting 19 to 34 percent of individuals with diabetes as a major complication of long-standing or poorly controlled disease.² A recent study by Unnikrishnan et al³ reported that approximately two-thirds of newly diagnosed type 2 diabetes patients in India fall into the very high cardiovascular risk category. Nearly all require lipid lowering therapy and half require antihypertensive therapy, highlighting the need for early and aggressive management. Metabolic syndrome (MetS) further amplifies this burden. It is independently associated with increased cardiovascular disease risk, and the likelihood of adverse events rises with both the number and combination of MetS components.⁴ Recent evidence demonstrates that pharmacists can meaningfully contribute to cardiovascular risk reduction.⁵ Pharmacist-led programs such as the Malaysian Diabetes Medication Therapy Adherence Clinic (DMTAC) have shown significant improvements in glycemic control and reduced complications related to diabetic foot, along with better cardiovascular risk profiles.⁶  Despite this evidence, there is limited research specifically examining pharmacist-led interventions in patients who have both DFU and MetS, a combination that places individuals at particularly high cardiometabolic risk. This study seeks to address this gap by evaluating feasibility, refining and validating study tools, and exploring preliminary trends in clinical and adherence outcomes. This pilot study was intentionally designed to assess feasibility indicators and generate early outcome signals rather than to test efficacy or establish causal effects.

Materials and methods

Study design and setting

This prospective observational cohort study was designed to assess the feasibility of recruitment strategies, evaluate the study tools, and gather preliminary outcome data for pharmacist-led interventions aimed at managing cardiovascular risk in patients with diabetic foot ulcers (DFU) and metabolic syndrome (MetS).^7,8 The study was conducted from December 2024 to May 2025 in the specialised diabetic foot clinic of a tertiary care hospital in Erode, Tamil Nadu. It was not intended to determine causal effects; instead, it focused on assessing feasibility parameters including recruitment, retention, data completeness, tool reliability and acceptability.

Ethical approval

Ethical approval was obtained from the Institutional Ethics Committee of JKKN College of Pharmacy (JKKNCP/IEC-CER/1926125/Ph.D) before study initiation. All procedures adhered to the principles of the Declaration of Helsinki.⁹ Written informed consent was obtained from all participants, with verbal explanations provided for those with low literacy to ensure accessibility.

Participants

Eligible participants had a confirmed diagnosis of type 2 diabetes with active DFU (University of Texas (UT) classification system) and MetS, defined by ATP III criteria as having three or more of the following: waist circumference >102cm (men) or >88cm (women), triglycerides ≥150mg/dL, HDL cholesterol <40mg/dL (men) or <50mg/dL (women), blood pressure ≥130/85mmHg, or fasting glucose ≥100mg/dL.¹⁰ Participants were required to be on complex medication regimens (≥3 medications for diabetes, hypertension, or dyslipidemia) and were receiving care for diabetes and cardiovascular risk management. Exclusion criteria included severe comorbidities, such as advanced renal or hepatic disease, inability to provide informed consent, unlikelihood of completing follow-up (for example, due to relocation or severe mobility issues), or enrollment in other interventional studies. Over two months (October–November 2024), 122 patients were screened during routine clinic visits using electronic medical records and physician referrals, with 55 (45.08%) meeting the eligibility criteria and being enrolled.

Intervention

The intervention was delivered by a clinical pharmacist in collaboration with a multidisciplinary team comprising endocrinologists, podiatrists, nurses and cardiologists, and was integrated into routine clinical care. It included comprehensive medication reviews to optimise therapies for glycemic control, hypertension, dyslipidemia, and antiplatelet agents, guided by American Diabetes Association standards.¹¹ Biweekly 30–45 minute counselling sessions for six months employed motivational interviewing, pill boxes and journals to enhance adherence, and lifestyle education regarding dieting, exercising, quitting smoking and controlling weight. Standard protocols and referrals assessed ADRs. Intervention fidelity exceeded 80% and participant satisfaction reached 85%, confirming the feasibility.

