Shambo Samrat Samajdar, Department of Diabetes and Allergy-Asthma Therapeutics Specialty Clinic, Kolkata, India
Rohan Tripathi, Inovocare Healthsoft Solutions, Kolkata, India.
Shatavisa Mukherjee, School of Tropical Medicine, Kolkata, India.
Kaushik Biswas, Medica Superspeciality Hospital, Kolkata, India.
Shashank R Joshi, Joshi Clinic, Mumbai, Maharashtra, India.
Sougata Sarkar, Calcutta School of Tropical Medicine, Kolkata, India.
Santanu K Tripathi, JIMS Hospital and Medical College, Hospital, Indore, India.
Bharat Saboo, Prayas Diabetes Center, Indore, India.
Abstract
Background:
The complexity of managing type 2 diabetes (T2D) in the elderly is compounded by the need to balance over-prescription, under-prescription, and appropriate prescription. Managing hyperglycemia and its complications, along with geriatric syndromes such as cognitive impairment and falls, often leads to use of an increased number of medications. Quality improvement measures, while aimed at better management, can inadvertently contribute to the burden of polypharmacy. Addressing medication non-adherence is crucial, as it is a significant contributor to poor clinical outcomes, increased hospitalizations, and healthcare costs.
Objectives:
This study thus aimed to evaluate the effectiveness of interventions to improve medication adherence among elderly patients with T2D. It assessed the impact of a medication adherence device, clinical pharmacological intervention, and their combination compared to standard of care (SOC) alone on adherence rates, adverse drug reactions (ADRs), and glycemic control.
Materials and Methods:
This pilot study was a factorial randomized controlled trial. A total of 120 elderly T2D patients with a medication adherence rate of less than 80% over the past year were randomized into four groups: (1) medication adherence device + SOC, (2) clinical pharmacological intervention + SOC, (3) combined intervention + SOC, and (4) SOC alone. The primary outcome was medication adherence, assessed through pill counting. ADRs were evaluated using the Naranjo ADR causality assessment scale, and glycemic control was monitored through HbA1c levels. Statistical analyses included chi-square tests and ANOVA, with significance set at P < 0.05.
Results:
Interim analysis showed the highest adherence rate in the combined intervention group (82.1%), followed by the clinical pharmacological intervention + SOC group (75.3%), the medication adherence device + SOC group (73.1%), and the SOC alone group (70.0%). The combined intervention group also recorded the lowest ADR rate (6.6%). Regarding glycemic control, 81% of the combined intervention group achieved an HbA1c level of less than 7%, compared to 80% in the clinical pharmacological intervention + SOC group, 78% in the medication adherence device + SOC group, and 69% in the SOC alone group. Differences in glycemic control were not statistically significant (P = 0.950).
Conclusions:
The study indicates that combined interventions including medication adherence devices along with SOC significantly improve medication adherence and reduce ADRs in elderly T2D patients. Future research should focus on diverse populations and long-term sustainability of these interventions.
Introduction
Type 2 diabetes (T2D) represents a significant and growing global health challenge, particularly with population aging worldwide. The prevalence of T2D among adults is projected to increase from 9.3% in 2019 to an estimated 10.9% by 2045, highlighting the urgency for effective management strategies, especially among the geriatric population.[1] This demographic trend is set against a backdrop of increasing healthcare costs, with an estimated $760 billion spent globally on diabetes management in 2019 alone.[2]
The elderly, especially in countries like India, are particularly vulnerable to challenges associated with T2D management, such as polypharmacy and potentially inappropriate prescription.
Polypharmacy, defined as the use of multiple medications, is common in older adults, with reports indicating that 57%–59% of community-dwelling older adults in the United States use five or more medications weekly.[3] Polypharmacy and hyperpolypharmacy are significant concerns in India, particularly among the older adult population. Recent studies have shown that approximately 49% of older Indian adults practice polypharmacy, which is defined as the use of multiple medications, and 31% practice hyperpolypharmacy, indicating an even more extensive use of medications (95% confidence interval: 42–56; P < 0.01 for polypharmacy and 21–40; P < 0.01 for hyperpolypharmacy). Additionally, the use of potentially inappropriate medications (PIMs) is alarmingly high, affecting approximately 28% of this demographic (95% confidence interval: 24–32; P < 0.01).[4] These statistics underscore the urgent need for promoting rational geriatric prescription practices in India to address these growing healthcare concerns. This situation often leads to medication non-adherence, a significant hurdle in achieving effective disease control and minimizing health complications.[5]
This study is designed to address these challenges. It aims to explore innovative approaches to enhance medication adherence in elderly patients with T2D. Such approaches are critical, given that older adults with diabetes are at a higher risk of polypharmacy than those without diabetes.[6,7]
The complexity of managing T2D in the elderly is compounded by the need to balance over-prescription, under-prescription, and appropriate prescription. A hypothetical scenario of a 79-year-old female with multiple comorbidities could result in a regimen of 12 different medications, taken in 19 doses per day.[8] This complexity underscores the necessity for guidance beyond standard clinical practice guidelines. Polypharmacy in elderly diabetic patients not only concerns the number of drugs prescribed but also concerns the nature of these medications. Managing hyperglycemia and its complications, along with geriatric syndromes such as cognitive impairment and falls, often leads to use of an increased number of medications. Quality improvement measures, while aimed at better management, can inadvertently contribute to the burden of polypharmacy.[8]
Addressing medication non-adherence is crucial as it is a significant contributor to poor clinical outcomes, increased hospitalizations, and healthcare costs.[9] In light of these challenges, this study aims to evaluate the effectiveness of medication adherence tools and clinical pharmacological reconciliation in elderly T2D patients, comparing these interventions with standard care in terms of improving adherence rates and assessing their impact on adverse drug reactions (ADRs) and glycemic control.
