Jamia Salafiya Pharmacy College. Pulikkal, Malappuram, Kerala, India
Diabetes mellitus is a chronic metabolic disorder with a rapidly increasing global prevalence, leading to severe microvascular and macrovascular complications. The management of diabetes often involves long-term use of various antidiabetic medications, including metformin, sulfonylureas, thiazolidinediones, DPP-4 inhibitors, SGLT2 inhibitors, and insulin. While these agents are essential for glycemic control, they are associated with a wide spectrum of adverse drug reactions (ADRs) ranging from mild gastrointestinal disturbances to life-threatening events such as hypoglycemia, lactic acidosis, and cardiovascular complications. This review critically evaluates the ADR profiles of commonly used antidiabetic drugs, highlighting their pharmacological mechanisms, risk factors contributing to ADRs (such as age, polypharmacy, renal/hepatic impairment, and genetic variability), and the significance of vigilant ADR monitoring. It further explores the role of pharmacovigilance and patient education in minimizing ADR risks and improving therapeutic outcomes. Special focus is placed on Knowledge, Attitude, and Practice (KAP) surveys to assess patient understanding and behaviour regarding ADRs in diabetes management. Studies indicate that enhanced patient knowledge and positive attitudes significantly improve medication adherence and ADR reporting. However, gaps in awareness and misconceptions remain widespread, particularly in resource-limited settings. This review underscores the importance of strengthening educational interventions, implementing effective pharmacovigilance systems, and promoting rational prescribing to optimize drug safety in diabetes care. Addressing these multifaceted issues is crucial to reducing ADR incidence and improving overall disease management and patient safety.
Diabetes mellitus is a chronic, metabolic disease characterized by elevated levels of blood glucose. Over time, this can gradually harm the heart, blood vessels, eyes, kidneys, and nerves. The most common form is type 2 diabetes (T2D), which typically affects adults. It happens when the pancreas makes less insulin, or the body's tissues do not respond well to insulin (insulin resistance). This leads to high blood sugar levels. (1)
Commonly utilized oral antidiabetic drugs (OADs) include metformin, sulfonylureas, thiazolidinediones, DPP-4 inhibitors, and SGLT2 inhibitors. Although these agents are generally effective, their use is associated with certain risks. Adverse drug reactions (ADRs) from these drugs can make people stop taking them, increase healthcare costs and cause health problems or even death. The monitoring and evaluation of ADRs are critical components of pharmacovigilance, as they enhance drug safety and support rational prescribing practices. The type and frequency of ADRs may vary depending on genetic, environmental, nutritional, and socioeconomic factors unique to different populations. (2)
KAP survey is common in research study. KAP is a framework for understanding individuals about health issues, their perceptions and actual behaviours. when people know more about disease like diabetes, it is helpful for changing their attitude and improve behaviour. Many studies have used KAP surveys to check what people know, think, and do about health problems like diabetes, high blood pressure, and others. (3)
Understanding KAP related to ADR in diabetes management is essential to identify gaps in awareness, misconception and risky behaviour among patient.
This review aims to critically analyse current evidence on the KAP levels concerning ADRs in diabetes care and to highlight the need for educational and policy interventions that foster better reporting and management practices. (4) Diabetes mellitus
Diabetes manifests as profound hyperglycemia stemming from defective insulin secretion or action and sometimes both concurrently over time. (5) it is mainly three type, Type 1 Diabetes(T1DM), Type 2 Diabetes (T2DM), Gestational Diabetes mellitus (GDM). (6) Diabetes can cause serious complication, that is categorised as either microvascular or macrovascular. Microvascular problem including nephropathy, neuropathy, retinopathy, which affect the kidney, nervous system, and eye. Examples of Macrovascular problems are peripheral vascular disease, cardiovascular and cerebrovascular stroke. (5)
The incidence of diabetes is rapidly growing worldwide, and it has become a major public health problem. According to the International Diabetes Federation (IDF), over 80% of people with diabetes live in low- and middle-income countries. In 2019, about 463 million people had diabetes, and this number is expected to increase to 578 million by 2030 and 700 million by 2045. (7) Research shows that South Asians are at higher risk of developing diabetes and its complications. This is due to factors like low awareness, poor self-care habits, cultural myths, and rapid urban growth (8). Type 2 diabetes usually affects people between the ages of 50 and 70 and affects both men and women equally. Type 1 diabetes often appears between ages 10 and 12, slightly more in males. However, older adults can also develop Type 1, and children can get Type 2 diabetes (7). Insulin is an important medication for controlling blood sugar. It is the main treatment for Type 1 diabetes and is also used in Type 2 diabetes when oral medicines are not enough. The goal of treatment is to keep blood sugar levels within a normal range (9). Insulin comes in different types rapid, short, intermediate, and long-acting—and is usually injected. Insulin injection occurs most frequently in abdomen.