Study tools

Study parameters were assessed using validated tools. DFU severity was evaluated with the Texas Wound Classification (grades 0–3, stages A–D), with wound size measured via digital planimetry and healing defined as complete epithelialisation. Both systems demonstrated high inter-rater reliability (kappa >0.80).¹² Cardiovascular risk was assessed using the 2008 Framingham 10-year CVD Risk Score, which incorporates age, sex, cholesterol levels, blood pressure, smoking status and diabetes status.¹³ Medication adherence was measured with the 10-item Medication Adherence Report Scale (MARS-10, score 0–10, ≥8 indicating high adherence), validated for chronic conditions (Cronbach’s alpha >0.75), supplemented by pharmacy refill records and patient self-reports.¹⁴ ADRs were documented using the Indian Pharmacopoeia Commission’s ADR reporting form (Version 1.4), capturing details such as reaction description, severity and causality.¹⁵ Tools were administered at baseline, 3 months, and 6 months, with 90% of participants reporting the MARS-10 as easy to complete.

Outcomes

Primary outcomes focused on feasibility, including recruitment rate (45.08%, target ≥40%), retention (target ≥80% at sixmonths), tool validation (e.g., ≤10% missing data, kappa ≥0.8 for DFU grading), medication adherence changes (MARS-10 scores), and clinical stability (no worsening of DFU grade).¹⁴ Secondary outcomes included changes in blood pressure (target <130/80mmHg), LDL cholesterol (<100mg/dL), HbA1c (<7%), DFU healing (≥50% wound size reduction or complete healing), and ADR incidence. Exploratory outcomes included DFU healing time and changes in Framingham risk scores. Data were collected prospectively, with adverse events reported immediately to ensure participant safety.

Data collection and analysis

Data were collected using electronic health records, standardised forms, and hospital laboratory assays at baseline, three months, and six months, with follow-up assessments during routine clinic visits. Descriptive statistics summarised baseline characteristics (means ± SD for continuous variables, frequencies for categorical variables). Changes in continuous outcomes (such as HbA1c, blood pressure) were analysed using paired t-tests, while categorical outcomes (such as adherence categories) were analysed with McNemar’s test, with a significance level of p<0.05. No imputation was applied for missing data, which was anticipated to be <5%, and complete case analysis was used. All statistical analyses were conducted using IBM SPSS Statistics for Windows, Version 27.0 (IBM Corp., Armonk, NY, USA). The results informed the design of a potential full-scale randomised controlled trial, such as refining exclusion criteria to enhance recruitment.

Results

Participant flow and recruitment

Between December 2024 and May 2025, 122 patients were screened for eligibility to participate. A total of 67 were excluded due to severe comorbidities (n=25), inability to provide informed consent or cognitive impairment (n=15), non-adherence history or <3 Medications (n=12), pregnancy or life-threatening disease (n=8), and for other reasons such as relocation or physical difficulties (n=7). Fifty-five patients (45.1%) were recruited, achieving the recruitment target (≥40%). Baseline measures were completed for all participants. At the 3-month follow-up, 52 (94.5%) responded, and at the 6-month follow-up, 49 (89.1%) responded, exceeding the threshold for retention (≥80%). Attrition was due to relocation, family issues, work conflicts, transportation difficulties and loss to follow-up. Recruitment and retention results are described in Figure 1.

 

Figure 1. Participant flow and feasibility outcomes

 

Baseline characteristics

Mean participant age was 59.3±10.8 years, with 20 (36.4%) females. Most were from middle-income families (52.7%) and had primary (40%) or secondary education (45.5%). Their occupations were retired (34.5%), skilled (32.7%), unemployed (20.0%) and professional (12.7%). Mean diabetes duration was 7.5±4.6 years, and DFU duration was 11.4±11.2 weeks. DFU staging was A (40%), B (36.4%), C (14.5%), and D (9.1%). Mean wound size was 4.5±3.9 cm-sq; infection signs were present in 58.2% and deep wounds in 30.9%.

Determinants of lifestyle included: active smokers (21.8%); former smokers (18.2%); occasional alcohol users (21.8%); and regular alcohol users (7.3%). Mean physical activity duration was 2±1.3 hours/week. Commonly seen comorbidities were hypertension (27.3%), coronary artery disease (23.6%), peripheral vascular disease (21.8%), retinopathy (20%), depression (21.8%), and chronic kidney disease (18.2%). All participants met the ATP III criteria for MetS, with a mean waist circumference of 113±15cm, triglycerides of 182±48mg/dL, HDL cholesterol of 40±8mg/dL, blood pressure of 144±21/82±11mmHg, and fasting glucose of 179±48mg/dL. Thirty-five (63.6%) were in the high CVR category per the Framingham 10-year score. Baseline characteristics are in Table 1.

