Benchmark-Approved Drug by FDA

Benchmark-Approved Drug by FDA

While drugs are commonly used in various clinical scenarios to manage various conditions, it`s worth noting that the same drugs can be poisons and cause harmful effects if regulations and guidelines are not followed. To ensure safety, efficacy, and protection of the public against exposure to harmful drugs, the US government established a food and drug administration (FDA) board (Darrow et al., 2021).

FDA is mandated to ensure that drug products are safe for human use. Therefore, a newly discovered drug must undergo a rigorous process involving various phases of trial before approval for use while undergoing continuous monitoring where unsafe drugs are unapproved for use (Sha et al., 2020).

Because of the recent increase in cardiovascular events in patients with diabetes mellitus type 2 (T2DM), researchers undertook a series of studies to come up with an agent that could lower the risk of heart failure. Among the various agents, empagliflozin has recently been approved for that function.

Description of the Disease

Diabetes mellitus is a metabolic disorder characterized by high glucose levels in the body. In T2DM, there is resistance to insulin usage by the body leading to a disturbance in glucose control (Cho et al., 2018). As a result, patients present with signs and symptoms that require interpretation to make a diagnosis. The common symptoms include polyuria, polydipsia, polyphagia, and weight loss.

In addition, other non-specific symptoms such as blurry vision, nausea, vomiting, abdominal pains, poor healing of wounds, and recurrent infections, among others (Cho et al., 2018). Even with these symptoms, laboratory tests are paramount for diagnosis and management. Among the common tests done for diagnosis include blood sugar levels and hemoglobin A1C levels (HbA1C).

The diagnosis criteria for diabetes involves random blood sugar level (RBS) > 11.0 mmol/l; fasting blood sugar (FBS) >7.1mmol/l; 2-hour postprandial oral glucose tolerance test (OGTT) > 11.0 mmol/l with symptoms and HbA1C > 6.5% (Castañeda et al., 2021). Once a diagnosis is made, treatment is tailored to control blood sugars while reducing complications.

While blood sugar control is the aim of management, some patients still experience complications related to diabetes. Complications arise due to microvascular and macrovascular effects of diabetes. Common microvascular complications include diabetic retinopathy, neuropathy, and nephropathy. On the other hand, macrovascular complications majorly comprise cardiovascular disease (Cho et al., 2018).

Common cardiovascular diseases include stroke, heart failure, myocardial infarction, and diabetic cardiomyopathy, among others. Compared to the general population, patients with diabetes have an increased two-fold risk of developing cardiovascular diseases (Kenny & Abel, 2019).  Diabetes causes cardiac hypertrophy that causes cardiomyopathy and increases the risk of heart failure either with reduced ejection fraction or preserved ejection fraction.

In addition, diabetes is associated with increased myocardial fatty acid utilization, decreased cardiac efficiency, decreased utilization of glucose, and increased myocardial consumption of oxygen. In heart failure, the heart fails to pump blood to other body systems leading to compromised states with a risk of hypoxia and ischemia (Sha et al., 2020).

Consequently, the presence of cardiovascular conditions presents a clinical challenge in terms of clinical outcomes while increasing the risk of mortality, hospitalization, and complications. Unlike many antidiabetic agents that reduce blood sugars, empagliflozin not only reduces blood sugar but also reduces the risk of cardiovascular events.

Description of the Drug

Empagliflozin is an antidiabetic agent classified as a sodium-glucose cotransporter two inhibitors (SGLT2i). It inhibits the SGLT2, thus inhibiting glucose reabsorption with resultant glycosuria and treatment of T2DM (Kenny & Abel, 2019). It was approved for glucose control in 2014; however, following a series of trials with various studies conducted, the drug was found to reduce the risk of cardiovascular mortality, heart failure hospitalization, and reduction in adverse outcomes in patients with DM (Maddern, 2021).

It was approved in August 2021 for its significance in cardioprotection. The exact mechanism is not fully understood; however, various mechanisms have been proposed. Such include reduced blood pressure, increased natriuresis, a modest reduction of circulating ketones, and protection of the renal system (Castañeda et al., 2021).

In addition, it reduces the reabsorption of sodium in the proximal tubule while increasing the delivery of sodium to the distal tube; this influences physiological function with a resultant decrease in pre- and afterload in the heart and downregulation of the sympathetic activities.