Antidiabetic Medications Overview
Antidiabetic therapy includes insulin, biguanides, sulfonylureas, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, Sodium-Glucose Cotransporter-2 inhibitors, and Glucagon-like peptide-1 receptor agonists. (10) Each class varies in mechanism of action, efficacy, and side-effect profiles, necessitating individualized treatment plans. (11) Metformin, a first-line agent, is generally well-tolerated but may cause lactic acidosis in rare cases. (12) Sulfonylureas are quite effective, but they often cause hypoglycemia and considerable weight gain in many patients over time. (13) Newer agents like SGLT2 inhibitors and GLP-1 RAs show cardiovascular benefits but carry infection and GI risk. (14)
Drug Classification and ADRs
Oral hypoglycemics drug are used to treat type 2 diabetes mellitus, along with oral hypoglycaemic drug, diet and exercise is important for glycaemic control (15). Initiation treatment without delaying help to prevent risk associated with diabetes such as retinopathy and nephropathy. The main types of medications for managing type 2 diabetes include biguanides, sulfonylureas, meglitinides, thiazolidinediones (TZDs), DPP 4 inhibitors, SGLT2 inhibitors, and alpha glucosidase inhibitors. these are the major class of oral hypoglycaemic agents. (16)
BIGUANIDES
Biguanides—primarily metformin—are typically the first-choice oral medication for managing type?2 diabetes. In this metformin are first line oral antidiabetic drug (16). when compared to phenformin, metformin has less risk of lactic acidosis (17). Biguanide do not enhance the insulin secretion, so it is known as antihyperglycemic agents and it act by increasing sensitivity towards insulin, reduce absorption of glucose and decrease gluconeogenesis (17). Metformin promotes insulin sensitivity by increasing number of insulin receptors and enhance activity of tyrosine kinase. New study shows that the metformin also reduces the fat level in the blood by through a pathway called peroxisome proliferator-activated receptor (PPAR)-α. Metformin is generally very safe, but it can cause stomach problems like diarrhoea, nausea, or indigestion in about 30% of people when they first start taking it. Starting with a low dose usually helps people get used to it. Also, the extended-release formulation of metformin rarely causes stomach issues. A very rare but serious side effect is lactic acidosis, which can happen mostly in people with severe kidney problems. Another thing to know is that metformin works best when the body still makes enough insulin. As diabetes gets worse and the insulin-producing cells fail (like in type 1 diabetes), metformin becomes less effective. Metformin can also lower levels of vitamin B12 and folic acid over time, so these should be checked regularly, especially in older people (16). The most frequent side effects of metformin are issues with the digestive system, such as feeling sick, vomiting, diarrhoea, and stomach pain. (16)
DPP-4
DPP-4 inhibitors, also called “gliptins,” include medicines like sitagliptin, saxagliptin, vildagliptin, linagliptin, and alogliptin. These can be taken alone or together with other diabetes medicines like metformin, sulfonylureas, or TZDs. They work in a similar way to other diabetes pills and usually don’t cause low blood sugar (hypoglycaemia) on their own (16). DPP-4 inhibitors act by blocking the enzyme DPP-4, which normally breaks down these helpful hormones (GLP-1 and GIP). By stopping this breakdown, DPP-4 inhibitors keep GLP-1 and GIP active for longer. (18) These medicines can also help lower blood fat levels after eating. For example, vildagliptin taken for 4 weeks can reduce fats in the blood after a fatty meal in people with type 2 diabetes who haven’t used these drugs before. In people with diabetes and heart disease, sitagliptin has been shown to help heart function and blood flow in the heart’s arteries. The most common side effects seen in studies are nasopharyngitis, upper respiratory tract infection, or headache. In rare cases, some people taking sitagliptin (alone or with metformin) have developed pancreatitis (inflammation of the pancreas). If gliptins are combined with sulfonylureas, the risk of low blood sugar may increase. For older people, DPP-4 inhibitors help lower blood sugar but don’t really reduce appetite, so they don’t cause much weight or muscle loss. These drugs are usually safe for people with moderate to severe kidney problems if the dose is adjusted properly (22)