 

Table 1. Baseline characteristics of participants (N = 55)

 

Feasibility outcomes

Recruitment was 45.1%, and 6-month retention was 89.1%, both within the feasibility threshold range. Data completeness was >95%, DFU grading reliability was high (kappa=0.85), and intervention fidelity was >92%. Participant satisfaction was 3.6±1.1 (scale 1–5).

Clinical and adherence outcomes

Medication adherence improved significantly: mean MARS-10 score increased from 6.8±1.9 to 8.5±1.3 (p<0.001), with high adherence rising from 60.0% to 81.6% (p=0.002). HbA1c decreased from 8.5±1.4% to 8.0±1.3% (p<0.001). Systolic BP fell from 144±21 to 137±20mmHg (p=0.003), diastolic BP from 82±11 to 79±10mmHg (p=0.012), and LDL cholesterol from 126±33 to 115±30mg/dL (p<0.001). Proportions achieving therapeutic targets improved for HbA1c <7% (25.5% to 42.9%), BP<130/80mmHg (29.1% to 44.9%), and LDL <100mg/dL (30.9% to 46.9%).

DFU stability was ensured in 95.9% of cases. Complete recovery was seen in 51%, and 85.7% had ≥50% reduction in wound size. Mean wound size decreased from 4.5±3.9 to 1.4±2.1cm-sq (p<0.001). The median healing time was 13 weeks (95% CI, 10.4–15.6). Safety monitoring revealed 22 ADRs (55% mild, 32% moderate, 14% severe). Hospitalisation was reported in 21.8% of participants, and 14.5% experienced serious adverse events. Detailed outcomes are tabulated in Table 2.

 

Table 2. Clinical, adherence and safety outcomes

 

Exploratory outcomes

The Framingham 10-year cardiovascular risk improved, with the high-risk prevalence declining from 63.6% at baseline to 44.9% at 6 months (p=0.004). Waist circumference decreased from 113±15 to 110±14cm (p=0.004), and BMI decreased from 31.8±5.2 to 30.7±5kg/m-sq (p<0.001). Fifteen participants (30.6%) achieved a weight reduction of 5% or more. These exploratory findings are summarised in Table 3. A visual summary of key clinical outcomes is provided in Figure 2, illustrating reductions in HbA1c, blood pressure, LDL cholesterol, waist circumference and BMI from baseline to six months.

 

Table 3. Exploratory Outcomes (n=49 Completers)

 

Figure 2: Changes in key clinical outcomes between baseline and six months. Values represent mean measurements for participants completing follow-up (n=49). Improvements were observed in HbA1c, systolic and diastolic blood pressure, LDL cholesterol, waist circumference and body mass index.

 

Discussion

This prospective cohort study assessed the effects of pharmacist-led interventions on individuals with type 2 diabetes, diabetic foot ulcers (DFUs), and metabolic syndrome (MetS), demonstrating the study’s feasibility, acceptable retention rates, and high fidelity in intervention implementation.^16–18 Participant recruitment was strong, data completeness was strictly maintained, and DFU grading was valid, with a predominance of participants having long-standing diabetes, which is associated with increased cardiometabolic risk. Marked improvements were observed in medication adherence, with rates increasing from 60% at baseline to over 80% at the six-month evaluation. Concurrent with this improvement, statistically significant reductions were recorded in HbA1c, blood pressure, and LDL cholesterol, with a higher proportion of participants achieving therapeutic targets. DFU outcomes were favorable, with over 95% ulcers remaining stable, half or more achieving complete healing, and a majority recording significant decreases in wound surface area, with a median time to healing of 13 weeks. Exploratory analyses revealed decreases in cardiovascular risk factors, waist circumference and BMI, with nearly a third of participants achieving a weight loss of 5%, indicating widespread cardiometabolic benefits from pharmacist input. Even modest reductions in waist circumference and BMI are clinically meaningful in individuals with metabolic syndrome. Such changes correlate with improved insulin sensitivity, reduced inflammatory burden, and lower cardiovascular risk, all of which are particularly relevant in patients with diabetic foot ulcers.

