Kamila Dymala, PharmD, RPh, MBA, BCMTM, PACS

Tirzepatide (Mounjaro) is a novel drug for the treatment of type 2 diabetes in addition to diet and exercise to improve glycemic control for adults.

 It is a glucagon-like peptide-1 (GLP-1) receptor agonist with added glucose-dependent insulinotropic polypeptide (GIP). Dual GIP/GLP-1 agonist therapy demonstrated better glucose control and weight loss compared to selective GLP-1 receptor agonists in preclinical and clinical trials.

Both GLP-1 and GIP are classified as incretins and are expressed throughout the body, including pancreatic beta cells and the gastrointestinal tract. These stimulate insulin secretion in a glucose-dependent manner.

Incretins are a group of metabolic hormones that are released from the enteroendocrine cells into the bloodstream after eating and stimulate a decrease in blood glucose levels. There are 2 incretins produced: GIP and GLP-1.

GLP-1 and GIP increase insulin from beta cells and glucose uptake by muscles and decrease blood glucose. GLP-1 stimulates glucose dependent decrease of glucagon from alpha cells, lowering glucose production from the liver and decreasing blood glucose.

GIP promotes the growth and survival of the pancreatic beta cell and stimulation of adipogenesis. Dipeptidyl peptidase-4 (DPP-4) is a serine protease responsible for the inactivation of GLP-1 and GIP. In patients with type 2 diabetes, there is decreased GLP-1 and GIP production.

Tirzepatide’s protein sequence was based on the sequence of endogenous GIP and its pharmacological action on GLP-1 receptors is comparable to endogenous GIP. It is a 39 amino acid linear synthetic peptide conjugated to a C20 fatty diacid moiety.

The drug is also highly bound to albumin in the plasma, which prolongs its half-life.

 The long half-life of tirzepatide allows for a once-weekly dosing via subcutaneous administration. It is available in 6 doses: 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, 15 mg.

The mechanisms of action for tirzepatide include stimulation of first- and second-phase insulin secretion, as well reduced glucagon levels, both in a glucose-dependent manner. The drug delays gastric emptying, lowers fasting and postprandial glucose concentration, decreases food intake, and reduces body weight in patients with type 2 diabetes. In addition, tirzepatide increases insulin sensitivity.

The glycemic and weight control effects of this drug are believed to arise from dual agonism at GIP and GLP-1R. Studies have demonstrated that coadministration of a GIP and GLP-1R agonist significantly increases insulin response and suppresses glucagon secretion compared to separate administration of either hormone alone.

In clinical trials, tirzepatide was compared to semaglutide (GLP-1), insulin glargine and insulin degludec. Participants in the SURPASS-2 program achieved better average hemoglobin A1C reductions with tirzepatide than semaglutide.

In the SURPASS-3 program, tirzepatide was superior to titrated insulin degludec, with greater reductions in HbA1c and body weight at week 52 and a lower risk of hypoglycemia.

SURPASS-4 study evaluated patients with type 2 diabetes and elevated cardiovascular risk. Compared with glargine, tirzepatide demonstrated a greater and clinically meaningful HbA1c reduction with a lower incidence of hypoglycemia at week 52. Tirzepatide treatment was not associated with excess cardiovascular risk.

SURPASS-5 investigated the addition of subcutaneous tirzepatide, compared with placebo, to titrated insulin glargine among patients with type 2 diabetes and inadequate glycemic control despite treatment with insulin glargine. The study found that participants had statistically significant improvements in glycemic control after 40 weeks when the tirzepatide was added to the insulin glargine.

Research is ongoing on drugs that not only have a hypoglycemic effect, but also fight obesity and overweight. Antidiabetic drugs are gaining more interest among people who want to lose weight, also when excess body weight is not accompanied by diabetes, pre-diabetes, or insulin resistance.

In the recent study, the mean change in body weight was a key secondary endpoint and participants who were using tirzepatide lost between 12 lbs (5 mg) and 25 lbs (15 mg) on average. The study of people with diabetes who used tirzepatide found that they lost an average of 15% of their starting body weight.

The weekly injections of tirzepatide were tested in more than 2500 nondiabetic people who had a body mass index (BMI) exceeding 30 or over BMI 27 and had at least 1 chronic condition related to being overweight, such as high blood pressure, high cholesterol, or cardiovascular disease.

