Introduction
Diabetes mellitus (DM) is a group of metabolic disorders characterized by chronically high blood glucose levels. It is associated with abnormal fat and protein metabolism, leading to acute complications like diabetic ketoacidosis and hyperosmolar hyperglycemic syndrome, as well as chronic vascular and nerve damage. 1 Diabetes is a growing health concern globally, affecting 537 million adults (10.5%) worldwide in 2021, with projections indicating this will rise to 783 million by 2045. In South-East Asia, including India, the incidence of diabetes has been steadily increasing for over 20 years. Specifically, in India, the diabetes prevalence was 9.6% in 2021 and is expected to rise to 10.9% by 2045, highlighting the urgent need for improved management and access to affordable treatments for this chronic condition. 2
Table 1
SGLT2 inhibitors combination drugs
Table 2
Sulfonylureascombination drugs
Table 3
DPP-4 Inhibitors, Thiazolidinediones, andother combinations
Table 4
SGLT2, DPP-4, Biguanides and others (3 drug combinations)
Table 5
Sulfonylureas, Alpha-Glucosidase inhibitors and others (3 drug combinations)
Table 6
Total number of brands and formulations of oral antidiabetic FDCs
The management of DM typically begins with monotherapy; however, as the disease progresses, polytherapy often becomes necessary to achieve optimal glycemic control. A major challenge in managing chronic conditions like diabetes is patient non-adherence, especially when multiple medications are required. 3 Non-adherence to polytherapy in diabetes management worsens glycemic control, increasing the risk of complications like cardiovascular disease. Simplified treatment regimens, such as Fixed Dose Combinations (FDCs) are crucial to improving adherence and reducing hospitalizations.4 FDCs provide a potential solution by combining two or more drugs into a single pill, which simplifies treatment regimens, reduces the pill burden and can improve both adherence and tolerability. 5 This long-term treatment of diabetes places a significant economic burden on patients, especially in a country like India where a large portion of the population belongs to lower and middle-income groups. For many patients, the cumulative costs of medication, regular monitoring, and doctor visits can be overwhelming.6
In the Indian pharmaceutical market, the wide variation in the prices of oral antidiabetic drugs, especially FDCs, which can significantly affect the patient’s ability to access these medications, regardless of their therapeutic merits.7 This price disparity can lead to treatment discontinuation or switching to less effective alternatives, which can have serious health implications. Addressing these price variations is essential to ensure that all patients, regardless of their financial situation, have access to necessary diabetes medications.8
This study aims to analyse the price variations of FDCs of oral antidiabetic agents in India. By evaluating these cost disparities, the study intends to highlight the percentage price variations in different brands of same formulations of orals antidiabetic FDCs. This is especially important in India, where the affordability of long-term diabetes management plays a crucial role in enhancing patient outcomes and reducing the impact of diabetes-related complications.
Materials and Methods
This is an analytical study, conducted from August to September 2024. The prices of 118 different formulations of 34 oral antidiabetic FDCs were examined. Price data for each drug (per 10 tablets), in the same strength and dosage form produced by various manufacturers, were collected from “Pharma Sahi Daam”, an openly accessible platform provided by the NPPA. 9
Only FDCs were included, while single drug combinations and drugs produced by a single manufacturer were excluded from the analysis. The minimum and maximum costs, total number of brands for each FDCs were analysed. Microsoft Excel Office 2021 was used for the statistical analysis throughout the study.
The cost ratio, which compares the highest to the lowest cost of the FDCs, was calculated by
The percentage cost variation between the maximum and minimum prices of FDCs was calculated by
Results
This study analysed the prices of all oral antidiabetic FDCs and observed significant price variations among different brands of the same formulations. The highest percentage cost variation in SGLT2 inhibitors combinations was founded in dapagliflozin + sitagliptin (5 mg + 50 mg) as 1722.5% followed by dapagliflozin + metformin (10 mg + 500 mg) as 1591.54% and the least percentage cost variation was founded in empagliflozin + metformin (12.5 mg + 500 mg and 12.5 mg + 1000 mg) as 0% (Table 1).
The highest price variation in sulfonylureas combinations was founded in glimepiride + metformin (2 mg + 1000 mg) as 15958.33% followed by glimepiride + metformin (1 mg + 1000 mg) as 9665% and the least price variation was founded in gliclazide + metformin 60 mg + 1000 mg) as 5.88% (Table 2 ). Similarly, the highest price variation in DPP-4 Inhibitors, thiazolidinediones, and other combinations were founded in vildagliptin + metformin (50 mg + 500 mg) as 2207.69% followed by voglibose + metformin (20 mg + 500 mg) as 1349.63% and the least price variation was founded in teneligliptin + metformin (0.2 mg + 1000 mg) as 0.22% (Table 3).