GLP-1 Receptor Agonists
GLP-1 receptor agonists are Exenatide and liraglutide. These drugs act like the body’s own GLP-1 hormone but are designed to resist being broken down by the DPP-4 enzyme, so they stay active longer. They’re especially helpful for younger people who have recently been diagnosed with type 2 diabetes and who have extra weight and poor metabolic control. These drugs can help with weight loss and improve blood sugar levels. However, they shouldn’t be used by people with kidney failure. (16) Exenatide is a medicine similar to a natural hormone called exendin-4 and is about 53% similar to human GLP-1. It’s approved for use on its own or with other diabetes medicines like metformin or sulfonylureas. Because exenatide doesn’t last very long in the body (about 2.4 hours), it’s usually given twice a day. Studies show that adding exenatide (10 µg) to metformin helps people lose about 2.8 kg more than using metformin alone. Most people tolerate exenatide well, though some may have mild to moderate stomach side effects, like nausea.
Liraglutide is another GLP-1-like medicine, and it’s even closer to the body’s natural GLP-1 (97% identical). It works for about 24 hours, so it’s given once daily. When used alone or with other diabetes pills, liraglutide can lower HbA1c by about 1.5%. It also helps with weight loss for example, people using liraglutide with metformin and a sulfonylurea lost around 3.2 kg more than with pills alone. Liraglutide can also slightly lower blood pressure (by about 2–7 mmHg). It’s generally safe but can cause nausea, and the risk of low blood sugar goes up if it’s used together with sulfonylureas. (16)
SGLT2 Inhibitors
SGLT2 inhibitors such as canagliflozin, dapagliflozin, and empagliflozin are a newer type of diabetes medicine. They lower blood sugar by making the kidneys pass more glucose into the urine instead of reabsorbing it. This happens because they block a protein called SGLT2 in the kidneys that normally pulls sugar back into the blood. Because they don’t rely on insulin to work, SGLT2 inhibitors can help people with type 2 diabetes even in later stages, when the pancreas no longer makes enough insulin. These drugs can also help with some weight loss and slightly lower blood pressure. However, they do have some risks. People taking SGLT2 inhibitors can get more urinary tract infections (which can sometimes get serious and lead to kidney infections) and genital yeast infections. In rare cases, these medicines can cause ketoacidosis, a serious condition where the body makes too many ketones. Patients should stop taking the drug and get medical help right away if they feel very nauseous, start vomiting, feel unusually tired, or have stomach pain these can be warning signs of ketoacidosis. (16)
Meglitinides
Meglitinides like repaglinide and nateglinide are diabetes medicines that help the pancreas release more insulin. They work in a similar way to sulfonylureas by attaching to the same receptor on the beta cells in the pancreas. However, meglitinides don’t bind as strongly as sulfonylureas do, so they work for a shorter time. This makes them short-acting insulin secretagogues, which gives people more flexibility in when they take them. One key point is that meglitinides need higher blood sugar levels to trigger insulin release compared to sulfonylureas. This means they’re slightly less powerful than sulfonylureas but can be safer in certain situations. Doctors may choose meglitinides for people who don’t eat meals at regular times or for patients who get low blood sugar later after eating when using sulfonylureas. Because they act quickly and wear off faster, they can help match insulin release to unpredictable meal times. (16)
Thiazolidinediones (TZDs)
Like metformin (a biguanide), TZDs help the body use insulin better. The main TZDs are rosiglitazone and pioglitazone. They work by activating a protein called PPAR, which helps the body take up more glucose in fat tissue, muscles, and the liver. TZDs lower insulin resistance in several ways: They reduce the build-up of harmful free fatty acids. They lower inflammation in the body, they increase levels of adiponectin, a hormone that helps the body respond to insulin they help keep the pancreas’s insulin-producing cells healthy and working longer.