The study confirmed that people without diabetes lost an average of 15% to 20.9% of starting body weight in a 72-week, double-blind, randomized clinical trial. Participants administered placebo lost an average of 2.4 % to 3.1% of starting weight using the same advice and recommendations as the first group.

Study participants also received support to help them maintain a healthy diet with a daily deficit of 500 calories, as well as at least 150 minutes of physical activity per week. Although it certainly helped to reduce weight, it doesn't explain the scale of the weight loss seen in the study.

The type of weight loss we see when people exercise and change their caloric intake ranges from 5% to 7%. This study showed significantly greater weight loss (the average 15% to 20.9% weight loss) while using tirzepatide.

The most frequently reported adverse effects after tirzepatide were nausea, diarrhea and constipation. Because the drug is a GLP-1 agonist, it has not been studied in patients with a history of pancreatitis and is not indicated for use in patients with type 1 diabetes mellitus.

The Boxed Warning include thyroid C-cell tumors. Tirzepatide is contraindicated in patients with a personal or family history of medullary thyroid carcinoma or in patients with multiple endocrine neoplasia syndrome type 2. Tirzepatide delays gastric emptying, therefore it has the potential to affect the absorption of concomitantly administered oral medications.

Mounjaro. Prescribing Information. Lilly USA, LLC.

Rosenstock, J, et. al. Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial. Lancet. 2021;398(10295):143-155. doi: 10.1016/S0140-6736(21)01324-6.

Coskun T, Sloop KW, Loghin C, et al. LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: From discovery to clinical proof of concept. Mol Metab. 2018 Dec;18:3-14. doi: 10.1016/j.molmet.2018.09.009.

Frías JP, Davies MJ, Rosenstock J, et al. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes (SURPASS-2). N Engl J Med. 2021;385(6)(suppl):503-515. doi: 10.1056/NEJMoa2107519

Ludvik B, Giorgino F, Jódar E, et al. Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes (SURPASS-3): a randomised, open-label, parallel-group, phase 3 trial. Lancet. 2021;398(10300):583-598. doi: 10.1016/S0140-6736(21)01443-4

Del Prato S, Kahn SE, Pavo I, et al; for the SURPASS-4 Investigators. Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial. Lancet. 2021;398(10313):1811-1824. doi: 10.1016/S0140-6736(21)02188-7

Dahl D, Onishi Y, Norwood P, et al. Effect of subcutaneous tirzepatide vs placebo added to titrated insulin glargine on glycemic control in patients with type 2 diabetes: the SURPASS-5 randomized clinical trial. JAMA. 2022;327(6):534-545. doi:10.1001/jama.2022.007.

Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022 Jul 21;387(3):205-216. doi: 10.1056/NEJMoa2206038.

Articles

Dual GIP/GLP-1 agonist therapy demonstrated superior glucose control and weight loss in patients with diabetes compared to selective GLP-1 receptor agonists in preclinical and clinical trials.

Clinical Overview: Tirzepatide for Type 2 Diabetes

Rhabdomyolysis describes the rapid breakdown of striated muscle and is characterized by the rupture and subsequent necrosis of the muscle fibers. This, in turn, releases muscle cell components, such as myoglobin, lactate dehydrogenase, creatine kinase (CK) and electrolytes into the bloodstream and the extracellular space.

There are many factors that can lead to the onset of rhabdomyolysis. However, the most common cause is direct muscle damage, which can occur as a result of impacts, electric injuries, bites, crushes, hypothermia, hyperthermia, immobilization, improper tourniquet placement, convulsions, and electrolyte imbalances (hyponatremia, hypokalemia). Progressing ischemia or hypoxia promote the occurrence of myopathy.

Other factors that may contribute to the initiation of the rhabdomyolysis process may also include problems with the thyroid gland, genetic disorders such as muscular dystrophy or metabolic myopathies, and seizures.

One of the causes of rhabdomyolysis may be excessive exercise and muscle activity. This phenomenon can be observed after unusual or incorrectly performed physical exercises or be associated during extreme muscle activity, such as epilepsy. Muscle breakdown can also occur as a consequence of serious injury from major accidents.