Materials and Methods
Study design:
This pilot study is a factorial randomized controlled trial conducted to evaluate the effectiveness of various interventions aimed at improving medication adherence among elderly patients with type 2 diabetes (T2D). The study is stratified into four groups: medication adherence device + standard of care (SOC), clinical pharmacological intervention + SOC, combined intervention (medication adherence device + clinical pharmacological intervention) + SOC, and SOC alone (control group). The duration of interventions is 6 months, with an emphasis on assessing both the short-term and long-term impacts of the interventions.
Participants:
The study includes elderly patients aged over 60 years, diagnosed with T2D, and currently on oral antidiabetic agents. Eligibility criteria also include a medication adherence rate of less than 80% over the past 12 months. The study excluded patients with conditions or on treatments that could significantly interfere with the study outcomes. In total, 120 participants were enrolled, with 30 participants allocated to each of the four study arms.
Intervention groups:
Participants were randomly assigned to one of the four groups. The interventions included the use of a medication adherence device, clinical pharmacological intervention, or a combination of both, in addition to the standard care provided to all participants. The control group received standard diabetes care without additional interventions.
Clinical pharmacological intervention:
The clinical pharmacological intervention (CPI) implemented in this study was designed to optimize medication use and improve clinical outcomes in elderly T2DM patients. This intervention, provided by a specialized clinical pharmacologist, comprised a comprehensive bundle known as clinical pharmacological reconciliation, review, and feedback (CPRRF).[10] The key components of CPRRF included evaluating the necessity and appropriateness of prescribed medications; deprescribing unnecessary, redundant, contraindicated, or poorly tolerated medicines; and identifying medication errors during transitions of care. The intervention also involved tailoring dosages to individual patient needs; preventing, minimizing, and managing ADRs; and enhancing treatment adherence. Additionally, the intervention considered the affordability and availability of medications to improve adherence; individualized treatment plans to accommodate patient-specific factors; rationalized polypharmacy, particularly in the elderly; and aimed to enhance the overall quality of life. Clinical pharmacological reconciliation review and feedback were utilized by a trained clinical pharmacologist who had used tools like Beer’s criteria,[11] medication appropriateness index,[12] calculator, and personal expertise to rationalize prescription with polypharmacy. This multifaceted approach was integral in ensuring safe, effective, and patient-centered diabetes management.
The duration of interventions in the study is 6 months, with an emphasis on assessing both the short-term and long-term impacts of the interventions.
Short-term: any acute ADR prevention.
Long-term: 6 months, any critical issues on adherence and long-term glycemic control and safety issues with patients.
Medication adherence device
MedpeR®: your personal Medicinal helpeR by Inovocare Healthsoft Solutions Pvt. Ltd., is a unique smart pillbox with vigilant consumption tracking through app and web support, which does not need 24-h Wi-Fi connection, developed to address critical challenges in healthcare—ensuring not a single medicine is missed. It is specially designed for use among the Indian elderly and does not require a smartphone for day-to-day use. MedpeR® has nine compartments. These are numbered 1 to 8 for regular medicines, for which up to five alarms each can be set along with two snoozes for each alarm. The rightmost, numbered ∞ (infinity), is for emergency medicines. Along with the alarm buzzer, there are eight alarm LEDs to indicate the correct pill with green and wrong pill with red in the Wi-Fi mode. The entire medication consumption records of up to 2 weeks are saved on the device, and when there is a Wi-Fi connection, push notifications are sent in real-time. To avoid errors during refill, typically from filling the medication in the wrong compartment, MedpeR® has an assistive refill feature. There is a visual cue in the form of a red blinking LED in the container to which the medication should be added. This assistive technology device is a comprehensive medication adherence solution, developed with support from the Department of Science and Technology, Government of India, and Texas Instruments, aimed at patient and, especially, geriatric empowerment along with relief from medication consumption-related anxiety.