All these actions make insulin work better and slow down the burnout of beta cells. However, TZDs come with significant risks. One major problem is that combining TZDs with insulin can cause heart failure. Because of these safety concerns, doctors usually don’t use TZDs as a first choice or even as a preferred add-on treatment anymore. (16) Individuals with diabetes have a higher risk of developing cardiovascular disease and Oedema may develop as a result of thiazolidinedione treatment. It could be an early manifestation of congestive heart failure. rosiglitazone causes weight gain even when used on its own and used in combination with metformin. (23) Long-term use of thiazolidinediones (TZDs) may increase the risk of bone fractures, especially in postmenopausal women. Some studies suggest that pioglitazone could increase the risk of bladder cancer, though the results are not clear. (24)
Sulfonylureas
Sulfonylureas are diabetes medicines that lower blood sugar by making the pancreas release more insulin. They do this by blocking certain channels ATP-sensitive potassium (KATP) channel (16) found in found in the heart, skeletal muscles, and smooth muscles. (19) (KATP channels) in the beta cells. They also help a bit by slowing down sugar production in the liver and by stopping the breakdown of fat into fatty acids. They also help keep more insulin in the body by slowing how fast the liver clears it out. Today, sulfonylureas are mostly used as a second-line or add-on treatment for type 2 diabetes. There are two groups of sulfonylureas:
First-generation ones: like chlorpropamide, tolazamide, and tolbutamide. These are older, work slower, last longer, and carry a higher risk of causing low blood sugar.
Second-generation ones: like glipizide, glimepiride, and glyburide. These newer ones work better at lower doses, need to be taken less often, and are generally safer. Among them, glimepiride is known to be the safest option. Low blood sugar (hypoglycemia) is the most important side effect of sulfonylureas. Other mild side effects can include headache, dizziness, nausea, allergic reactions, and weight gain. These drugs are not safe for people with serious liver or kidney problems, or for pregnant women, because they can cause long-lasting low blood sugar in newborns. Some other medicines like aspirin, allopurinol, sulfa drugs, and fibrates can make sulfonylureas stronger and raise the risk of low blood sugar, so they need to be used carefully together. Combining sulfonylureas with other diabetes pills or insulin can also increase this risk. Finally, people who take beta-blockers for blood pressure may not feel the warning signs of low blood sugar, so doctors need to be extra cautious when combining these medicines. (16) Chlorpropamide and glibenclamide exhibit a higher incidence of hypoglycemic events compared to other sulfonylureas. Weight gain is most common side effect. It increases the risk of cardiovascular diseases. (21)
Insulin
If your blood sugar keeps rising quickly and you already take more than one diabetes pill, you might need to start insulin sooner. If your HbA1c is above 7.5%, it’s time to think about insulin. If it’s above 8%, another pill probably won’t help much unless you can improve your diet and exercise. sugar levels are going up fast, pills alone may not work, so insulin can help bring your sugar back under control. Benefits of starting insulin early is that it makes diabetes care simpler. avoids the burden of trying more pills, checking if they work, and switching when they stop working (20)
Table 1: Antidiabetic Medication and their ADRs (15)
|
CLASS OF DRUG |
EXAMPLE |
MECHANISM OF ACTION |
ADVERSE DRUG REACTION |
|
Biguanide |
Metformin |
Insulin sensitizer Numerous effects on inhibition of hepatic glucose production |
Mild weight loss due to anorectic effect Lactic acidosis (very rare) May cause nausea/vomiting or diarrhea after introduction, which may result in electrolyte or pH alterations. Vitamin B12 deficiency, which may cause anemia and neuropathy |
|
Dipeptidyl peptidase-4 inhibitor |
Sitagliptin Saxagliptin Vidagliptin Linagliptin Alogliptin |
Inhibition of degradation of GLP |
Pancreatitis Saxagliptin Upper RTI infection. CHF by degradation of BNP |
|
Sodium-glucose cotransporter inhibitor |
Canagliflozin Dapagliflozin Empagliflozin |
Glucosuria due to blocking (90%) of glucose reabsorption in renal PCT; insulin independent mechanism of action |
Ketoacidosis (rare) Genital mycosis May increase LDLc Bone fractures |
|
Insulin |
Short-acting Regular Humulin R Novolin R Intermediate Acting NPH Long-acting Insulin glargine Insulin detemir Rapid-acting Lispro Aspart Glulisine |
Activation of insulin receptors and downstream signaling in multiple sensitive tissues |