The use of certain drugs, such as statins, may lead to rhabdomyolysis. An increased risk of myopathy and rhabdomyolysis may also occur with the concomitant use of CYP3A4 inhibitors, which leads to significantly increased plasma statin levels, in turn leading to considerable statin toxicity.

It is extremely important to remember the possibility of potential drug interactions of statins with other medicinal substances, and to pay special attention to patients who have just started the treatment. CYP3A4 inhibitors are often prescribed with statins and include fibrates (especially gemfibrozil), amlodipine, histamine H2 antagonists, clarithromycin, itraconazole, antidepressants, antiretroviral drugs (i.e., protease inhibitors), and immunosuppressive treatments, such as cyclosporine.

Statins are an effective class of drugs with lipid-lowering properties by inhibiting the activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. Medicinal substances belonging to this group of compounds are generally considered to be a very safe group of drugs.

The exact cause of myopathy from statin drugs is still unclear. There are many theories, including thesis concerning the lowered coenzyme Q10 synthesis process.

If patients taking blood lipid lowering medications complain of muscle pain or have had creatine kinase levels that exceed normal levels it is recommended to stop taking the medications and assess the patient for possible rhabdomyolysis. The use of drugs or other toxic substances, as well as the abuse narcotics and alcohol, can also play an important role in the occurrence of rhabdomyolysis.

These substances, through their toxic effect on muscle fibers, and indirectly through immobilization and compression or excessive activation of muscles, can be factors that trigger the process of their breakdown. Alcohol influence the inhibition of the process of calcium accumulation in the sarcoplasmic reticulum and cause negative influence on the membranes of muscle cells and inhibition of the sodium-potassium pump (Na + / K + ATPase), which is involved in maintaining cell integrity and may promote the phenomenon of muscle breakdown.

Rhabdomyolysis is characterized by a wide spectrum of symptoms, ranging from asymptomatic, such as an increase in plasma creatine kinase, through a significant increase in the level of biomarkers of acute kidney injury (AKI) in the blood and electrolyte imbalance, to disseminated intravascular coagulation.

The most common and characteristic symptoms of rhabdomyolysis include muscle pain, weakness, and the patient's characteristic dark urine. Increased excretion of myoglobin with urine is responsible for its dark color. Additional symptoms that occur frequently are muscle swelling, nausea, vomiting, and fever.

Myoglobin is a protein that mainly accumulates oxygen in the striated muscles. One myoglobin molecule carries one oxygen molecule. When the muscles are overstrained and lack oxygen, myoglobin releases it so that the muscles can work.

Myoglobin is filtered at the kidney glomerulus from where it enters the renal tubules. In rhabdomyolysis, myoglobin forms conglomerates, leading to renal tubules obstruction. The kidney vessels also contract, which may result in acute renal failure and the need for renal replacement therapy.

Occurring muscle pain, weakness, and myoglobinuria are defined as the set of symptoms that are characteristic of the rhabdomyolysis process. However, it has been observed that the described triad of symptoms occurs in fewer than 10% of patients.

When rhabdomyolysis occurs, myocytes are destroyed, and cell components are released into the circulation. When ATP is depleted in muscle cells (e.g. due to ischemia or intense exercise), the pumps (Na/K-ATPase and Ca-ATPase) are dysfunctional.

As a result, the intracellular ion balance (sodium and calcium) is disturbed, leading to an increase in the activity of proteolytic enzymes and/or osmotic edema, and ultimately even to the degradation and death of muscle cells. The content of cells is released, including myoglobin, potassium, CK, aldolase, lactate dehydrogenase, and aspartate aminotransferase.

Regardless of the cause that initiated the process of rhabdomyolysis in the patient's body, muscle damage results in elevated intracellular calcium levels, which in turn translates into protease activation and, ultimately, necrosis. The severity of rhabdomyolysis may be mild to life-threatening.

If the condition is severe, complications such as acute kidney injury (AKI), liver dysfunction, biochemical abnormalities, compartment syndrome, disseminated intravascular coagulation, cardiac arrhythmias, and even death may occur.

The final diagnosis of active rhabdomyolysis in the patient should be based on the results of laboratory tests, including the level of CK and serum myoglobin, as well as urine tests. The conducted clinical trials are very heterogeneous when it comes to the definition of the rhabdomyolysis process.