In SGLT2, DPP-4, biguanides and others (3 drug combinations), the highest price variation was founded in sitagliptin + dapagliflozin + metformin (100 mg + 10 mg + 500 mg) as 2553.85% and the least price variation was founded in dapagliflozin + linagliptin + metformin (10 mg + 5 mg + 500 mg) as 0% (Table 4). Similarly, in sulfonylureas, alpha-glucosidase inhibitors and others (3 drug combinations), the highest price variation was found in voglibose + metformin + glimepiride (0.3 mg + 500 mg + 1 mg) as 209900% and the least percentage price variation was founded in voglibose + metformin + gliclazide (0.2 mg + 500 mg + 60 mg) as 4.17% (Table 5).
Following price variations, the highest number of brands available for oral antidiabetic FDCs in the Indian market is for glimepiride + metformin with 447 brands in total followed by voglibose + metformin + glimepiride with 239 brands in total. The least number of brands was founded in pioglitazone + vildagliptin and teneligliptin + dapagliflozin with 2 brands each (Table 6 ).
Discussion
The Indian market for oral antidiabetic FDCs exhibits significant price variability influenced by market dynamics, regulatory factors, and brand positioning. Key factors of pharmaceutical expenditures include the number of prescribed medicines, the introduction of new drugs, and fluctuations in drug prices and utilization patterns. 10 Additionally, demographic trends, such as an aging population and varying socio-economic statuses, impact consumption patterns. Health care reforms and direct-to-consumer advertising may also boost demand for specialized medications, contributing to further variations in drug prices.11 Price variations in essential medications have long been a significant challenge in healthcare, often affecting both the affordability and accessibility of treatments. These disparities can directly impact patient adherence, as higher costs may lead to delayed treatment initiation, inconsistent medication use, or even complete discontinuation, particularly among economically disadvantaged populations. 12
In our analysis, we observed significant variations in the cost of oral antidiabetic FDCs. Existing literature by Jadhav NB et al., 13, Mehani R et al., 14, Thacker et al., 15, Veena et al., 16 and Amaravati et al., 17 spanning from 2012 to 2023, has consistently demonstrated significant variations in the pricing of oral antidiabetic agents, which aligns with our findings. Notably, these studies highlight that price fluctuations and percentage variations are not static but have shown changes annually. Furthermore, the data indicate a clear upward trend in price variations over the years, suggesting a progressive increase in the cost of these medications. This trend underscores the growing economic burden on patients.
Price control mechanisms such as the DPCO in India aim to regulate the prices of essential medicines, including FDCs, by capping the prices of drugs listed under the National List of Essential Medicines (NLEM).18 While this has made some FDCs more affordable and accessible, there are still disparities in price regulation. For example, many drugs outside the NLEM are not subjected to strict price controls, leading to significant price variations.19 Additionally, implementation gaps in the system allow pharmaceutical companies to introduce new FDCs at premium prices by slightly modifying drug compositions to bypass existing regulations. In fact, pharmaceutical companies often exploit regulatory loopholes by launching reformulated or slightly altered FDCs at premium prices, contributing further to the inconsistency in drug pricing. This creates disparities and challenges in controlling drug costs effectively.20
The rationality of FDCs is debated, especially when some combinations may not provide any additional therapeutic benefits over individual drugs. Clinical decision-making can be influenced by price variations, particularly when higher-priced combinations offer no significant advantage. In these cases, prescribers may prefer cheaper alternatives that are equally effective. The lack of clear guidelines regarding the rational use of FDCs further complicates this issue.21 Price disparities may also inadvertently promote irrational prescribing patterns, as healthcare providers might either favour expensive medications due to perceived quality or be limited by patient affordability concerns. When comparing internationally, other nations implement various strategies such as external reference pricing or value-based pricing models, which may offer insights into strengthening India's approach to pharmaceutical cost regulation. 22
Regulatory Recommendations and Future Directions
Establish standardized pricing frameworks to mitigate price variations among oral antidiabetic FDCs, ensuring affordability for all patients.
Refine NPPA guidelines to specifically address extreme price disparities in high-demand oral antidiabetic FDCs formulations, ensuring fair pricing practices.
Implement routine assessments to monitor pricing trends and ensure compliance with regulations, allowing for timely interventions when necessary.
Launch patient education campaigns that not only inform patients of price variations but also promote awareness about the efficacy of more affordable alternatives, which can maintain adherence without sacrificing treatment outcomes.
Provide training and resources for healthcare providers on price variations among oral antidiabetic medications, encouraging cost-effective prescribing options to improve patient adherence and access.
Conclusion
The findings of this study reveal a significant variation in the prices of oral antidiabetic FDCs in the Indian pharmaceutical market. In some cases, the price disparity between different brands of the same formulation is alarmingly high. These substantial differences in cost pose a considerable barrier to patients, particularly in a country like India where affordability is a critical factor in chronic disease management. While FDCs are intended to simplify diabetes management and improve adherence, the wide variation in pricing limits their accessibility, potentially forcing patients to switch to less effective alternatives or abandon treatment altogether. In conclusion, there is an urgent need for pricing control authorities, such as the NPPA, to take immediate and stringent action to address these disparities, ensuring fair and consistent pricing across different brands of oral antidiabetic FDC’s.