Lipoatrophy and lipohypertrophy at sites of injection Allergy to injection components |
|
GLP-1 agonists |
Liraglutide Exenatide Dulaglutide |
Activate GLP1 receptor Increased insulin secretion, decreased glucagon, delayed gastric emptying, increased satiety |
Nausea, vomiting, pancreatitis, C cell tumor of thyroid |
|
Sulfonylureas |
Glimepiride Glipizide Glyburide |
Insulin secretion |
Increased cardiovascular disease risk, mainly due to hypoglycemia Weight gain |
|
Thiazolidinediones |
Rosiglitazone Pioglitazone |
Insulin sensitizer |
Weight gain, Cardiac failure, pedal edema, Bladder cancer, fractures |
Risk Factors for ADRs in Diabetic Patients
1. Age
Older adults are at increased risk of ADRs due to physiological changes affecting drug pharmacokinetics and pharmacodynamics, such as reduced renal clearance and altered liver metabolism. In diabetic patients, this vulnerability can amplify the effects of medications like sulfonylureas and insulin, increasing the incidence of hypoglycemia and other ADRs (21).
2. Polypharmacy
Polypharmacy frequently occurs in diabetes treatment particularly among patients suffering from numerous chronic conditions and other serious health issues. The concurrent use of antidiabetics, antihypertensives, and lipid-lowering agents increases the probability of drug-drug interactions and ADRs. A study observed that the majority of reported ADRs in diabetic patients occurred in those prescribed five or more drugs (21).
3. Comorbidities
Diabetic patients often suffer from cardiovascular disease, nephropathy, and hepatic disorders, which interfere with drug metabolism and excretion. These comorbidities compound the risk of ADRs. In one clinical evaluation, patients with hypertension and other comorbidities were found to be at significantly greater risk of developing suspected ADRs (22).
4. Renal and Hepatic Impairment
Renal and hepatic impairments significantly alter the pharmacokinetics of antidiabetic drugs. For instance, the buildup of metformin in cases of renal impairment can lead to lactic acidosis. Research confirms impaired kidney function strongly correlates with adverse drug reaction incidence in people with diabetes mellitus type 2 typically.
5. Hypoglycemia Risk
Hypoglycemia occurs frequently as major adverse drug reaction strongly linked with insulin and sulfonylureas. It poses serious health threats especially for elderly folks and individuals with irregular eating habits. In observational studies, hypoglycemia was among the most frequently reported ADRs, particularly in patients on insulin or glibenclamide therapy (21).
6. Genetic Factors
Although not the primary focus of the provided original articles, some observational evidence suggests that individual variability, possibly influenced by genetic differences, may affect drug responses. However, more research is needed to establish strong clinical associations.
7. Socioeconomic and Behavioural Factors
Patient non-adherence due to poor health literacy, economic constraints, or cultural practices can lead to misuse of medications and increase the risk of ADRs. In real-world settings, inappropriate self-medication and underreporting were commonly noted in patients with low socioeconomic status (22).
Recognizing and understanding of the various risk factors is essential for effective diabetes prevention and management. Addressing modifiable risks through lifestyle changes allows public health initiatives to significantly lower diabetes incidence. Core strategies include encouraging balanced diets, consistent physical activity, maintaining a healthy weight, and quitting smoking.
Diabetes is a multifaceted condition driven by an interplay of genetic, demographic, and lifestyle elements. Gaining insight into these contributing factors empowers healthcare providers, policymakers, and individuals to take preventive actions and promote early detection (23).
Adverse drug reactions (ADRs)
Adverse drug reactions (ADRs) are very common, and it is usually an unrecognized and not reported frequently. (25) World Health Organization (WHO), defines an ADR is “A response to a drug which is noxious and unintended, and which occurs at doses normally used for prophylaxis, diagnosis, or therapy of disease or the medication of physiologic function.” Whereas an adverse drug reaction, is defined as: Any unwanted reaction that occurs during the treatment with a pharmaceutical product that is noxious and unintended. (26) There are many adverse drug reactions (ADRs) by antidiabetic drugs. The first line treatment for the Diabetes management is oral hypoglycemic agents. It is widely prescribed for the treatment of Type 2 Diabetes, either alone or in combination with insulin therapy.