Most scientists qualify rhabdomyolysis as when the CK content exceeds the upper limit of the normal level by 5 times, with additional criteria in their diagnoses, such as accompanying muscle pain, general weakness, and edema. When patients suspected of rhabdomyolysis were taking lipid-lowering drugs (statins, fibrates or a combination), the CK cut-off point is considered to be 10 times the upper limit of normal.

Rhabdomyolysis treatment is symptomatic usually administering the fluids and dialysis to allow elimination of myoglobin and reducing the risk of renal complications. It is necessary to monitor and prevent complications of renal failure: hyperkalemia, elevated levels of uric acid, acidosis.

Pharmacists play a role in preventing of rhabdomyolysis through patient education during statin therapy as well as preventing drug-drug interactions. It is important to educate patients about appropriate fluid intake before and after strenuous exercise.

This will dilute the urine and help the kidneys eliminate the myoglobin that may have been released into the muscles during exercise. Pharmacists should encourage patients to always carry a full refillable bottle of water to ensure access to a drink and to see a physician if they experience muscle pain, weakness, have an infection or dark, tea colored urine.

Vanholder R, Sever MS, Erek E, Lameire N. Rhabdomyolysis. J Am Soc Nephrol. 2000 Aug. 11(8):1553-61.

Zutt R, van der Kooi AJ, Linthorst GE, Wanders RJ, de Visser M. Rhabdomyolysis: review of the literature. 

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Torres PA, Helmstetter JA, Kaye AM, Kaye AD. Rhabdomyolysis: pathogenesis, diagnosis, and treatment. Ochsner J. 2015;15(1):58-69.

Bosch X, Poch E, Grau JM. Rhabdomyolysis and acute kidney injury. 

The use of certain drugs, such as statins, may lead to rhabdomyolysis.

The Role of Pharmacists in Preventing Rhabdomyolysis 

Have you ever felt incompetent, despite the fact that those around you thought otherwise?

After a professional success or passing an exam, did you think that it was just luck that you succeeded?

Have you recently started a residency program and are worried that someone may find out that you don’t know something?

Have you recently been promoted to higher position, but feel that you don’t deserve it?

Have you ever felt that you won’t comment on some topics because you know too little about it and thought you will certainly embarrass yourself?

Imposter syndrome is a real challenge in pharmacy. The impostor phenomenon or imposter syndrome is described as a psychological experience of intellectual and professional fraudulence.

Individuals who experience these feelings may have the belief that others have inflated perceptions of their abilities and may be afraid of discovering their incompetence.

People who experience the impostor phenomenon believe that they are not worth their successes and doubt their knowledge, competence, and abilities.

The affected person feels out of place, unworthy of the successes, opportunities, and praise that befall them.

Imposter syndrome is not an official diagnosis in the Diagnostic and Statistical Manual of Mental Disorders (DSM–5); however, it is a real phenomenon, and it usually presents in certain situations—especially professional ones that we may perceive as stressful, challenging, or demanding.

Therefore, imposter syndrome is a phenomenon that affects self-confidence, significantly limiting the effectiveness of the professionals. This tendency has a negative impact on well-being and motivation, as well as reducing the effectiveness of action.

It represents excessively high expectations as to the standards we should achieve in knowledge and competence areas. The presence of the imposter syndrome is associated with:

Health care professionals may be affected by impostor phenomenon and the pharmacy profession is it not immune to that. Some self-report surveys presented that that those feelings were common among responding student pharmacists and faculty members.

A study shows that impostor phenomenon was common among undergraduates and pharmacy students. Moreover, the authors highlighted that the impostor phenomenon does not discriminate by education, age, gender, race/ethnicity, year in school, or academic major.

In another study, a survey on the prevalence of imposter syndrome among pharmacy residents indicated the residents have a significantly higher prevalence of imposter syndrome versus comparable groups.

A pilot study on the impostor phenomenon among medical students showed that it lead to professional burnout.

 Another study presented that perfectionism and the impostor are pertinent factors in the adjustment of health professional students, including medical, dental, nursing, and pharmacy students.

Those students experienced psychological distress, anxiety, and depression.

 The survey demonstrated positive associations between maladaptive perfectionism, impostor phenomenon, and suicidal ideation in medical students.