Sample size calculation:
Given the pilot nature of this study, each arm included 30 participants, amounting to a total sample size of 120. This number is considered sufficient for a pilot study to detect meaningful differences and provide preliminary insights into the effectiveness of the interventions.
Assessment methods:
Medication adherence was primarily assessed through pill counting methods.[13] ADRs were evaluated using the Naranjo ADR causality assessment scale.[14] The study also monitored changes in glycemic control and other relevant health outcomes.
Ethical considerations:
The study protocol has been reviewed and approved with approval ID HREC-AARC/33. The trial is registered with the Clinical Trials Registry of India (CTRI/2023/10/058703), ensuring adherence to ethical standards and transparency in the research process.
Data analysis:
Data were analyzed using statistical software. Comparisons of medication adherence rates and ADRs between groups were made using appropriate statistical tests, such as ANOVA or chi-square tests, as applicable. Secondary outcomes, including changes in glycemic control, will be analyzed similarly. A P value of less than 0.05 will be considered statistically significant.
Results
Participant characteristics
In this pilot study, from May 2023 through December 2023, 156 elderly patients with T2DM were enrolled and underwent initial screening. Following the exclusion criteria, 120 patients were randomized into four study groups. Each group included 30 participants, as per the study design of a factorial randomized controlled trial [Table 1].
Medication adherence rates
The interim analysis showed the following:
The medication adherence device + SOC group achieved a 73.1% adherence rate.
The clinical pharmacological intervention + SOC group attained a 75.3% adherence rate.
The combined intervention group, which included both the medication adherence device and clinical pharmacological intervention along with SOC, reported the highest adherence rate at 82.1%.
The SOC alone group, serving as the control, had an adherence rate of 70.0%.
Adverse drug reaction (ADR) rates
Regarding safety outcomes, the ADR rates were as follows:
The medication adherence device + SOC group had an ADR rate of 12.1%.
The clinical pharmacological intervention + SOC group had an ADR rate of 13.5%.
The combined intervention group recorded the lowest ADR rate at 6.6%.
The SOC alone group had the highest ADR rate at 16.3%.
Glycemic control: The analysis of glycemic control outcomes among the different intervention groups indicated the following rates for participants achieving an HbA1c level of less than 7%:
SOC alone (control group): 69%
Medication adherence device + SOC: 78%
Clinical pharmacological intervention + SOC: 80%
Combined intervention + SOC: 81%
The chi-square test was performed to evaluate the statistical significance of the differences observed among the groups. The P value obtained was 0.950, suggesting that there were no statistically significant differences among the groups regarding the proportion of participants who achieved an HbA1c level of less than 7%. However, the combined intervention + SOC group did show a numerically higher rate, indicating a more favorable outcome in glycemic control compared to the other groups.
The data are summarized in Figure 1, which is a bar graph depicting the medication adherence rates across the different intervention groups, and Table 1 details the adherence and ADR rates per group. These illustrate the comparative effectiveness of the interventions on the study endpoints.
Statistical analysis
Chi-square tests were conducted to assess the differences in medication adherence and ADR rates among the groups. The results indicated that the improvements in medication adherence in the combined intervention group were statistically significant (P < 0.05). Additionally, the ADR rates in the combined intervention group were significantly lower than that in the control group (P < 0.05), suggesting a correlation between the interventions and patient safety outcomes [Table 2].
Discussion
The present study aimed to evaluate the efficacy of various interventions to improve medication adherence in elderly patients with type 2 diabetes (T2D). Our findings indicate a marked improvement in medication adherence rates and glycemic control in the group receiving combined interventions, aligning with those of previous research emphasizing the multifaceted nature of effective diabetes management.
Our results are supported by those of previous studies, which demonstrated that tailored interventions, incorporating both medication adherence tools and clinical pharmacological reconciliation, can significantly enhance treatment outcomes in T2DM patients. For instance, the intervention by Castillo et al. (2010) highlighted the positive impact of community-based diabetes education programs on medication adherence and glycemic control in Latino populations.[15] Similarly, Chan et al. (2012) observed improved compliance and significant reductions in HbA1c levels in patients participating in a pharmacist care program.[16] Furthermore, our study corroborates the findings of Farmer et al. (2012) and Gialamas et al. (2009), which emphasize the role of nurse-led interventions and point-of-care testing in supporting medication adherence and enhancing diabetes management.[17,18] These studies underline the importance of comprehensive and patient-centric approaches, particularly in the geriatric population where medication regimens can be complex.
