Prescription Errors in the Management of Type 2 Diabetes Mellitus

The treatment of people with type 2 diabetes mellitus (T2DM) has become more and more complex as a result of discovery of an increasing number of drug classes to treat this condition, thereby increasing the probability of prescription errors (PEs). Moreover, over the past two decades, there has been a rapid advancement in the evidence base for the management of people with T2DM that has made it difficult for general physicians to keep abreast of the latest developments, leading to knowledge-based errors in prescription. Drug-related problems (DRPs) are defined as an event or circumstance involving drug therapy that does, or potentially can, interfere with desired health outcomes.[1] It includes medication errors (MEs) (a failure in the treatment process that leads to or has the potential to lead to, harm to the patient),[2] adverse drug reactions (ADRs) (any noxious response to a drug which is unintended, occurring at doses normally used in humans),[3] and adverse events (AEs) (an adverse outcome attributed to an action of a drug).[3] MEs may occur while selecting a particular medication to use and/or while writing a prescription (PEs), manufacturing or dispensing the formulation, administration of the drug, and in monitoring therapy. In this article, we shall limit ourselves to PEs in the management of people with T2DM, which includes either a wrong choice of a medication or an error in the actual writing of the prescription. This article shall neither dwell on errors in manufacturing, dispensing, administering, or monitoring of drug therapy nor touch on ADRs or AEs. Issuing a prescription to a person with T2DM includes a decision-making process as to which drug to choose, in what dose, and for how long (“prescribing”), and the actual “act of writing” of the prescription; errors can happen during either of these two processes. A clinically meaningful prescribing error occurs when there is an unintentional significant reduction in the efficacy of the treatment, or an increase in the risk of harm, as a result of a “prescribing fault” or an error during the actual “writing of the prescription.” MEs, including errors in prescription, can result either because of mistakes (arising out of lack of knowledge or failure to follow the known rules of management) or because of skill-based errors (“slips” due to action-based errors or “lapses” arising out of memory-based errors).[4] PEs can happen both in the inpatient (IP) and outpatient (OP) settings. The basic principles of errors remain the same; the nature, scale, and its impact on health outcomes differ among IP and OP settings. Naseralallah et al. in a systematic review of 24 studies on the prevalence of MEs in unselected patients in the OP and ambulatory settings found that PEs were common (prevalence of 0%–91%); the most common among these were errors in dosing (prevalence of 0%–41%), followed by suboptimal/wrong drug prescriptions, errors in frequency, and errors in duration of use of prescribed medication.[5] Awang Jihadi et al., in a systematic review including 20 studies on DRPs in hospitalized people with T2DM, found that the overall prevalence of DRPs ranged from 7% to 94%; the most common drug classes involved were antidiabetics, antihypertensives, and antiplatelet agents.[6] A complete prescription should include the identity of the recipient, appropriate choice of drug suiting the condition being treated, proper spelling and name of the drug (including generic name), its formulation, route of administration, dose, when and how frequently to take, and for how long. Errors can creep in during any of these multiple steps of writing a prescription. At the very outset, one must avoid issuing a prescription to a wrong patient either as a result of misidentification or due to oversight: a not too uncommon situation in the IP setting when a busy, and often tired, physician mistakenly writes a medication in the drug chart of another patient; on rare occasions, two patients with a similar sounding name might create confusion and lead to an error in prescription. Similar situations must be avoided at all costs in the OP setting as well. Similar situations must be avoided in the OP setting as well. PEs arising as a result of “prescribing fault” include irrational, ineffective, inappropriate, under-, and over-prescribing.[7] Writing two anti-diabetic medications belonging to the same class simultaneously in the prescription of a patient [two sulfonylureas such as glimepiride and gliclazide, two dipeptidyl-peptidase inhibitors (DPP-4i) such as vildagliptin and sitagliptin or two incretins such as a DPP-4i and a glucagon-like peptide 1 receptor agonist (GLP-1RA)] is an example of an “irrational prescription”. Using a single antidiabetic drug class, such as an alpha-glucosidase inhibitor or a DPP-4i (limited efficacy) in a person with T2DM with grossly elevated blood glucose is an example of an “ineffective prescription.” Another such example is the use of a sodium glucose cotransporter 2 inhibitor (SGLT2i) for the control of blood glucose in a person with T2DM with advanced chronic kidney disease (CKD). Many a times, PEs are due to inappropriate prescribing of an antidiabetic drug class. Prescribing an incretin-based therapy in a person with a history of recurrent pancreatitis, a SU for a person at high-risk for hypoglycemia, or a SGLT2i in a person with severe and/or recurrent urinary tract infection are all examples of an “inappropriate prescription.” “Under-prescription” refers to failure to prescribe a drug that is appropriate and indicated and/or prescribing a lower-than-recommended dose of the appropriate drug.