ADR Monitoring and Detection
Adverse Drug Reaction (ADR) monitoring refers to the systematic and ongoing observation of any harmful or unwanted effects associated with drug use. The discipline of pharmacovigilance plays a crucial role in the detection and assessment of these reactions.
It is essential for regulatory authorities to evaluate the safety of pharmaceuticals available in the market by identifying and recording any suspected adverse responses. ADRs can be triggered by a range of products including conventional drugs, herbal preparations, medical devices, biological agents, and even cosmetics. The core objective of implementing such monitoring practices is to ensure that only safe and therapeutically effective medicines are administered to patients.
Failure to report adverse incidents may result in severe or hazardous consequences for public health. Therefore, robust and well-structured ADR surveillance programs are vital in minimizing the negative impact of medical therapies.
Benefits of Adverse Drug Reaction (ADR) Monitoring
Implementing an ADR monitoring and reporting system provides several important advantages:
Types of Studies and Methods in ADR Detection
ADR monitoring incorporates multiple research approaches to detect, document, and evaluate adverse drug events. The key methods include:
1. Case Reports: This approach is useful for reporting unexpected or rare adverse reactions also known as Type-B ADRs. These reports often emerge during routine clinical observations.
2. Anecdotal Reporting: These are individual observations made by healthcare professionals when a patient experiences a specific adverse effect. Though informal, they can sometimes prompt more rigorous follow up studies.
3. Spontaneous (Voluntary) Reporting Systems: This is one of the most widely adopted and effective strategies in pharmacovigilance. Healthcare professionals submit reports without external prompting, which allows for the detection of both common and serious ADRs.
4. Intensive Monitoring Studies: Patients are systematically monitored over time to record any adverse events occurring after drug administration. These studies typically focus on defined patient groups. The limitations include small sample sizes and short observation periods, although statistical tools can enhance their reliability.
5. Contingent Studies: These studies involve tracking individuals receiving similar medications and recording their responses. However, they are costly, include a small sample, and often lack a control group, making them difficult to execute, especially for newly introduced drugs.
6. Case Control Studies (Retrospective): This design investigates whether patients who developed a particular adverse event had previously taken a specific medication. Their data is compared with that of a control group without the adverse event but similar in other characteristics. It’s useful for assessing causality, although it cannot detect new ADRs.
7. Case- Cohort Studies: This hybrid approach combines the elements of both prospective cohort and retrospective case control studies, allowing for broader evaluation and more reliable conclusions.
8.Record Linkage Studies: This method involves analysing and linking data from prescription logs, hospital records, and patient files to identify potential connections between drug exposure and illnesses.
9. Meta -Analysis: A statistical technique that synthesizes findings from multiple independent studies to determine the overall risk or effect size. It also explores the reasons for variation among study outcomes.
10. Use of Population Statistics: In cases where suspected ADRs are common, researchers may initiate case-control or experimental cohort studies to examine the issue more systematically.
The emergence of multiple drug-related incidents has highlighted the necessity for strict laws and regulatory measures to ensure the safe use of medicines. One such example is the withdrawal of rofecoxib from the European market, which led to significant criticism of the FDA’s post-marketing surveillance protocols. In response, a more robust pharmacovigilance framework was developed to enhance the detection and reporting of known drug-related risks.
Role of pharmacovigilance in monitoring ADRs
During the early post-marketing phase, medications may be used by patient populations that differ significantly from those enrolled in clinical trials. Moreover, once a drug enters the market, it may be administered to a much larger and more diverse population in a relatively short time frame. This widespread exposure can lead to the identification of new information related to both the benefits and potential risks of the drug. Thus, pharmacovigilance plays a key role in generating comprehensive data about the safety profile of approved medications to promote their safe and effective use.