In terms of pharmacokinetics, it undergoes the processes of absorption, distribution, metabolism, and elimination like other agents. It is rapidly absorbed, reaching its peak plasma concentration within an hour and a half. It is then distributed while bound to protein at 88.2%  (Kenny & Abel, 2019).

Metabolism is majorly carried out in the liver through glucuronidation by the uridine 5`-diphospho-glucuronosyltransferases UGTA3, UGTA8, UGT2B7, and UGT1A9 which form glucuronide conjugates. Finally, it is eliminated through urine and feces with a half-life of twelve hours.

Risk and Monitoring

While empagliflozin has proven useful in reducing cardiovascular disease, its use may be limited in various populations due to side effects and interactions with other agents; these warrant monitoring of individuals using this agent. Because SGLT2i agents cause glycosuria, there is a risk of hypoglycemia when taking such agents. Therefore, monitoring of blood using a glucometer and assessing for signs of hypoglycemia such as tremors, sweating, confusion, reduction in the level of consciousness, and palpitation is paramount in patients taking empagliflozin (Maddern, 2021).

In addition, loss of sodium in urine results in concurrent water loss. As a result, increased water loss through urination predisposes an individual to hypovolemia. Hypovolemia may result in reduced blood pressure, orthostatic hypotension, and acute kidney injury caused by pre-renal hypovolemia. Therefore, blood pressure should be checked regularly while advising patients to avoid abrupt standing from a sitting position unless with support.

Also, serial urea, creatinine, and electrolyte testing should be carried out to detect any electrolyte imbalances and assess kidney functions. To reduce the risk of hyponatremia, patients should take adequate table salt.  Besides, the risk of dehydration is also increased with ongoing water loss. Patients may present with dizziness, confusion, oliguria, and excessive thirst. Adequate water intake is paramount in these patients to reduce the risk of dehydration.

Ketoacidosis is also another side effect that has been reported in patients taking this agent. It presents with nausea, confusion, stomach pain, drowsiness, vomiting, and difficulty breathing (Kenny & Abel, 2019). Therefore, various factors that could predispose patients to ketoacidosis should be identified before initiating therapy. (Ryan et al., 2018). Blood and urine testing for ketones should be performed regularly to monitor ketone levels and help in management.

In addition, women have an increased risk of bladder infection and yeast infection. Besides, allergic reactions are likely to develop in patients allergic to this agent. Therefore, complete history, including allergic history, should be taken to avoid prescribing this agent to hypersensitive individuals. Finally, drug history should be sought due to interactions existing between empagliflozin and other agents.

Taking empagliflozin with diuretic agents such as loop diuretics could potentially lead to increased water loss with resultant fluid imbalance and electrolyte imbalances (Richardson et al., 2021). On the other hand, using insulin or other antidiabetic medications with empagliflozin requires close monitoring due to the risk of hypoglycemia.

Comparison with other Agents

            Compared to other antidiabetic agents that have a cardioprotective function, empagliflozin has been associated with better clinical outcomes that warrant its prescription in patients with diabetes. For instance, metformin, apart from lowering glucose control, has shown a reduction in myocardial infarction and reduction in mortality when compared to patients treated otherwise (Darrow et al., 2021).

Despite reducing cardiac hypertrophy, metformin causes cardiac fibrosis, which may hinder its use in reducing cardiovascular diseases in patients with diabetes. In addition, metformin only reduces myocardial utilization of fatty acids without a change in glucose utilization, as reported with the use of empagliflozin (Kenny & Abel, 2019).

On the other hand, despite sulfonylureas being effective in controlling blood sugars, little has been shown about its effects on cardiovascular protection. It has also been attributed to weight gain that could predispose to increased cardiovascular diseases (Maddern, 2021).

Therefore, considering all the factors, empagliflozin is feasible in clinical practice with a reduction in cardiovascular risk, reduced hospitalization, and improved health outcomes (Richardson et al., 2021). I prefer to prescribe empagliflozin to patients to improve clinical outcomes and reduce the burden caused by diabetes mellitus.