There are no direct studies to show how impostor phenomenon may affect practicing pharmacists. However, there are some publications about how negatively impostor phenomenon affects the mental health of medical students, residents, and physicians, as well as how medical culture can train for and/or exacerbate predispositions to develop impostor phenomenon.

The estimated percentage of people who may experience impostor phenomenon in the overall population is 70%.

 Previously, it was thought that women experience imposter syndrome more often.

Later research indicates that both men and women experience imposter syndrome.

 Environment or institutionalized discrimination, may play a major role in developing impostor feelings. The affected groups include racial or ethnic minorities, women in STEM fields, or even international students.

Health care professionals and students with imposter syndrome very often achieve great success. They are prone to perfectionism and set themselves with overly ambitious goals while fearing failure and enduring it much harder than other people; moreover, they do not get satisfaction from their successes.

They are also characterized by internal contradiction—on the one hand, they may need recognition and positive feedback from other people and on the other hand, they are not able to accept and fully believe in praise due to their negative self-image and low self-esteem.

Types of imposter syndrome are based on sets of destructive expectations adopted during the upbringing process. The first step in overcoming the imposter syndrome is to acknowledge what we are feeling and why it is happening.

Imposter syndrome was categorized it into 5 subgroups by Dr. Valerie Young, which include the 

Perfectionists, the Superman and Superwoman, the Natural Genius, the Soloists, and the Experts

Below are listed the destructive forms of expectations and beliefs with advice how to overcome them.

Perfectionists strive for flawlessness. Perfectionists set the bar very high for themselves and when they fail to achieve their goal 100% in every aspect, they begin to doubt themselves.

They are often convinced that other people will complete tasks less carefully than them, so they try to control everything around them strictly or do everything on their own.

Advice: If you recognize yourself or other people with perfectionism tendencies, begin to be more indulgent with the mistakes of yourself and others. Treat them as a natural part of learning and improving.

 are individuals who strive to be "the best" in all fields of action in life.

These types of people have ambitions to fulfill 100% in all roles in their lives, both professional and private. They force themselves to work beyond their strength to meet their exacting expectations. As a result, their relationships and health begin to suffer and they are at risk of burnout. Workaholics may become dependent on their environment to assess how they function in a given role.

Advice: It is important that people affected by this type of syndrome reflect on their expectations in the context of functioning in various roles and make a time balance sheet. What is real and what is not taking into account your rest and being in close relationships. It is also good for them to learn to accept constructive criticism not in person, but in relation to the task performed.

 is the belief that you may learn and do everything instantly, quickly and perfectly—sooner, faster, and better than others.

Brilliant people believe that it is important that the tasks are carried out, not only in the best possible and error-free manner, but also easily and quickly. If things don't come to them with the utmost ease and right away the first time, it is a failure for them.

Advice: Try to adopt a plan to improve your competences, recognizing that you will make many mistakes in the process. Make mistakes as a determinant on the way to your goal.

 may lead to imposter syndrome because individualistic systems urge people to pursue personal achievement, which creates competition between individuals and may lead to social anxiety.

Individualists are always carrying out tasks on their own. Collaboration or the necessary help from others is treated by the individualist as a sign of their weakness and lack of competence.

Advice: Start asking others for help and appreciate yourself for this type of behavior, treat it as acquiring new competences. People value and like other people more when they feel needed.

 want to know everything about a given topic.

Experts are mainly focused on getting all the knowledge on a given topic. In this situation, even a small lack of knowledge means failure and shame.

Experts have unrealistic expectations that they should know everything, they fear that they will be exposed. It is worth distinguishing here a healthy pursuit of development and learning new skills from an exaggerated tendency to constantly seek more knowledge, which is a form of procrastination.

Advice: Start becoming a mentor to others who have less knowledge and experience. Appreciate yourself for your competences—those you already have.

How we may overcome or reduce impostor syndrome?

It is worth realizing that our intelligence, skills, and competences are flexible abilities that we can broaden and deepen to a large extent. Failure and mistakes should not be a cause for shame and resignation, but can instead be seen as valuable guidance as to what can be improved and what we can work on to be even better.

It is natural that to achieve many of our ambitious goals, even those that initially seem unrealistic, we need to put forth significant effort, regardless of our level of intelligence or potential. The development of self-understanding, greater tolerance for one's own weaknesses, and the ability to sincerely appreciate ourselves for what we know can also play an important role.