Well-designed pharmacovigilance plans are crucial in reducing the incidence and severity of adverse drug events. Although clinical trials are the primary method for gathering safety data before a drug reaches the market, these trials have limitations. Typically, they involve a limited number of participants, and the study population may not accurately represent the broader patient groups who will use the drug post-approval. As a result, it becomes difficult to fully understand a drug’s mechanism of action or its adverse effects in real-world use.
To enhance the detection and prevention of suspected ADRs, various methods are employed as part of pharmacovigilance efforts, especially during and after the post-marketing phase.
Preventive measurement and Management of ADR
Preventive strategies such as balanced nutrition, regular physical activity, weight management and mental health support are essential components of effective diabetes care. While a wide range of treatment options now exists, emphasizing lifestyle-based prevention remains crucial for improving outcomes and reducing the risk of complications. Regular self-monitoring of blood glucose can aid in effective diabetes self-management and assist in adjusting medications, particularly for individuals using insulin. Various factors contribute to non-adherence and discontinuation of treatment, such as patients feeling the medicine isn’t effective, fear of low blood sugar, difficulty getting the medicine, and the occurrence of adverse drug reactions. (27) Monitoring ADRs in patients taking oral anti-diabetic drugs is very important because these medications are usually taken for a long time. Preventable adverse drug reactions (ADRs) can be minimized through better and more accurate prescribing practices. Educating healthcare professionals about ADRs and encouraging proper reporting can enhance reporting rates. Effective planning and continuous monitoring of drug therapy are essential to prevent the occurrence of ADRs. (28)
KAP on Diabetes care
Knowledge and attitude play crucial roles in managing adverse drug reactions (ADRs) in diabetes care. Higher knowledge about diabetes and its treatments is directly linked to better self-management behaviours, including correct medication use and early recognition of ADRs, which can reduce the risk of complications such as hypoglycemia and injection site reactions. (29) (31) Positive attitudes toward diabetes and its management further enhance these behaviours, as patients with a constructive outlook are more likely to adhere to treatment plans and report ADRs when they occur. (30) Attitude also mediates the relationship between knowledge and practice, meaning that even with good knowledge, a negative attitude can hinder effective self-care and ADR management. (31) Patient education, especially when delivered by healthcare professionals or patient organizations, significantly improves both knowledge and attitudes, leading to greater risk awareness and a higher likelihood of reporting ADRs. However, gaps remain: some patients may have a positive attitude but lack the necessary knowledge to translate this into safe practices, while others may have knowledge but lack motivation or support to act on it. Socioeconomic factors, education level, and access to counselling also influence how knowledge and attitude affect ADR management (32)(33) Overall, strengthening both knowledge and attitude through targeted education and support is essential for effective ADR management in diabetes care. (34)
CONCLUSION
Diabetes mellitus is a complex and growing public health concern, especially in low- and middle-income countries. Although antidiabetic medications play a vital role in glycemic control and complication prevention, they cause ADRs. Adverse drug reactions (ADRs) associated with these medications ranging from mild gastrointestinal symptoms to life-threatening hypoglycemia and lactic acidosis highlight the importance of vigilant monitoring and individualized therapy.
This review underscores the necessity of pharmacovigilance in detecting and managing ADRs, especially in high-risk groups such as elderly patients, those with polypharmacy, renal or hepatic impairment, and coexisting comorbidities. Socioeconomic, behavioural, and genetic factors further influence the incidence and reporting of ADRs, pointing to the need for culturally appropriate interventions and education.
Furthermore, understanding patients' Knowledge, Attitude, and Practice (KAP) regarding ADRs is crucial in closing the gap between medication safety and real-world adherence. Enhancing KAP through targeted education can empower patients to recognize, prevent, and report ADRs, ultimately improving treatment outcomes and quality of life.
To ensure safer diabetes management, a multifaceted strategy is required combining optimized prescribing practices, routine monitoring, patient education, and strong pharmacovigilance systems. Strengthening these components can significantly reduce ADR-related complications and promote rational use of antidiabetic medications.
REFERENCES
Nasheetha Rushad C P, Nidha Fahma SM, Shakira VP, Shifa M, Anjali C S, Dr. Kameswaran R, Dr. Sirajudheen M. K., Diabetes and Its Treatment: A Review of Adverse Drug Reactions and Risk Management, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 8, 67-80. https://doi.org/10.5281/zenodo.16680753
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