These results suggest a potential contribution of pharmacists to optimising chronic disease management, although causality cannot be inferred in this single-arm feasibility study. Enhanced adherence is a key factor in maintaining glycemic control and preventing complications. Improvements in metabolic markers and DFU healing outcomes may indicate a potential contribution of pharmacist involvement, although these trends must be interpreted cautiously given the single arm design and lack of a comparator group.^16,19,20 Progressive reductions in HbA1c are in accordance with those from larger-scale meta-analyses. DFU healing rates are comparable to those from studies in diabetic foot care where pharmacist input is implemented, highlighting the linkage between their professional contribution and high-risk populations.^{16–18,20,21} No withdrawals were in direct relationship with adverse events, and ADRs and hospitalisations recorded were in accord with expectations for advanced diabetic patients with numerous comorbidities.¹⁸ Proactive medication review and educational interventions conducted by pharmacists likely contributed to the early detection and prevention of drug-related issues, in addition to supporting available evidence for medication safety through their involvement.^22,23

The strengths of the study include its prospective design, stringent confirmation of endpoints, and the incorporation of pharmacy services as part of a multidisciplinary practice. This study has several limitations. As a small, single-center, non-randomised pilot, the findings are not generalisable and cannot be interpreted as evidence of effectiveness. The single-arm design precludes causal inference, and improvements may reflect regression to the mean, natural healing trajectories or unmeasured confounders. The short follow-up period and potential selection bias may also have influenced outcomes. These limitations are characteristic of feasibility studies and support the need for a full-scale randomised controlled trial.

In general, the findings rationalise the engagement of pharmacists as key members of interdisciplinary diabetes care teams, particularly for people with coexisting DFU and MetS. The intervention could be scaled up, as patient acceptability was high, and salient benefits were observed in adherence, clinical and exploratory endpoints. These findings should inform the optimisation of pharmacist-led interventions for individuals with high-risk chronic diseases. Further studies should involve multicenter, randomised controlled trials to establish the effectiveness, sustainability and economic viability of pharmacist-led care, as well as qualitative studies to determine the facilitators and deterrents of pharmacist-led care in various healthcare system contexts.²⁴

In our investigation, pharmacist interventions were found to be safe, comprehensive, and feasible in high-risk subjects, positioning the pharmacist in a primary role in diabetes care.^16‑18

Conclusion

This pilot study demonstrates that pharmacist-led interventions for individuals with type 2 diabetes, diabetic foot ulcers and metabolic syndrome are feasible to implement within a multidisciplinary setting. Recruitment and retention goals were met and tools were reliable. Preliminary trends showed improvements in adherence, cardiometabolic control, and ulcer outcomes; however, due to the small, single-center, non-randomised design, these findings cannot be interpreted as causal. The study provides essential groundwork for designing larger multicenter randomised controlled trials to evaluate clinical effectiveness, cost implications and long-term sustainability.

Declaration

Ethics approval and consent to participate

Ethical approval for this study was granted by the Institutional Review Board of JKKN College of Pharmacy (JKKNCP/IEC-CER/1926125/PhD). Written informed consent was obtained from all participants before their inclusion in the study. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments, or with comparable ethical standards.

Consent for publication

Individual consent for publication was obtained from all participants involved in the study. Participants were informed that the data collected would be used for research and potential publication, ensuring confidentiality and anonymity in the presentation of the research findings.

Data availability statement

The datasets generated and analysed during the current study are not publicly available due to patient confidentiality and institutional restrictions. However, de-identified data may be shared by the first author upon reasonable request, subject to ethical approval.

Conflict of interest

The authors declare no conflicts of interest

Funding

This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.

Acknowledgements

The authors sincerely thank all the patients who participated in this study and the staff of the Diabetic Foot Clinic in Erode for their cooperation and support. They are deeply grateful to Dr R Suresh, Associate Professor in the Department of Pharmacy at Annamalai University, for his constant guidance, constructive feedback, and encouragement throughout this work. We also acknowledge the valuable collaboration of the multidisciplinary team, comprising endocrinologists, podiatrists, nurses and cardiologists. We also thank the Institutional Ethics Committee of JKKN College of Pharmacy for their guidance and approval.

Authors contributions

SS: Study concept and design, acquisition of data: analysis and interpretation of data, drafting of the manuscript, and statistical analysis.

GP: Critical revision of the manuscript, statistical analysis, administrative, technical or material support and study supervision.

Orcid IDs

Satheesh S: 0000-0001-7179-1143
Praveena G: 0000-0002-0302-6965

Author(s)

Satheesh S¹, Praveena G*² M.Pharm, PhD

¹Research Scholar, Faculty of Pharmacy, Karpagam Academy of Higher Education, Tamil Nadu, India
²Department of Pharmacognosy, Karpagam Academy of Higher Education, Tamil Nadu, India

*Corresponding author email praveena.g@kahedu.edu.in

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