Conclusion

With the ever-increasing incidences of diabetes mellitus worldwide, complications arising from diabetes continue to cause adverse health concerns. Among the complications, diabetes increases the risk of heart failure and other cardiovascular conditions compared to non-diabetes cases. Using empagliflozin has provided some clinical importance in controlling blood sugars and reducing the risk of cardiovascular diseases. This has helped in improving clinical outcomes as well as reducing mortality and morbidity, the factors that warrant its use.

References

Castañeda, A. M., Dutra-Rufato, A., Juarez, M. J., Grosembacher, L., Gonzalez-Torres, H., & Musso, C. G. (2021). Sodium-glucose cotransporter 2 inhibitors (SGLT2i): renal implications. International Urology and Nephrology, 53(2), 291–299. https://doi.org/10.1007/s11255-020-02585-w

Cho, E. H., Park, S.-J., Han, S., Song, J. H., Lee, K., & Chung, Y.-R. (2018). Potent oral hypoglycemic agents for microvascular complication: Sodium-glucose cotransporter 2 inhibitors for diabetic retinopathy. Journal of Diabetes Research, 2018, 6807219. https://doi.org/10.1155/2018/6807219

Darrow, J. J., Dhruva, S. S., & Redberg, R. F. (2021). Changing FDA approval standards: Ethical implications for patient consent. Journal of General Internal Medicine, 36(10), 3212–3214. https://doi.org/10.1007/s11606-021-06762-0

Kenny, H. C., & Abel, E. D. (2019). Heart failure in type 2 diabetes mellitus: Impact of glucose-lowering agents, heart failure therapies, and novel therapeutic strategies. Circulation Research, 124(1), 121–141. https://doi.org/10.1161/CIRCRESAHA.118.311371

Maddern, G. (2021). Ethical approval: unfit for purpose? ANZ Journal of Surgery, 91(11), 2236. https://doi.org/10.1111/ans.17276

Richardson, C. R., Borgeson, J. R., Van Harrison, R., Wyckoff, J. A., Yoo, A. S., Aikens, J. E., Griauzde, D. H., Tincopa, M. A., Van Harrison, R., Proudlock, A. L., & Rew, K. T. (2021). Management of Type 2 Diabetes Mellitus. https://www.ncbi.nlm.nih.gov/books/NBK579413/

Ryan, P. B., Buse, J. B., Schuemie, M. J., DeFalco, F., Yuan, Z., Stang, P. E., Berlin, J. A., & Rosenthal, N. (2018). Comparative effectiveness of canagliflozin, SGLT2 inhibitors, and non-SGLT2 inhibitors on the risk of hospitalization for heart failure and amputation in patients with type 2 diabetes mellitus: A real-world meta-analysis of 4 observational databases (OBSERVE-4D). Diabetes, Obesity & Metabolism, 20(11), 2585–2597. https://doi.org/10.1111/dom.13424

Sha, W., Wen, S., Chen, L., Xu, B., Lei, T., & Zhou, L. (2020). The role of SGLT2 inhibitor on the treatment of diabetic retinopathy. Journal of Diabetes Research, 2020, 8867875. https://doi.org/10.1155/2020/8867875

Benchmark-Approved Drug by FDA Instructions

Choose a drug that has been approved by the FDA within the past year.

Write a 1,000-1,250 word paper in which you:

Describe the drug approved by the FDA. Include the pharmacodynamics and pharmacokinetic properties of the chosen drug.
Provide an overview of the disease state for which the drug is used.
Describe what is different about this agent compared to currently available therapies.
Discuss the potential risks associated with this agent and any monitoring parameters that are necessary.
Decide whether you would personally prescribe this agent or stick with currently available alternatives.
You are required to cite 5-10 sources to complete this assignment. Sources must be published within the last 5 years and appropriate for the assignment criteria and nursing content.

Prepare this assignment according to the guidelines found in the APA Style Guide, located in the Student Success Center. 

This assignment uses a rubric. Review the rubric prior to beginning the assignment to become familiar with the expectations for successful completion.

You are required to submit this assignment to LopesWrite. A link to the LopesWrite technical support articles is located in Class Resources if you need assistance.

Benchmark Information

This benchmark assignment assesses the following programmatic competencies:

MS-NUR-ACNP / MS-NUR-FNP

6.3: Assess the pharmacodynamics and the pharmacokinetic impact of pharmacologic therapies in the treatment of diseases and altered states.