[7] Failure to prescribe a particular class of an antidiabetic drug when indicated, and/or hesitation to prescribe the adequate number and appropriate doses of antidiabetic medications for fear of adverse effects are examples of under-prescription. Failure to prescribe a SGLT2i or a GLP-1RA in the absence of a contraindication to a person with T2DM and established atherosclerotic cardiovascular disease or at high risk for CVD is an error of under-prescription.[8] Similarly, the failure to prescribe a SGLT2i in the absence of contraindications in a person with T2DM with heart failure or CKD is an error of under-prescription.[8] A very common example of under-prescription concerns the use of insulin in people with T2DM; among other causes, a reluctance among physicians to initiate insulin therapy, and hesitation to aggressively up-titrate the dose of insulin for fear of precipitating hypoglycemia contributes to the long delay in insulin initiation in deserving people with T2DM. Under-prescription could either be due to a mistake (due to lack of specific knowledge or failure to follow the known rules of management) or a skill-based error (a lapse arising out of memory-based errors).[2] Moreover, many a times, the cost of medications contribute to under-prescription; the use of GLP-1RAs and analog insulins are prime examples of cost being a reason for under-prescription. Opposite to under-prescription, PEs due to “over-prescription” of a drug, wherein an antidiabetic drug class has been prescribed in a higher than recommended dose, frequency or duration, is not uncommon. Failure to reduce the dose of drugs based on prevailing situation can lead to over-prescription. For example, it is recommended that the dose of metformin should be reduced to 1 g once daily when the estimated glomerular filtration rate (eGFR) is ≤45 mL/min; failure to do so leads to over-prescription. Similarly, the dose of a few DPP-4i needs reduction as renal function deteriorates.[8] Polypharmacy, defined as use of five or more drugs, is often a necessity in a person with T2DM because of the need to treat not only blood glucose values but also the associated comorbidities, such as hypertension and hyperlipidemia; however, it is not uncommon to see pointless over-prescription of drugs contributing to polypharmacy such as vitamins, antioxidants, and various health supplements.[9] It is important to recognize PEs and to try and rectify them. This includes improvement both at individual physician level as well as in the systems and processes of the health care facility. At an individual level, the physician must update his or her knowledge base, learn the common indications and contraindications of the various antidiabetic drug classes, follow the rules of prescribing a drug in a person with T2DM, and avoid slips and lapses of memory. The physician should avoid prescribing faults by carefully considering the indication/contraindication for a particular class of drug, its efficacy and appropriateness for a given person with T2DM, whether a drug from the same class is already on-board to avoid duplication, and the possibility of a drug–drug interaction with other drugs being prescribed for the management of associated comorbidities. Following this, the physician must be careful while writing the prescription to ensure that the correct dose, formulation, route, frequency, method of taking the drug, and duration of administration is legibly mentioned. For example, before prescribing metformin, it is essential to establish the indication for the medication, confirm that the person is not already receiving a therapeutic dose of metformin in some other fixed-dose antidiabetes drug combination, does not have major upper gastrointestinal symptoms limiting the use of metformin, and has an eGFR >30 mL/min. The physician should upgrade his or her skills by periodically attending various courses and CMEs to avoid knowledge-based errors in prescription. Improvement in systems and processes to reduce/avoid PEs should start with the identification and reporting of such errors, root-cause analysis in a blame-free environment, and modifying procedures to avoid a repeat of the same error. Appropriate use of computer-based e-prescriptions can contribute in reducing “prescribing faults” and errors in the actual writing of the prescription. In conclusion, PEs are very common in people with T2DM, both in the IP and OP settings. Such errors contribute to morbidity and occasionally might be responsible for mortality. It is essential to recognize and report such errors and do root cause analysis to avoid a repeat of the same error. Both physicians and the guardians of the systems/processes of healthcare facilities, need to work in tandem to reduce/eliminate PEs.