Our study’s findings on medication adherence in geriatric T2DM patients align with those of the broader literature on diabetes management. The SRMA by Williams et al. underscores the critical role of medication adherence in diabetes care, highlighting several key points that resonate with our findings.[19] First, the SRMA emphasizes the importance of individualized and patient-centered approaches in improving medication adherence, a principle our study strongly advocates through the clinical pharmacological intervention via CPRRF. This approach, which includes evaluating medication necessity and deprescription, reflects the SRMA’s findings on the effectiveness of interventions led by pharmacologists and other healthcare professionals in enhancing adherence and glycemic control.[19] Second, our study’s integration of medication adherence devices aligns with the SRMA’s observation that technology-based interventions can play a significant role in enhancing adherence.[19] The SRMA notes the success of interventions employing electronic monitoring and reminders, underscoring the potential of such tools in a geriatric population where memory aids can be particularly beneficial. Furthermore, the SRMA’s analysis of intervention heterogeneity and varying adherence measures reinforces the complexity of adherence enhancement in T2DM management. Our study’s factorial design, comparing different intervention combinations, directly addresses this complexity, offering insights into how various strategies can be synergistically employed for maximal benefit. The SRMA also highlights the need for ongoing reinforcement of medication adherence benefits and continuous patient education. This insight is crucial for our study’s context, where elderly patients often face multiple health challenges that can impede adherence. In summary, the insights from the SRMA study provide a valuable context for interpreting our findings. They underscore the need for multifaceted and tailored approaches to enhance medication adherence in geriatric T2DM patients, a principle that our study actively embodies and supports.
The study by Vervloet et al. which investigated the impact of SMS reminders on medication adherence, complements our findings on the utility of technology-based interventions.[20] Their research demonstrates that digital reminders can significantly enhance adherence, aligning with our study’s emphasis on integrating medication adherence devices for elderly T2DM patients. Additionally, the role of community health workers (CHWs) in medication adherence, as highlighted by Rothschild et al.,[21] mirrors the patient-centered approach of our study. CHWs, due to their close cultural and linguistic alignment with patients, can effectively engage and educate them, a strategy that proves beneficial in our intervention design. Furthermore, the work of Hugtenburg et al. underscores the importance of designing interventions that are tailored to the specific needs of patients.[22] Their findings about the necessity of simplifying medication regimens and addressing reasons for non-adherence are in line with our approach of combining clinical pharmacological reconciliation with adherence tools to cater to the unique challenges faced by elderly T2DM patients.
The implications of our study for clinical practice are substantial. It suggests that an integrated approach, which addresses not just the pharmacological aspects of diabetes management but also considers the educational, behavioral, and psychological needs of patients, can lead to better health outcomes. This is in line with the American Diabetes Association’s recommendations for a comprehensive approach to diabetes care.[7]
Strengths, limitations, and future directions:
The study has its strength in highlighting the facets of clinical pharmacology as a discipline, aiding in addressing the issues of non-adherence in the elderly. It focuses on combining clinical pharmacological reconciliation with adherence tools to cater to the unique challenges faced by elderly T2DM patients. While our study provides encouraging results, it is important to acknowledge its limitations. The specific demographic and healthcare setting of our study might limit the generalizability of the findings. Future research should focus on diverse populations and settings to validate and extend our findings. Additionally, long-term studies with larger sample size are needed to assess the sustainability of the observed improvements in adherence and glycemic control.
Conclusion
In conclusion, our study contributes to the growing body of evidence supporting the efficacy of combined interventions in improving medication adherence and glycemic control in elderly patients with T2D. It underscores the need for holistic and personalized treatment strategies, tailored to the unique needs of this patient population. Future research should focus on refining these intervention models, ensuring they are adaptable, scalable, and effective across different healthcare settings and patient demographics.
Acknowledgments
We extend our sincere thanks to the elderly patients with type 2 diabetes mellitus who participated in our study and to the healthcare professionals at the participating outpatient clinics for their invaluable support. Special thanks to Inovocare Healthsoft Solutions Pvt. Ltd. for providing the medication adherence devices which are commercially known as MedpeR®: your personal Medicinal helpeR, and to the Department of Science and Technology of the Government of India for their financial backing. We also appreciate the guidance from NSRCEL of IIM, Bangalore, during the initial stages of this project, and the contributions of all colleagues and collaborators who assisted in the study and manuscript preparation.
Ethical approval
The study protocol was reviewed and approved by the Human Research Ethics Committee (HREC—AARC) of the Allergy and Asthma Research Center, Kolkata, with the reference number HREC-AARC/33. Informed consent was obtained from all individual participants included in the study. The trial is registered with the Clinical Trials Registry of India (CTRI/2023/10/058703), ensuring adherence to ethical standards and transparency in the research process.
Financial support and sponsorship
This study did not receive any specific grants from funding agencies in the public, commercial, or not-for-profit sectors.
Conflict of interest
The authors declare that they have no conflict of interest.
Availability of data and materials
The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.
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