If someone has entrusted us with a role or position, most likely they judged us as competent enough to be able to cope with this challenge. People who hired you or choose you for a position saw talent in you.

Do not doubt the intelligence of those who hired you, promoted you, or offered you a chance. They have made deliberate decisions based on your experience and potential—you really deserve to be there.

Other tips to overcome imposter syndrome include:

Choose someone you trust to tell them about your declining confidence and ask about additional support.

Take responsibility for your achievements and for your success.

When you achieve a goal or complete an important project, confirm out loud to yourself that it was achieved as a result of your talent and skill.

Examine everything you've gained and reflect on the hard work you've done to get where you are right now.

Practice listening to praise and wait for sincere compliments.

Listen carefully at what you say at loud and reduce negative self-talk.

Try mentoring—you have knowledge that you should share. Share it with someone who needs it. Not only will you notice how much you have to offer, but you will also discover your strengths during the process. Mentoring can reveal traits that you took for granted or mistakenly assumed were due to happiness. Besides, helping someone is a very empowering feeling.

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Boyle J, Malcom DR, Barker A, Gill R, Lloyd M, Bonenfant S. Assessment of impostor phenomenon in student pharmacists and faculty at two Doctor of Pharmacy Programs. 

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Imposter syndrome is a phenomenon that affects self-confidence, significantly limiting the effectiveness of professionals affected by it.

How to Overcome Imposter Syndrome in Pharmacy

Mineralocorticoid receptor antagonists (MRAs) also referred as aldosterone antagonists or anti-mineralocorticoids are class of drugs that block the effects of aldosterone.

Aldosterone synthesis, which occurs primarily in the adrenal gland, is modulated by multiple factors and may lead to oxidative stress, inflammation and organ fibrosis. Aldosterone binds to mineralocorticoid receptors in both epithelial (e.g., kidney) and nonepithelial (e.g., heart, blood vessels) tissues and increases blood pressure through induction of sodium reabsorption and potassium excretion. Mineralocorticoid receptor overactivation is a major driver of cardiovascular and kidney damage.

Aldosterone antagonists are important pharmacologic therapy in the neurohormonal blockade necessary in the treatment of hypertension and heart failure. Recent studies demonstrated that renal failure, proteinuria, and histologic renal lesions can be prevented by mineralocorticoid receptor antagonists.

Currently spironolactone, eplerenone, and finerenone are MRAs available for US patients. All drugs in class have similar mechanism of action as the potassium sparing diuretics the are competitively inhibiting mineralocorticoid receptors in the distal convoluted tubule to promote sodium and water excretion and potassium retention.

Table 1: Mineralocorticoid receptor antagonists comparison, structure, chemistry, distribution, and receptors affinity.

Spironolactone and eplerenone are steroidal MRAs but finerenone is a non-steroidal MRA. Spironolactone is non-selective MRA, however, eplerenone and finerenone are selective MRAs.

Spironolactone is a drug used as an add-on therapy in hypertension and New York Heart Association Class III-IV heart failure. It is used for a management of edema in cirrhotic adults not responsive to fluid and sodium restrictions. Additional indications include hyperaldosteronism and in nephrotic syndrome when treatment of the disease as well as fluid and sodium restriction with other diuretics is inadequate.

Spironolactone has antiandrogenic activity that leads to many of its off label uses, such as treatment of hirsutism, female pattern hair loss, and adult acne vulgaris.

Spironolactone is a drug used for its antiandrogenic effects in transgender female patients for reducing male-pattern hair growth.

The main contraindications to use the drug include hyperkalemia and Adison disease. The adverse effects (AEs) include gynecomastia, hyperkalemia,impotence, and menstrual irregularities.

Eplerenone is a compound similar to spironolactone; however, it is selectively binding to mineralocorticoid receptors relative to its binding to glucocorticoid, progesterone, and androgen receptors.

 Gynecomastia and hyperkalemia are less likely with eplerenone than spironolactone.

Finerenone is a dihydropyridine-based nonsteroidal mineralocorticoid receptor antagonist 

 to reduce the risk of kidney function decline, kidney failure, cardiovascular death, nonfatal heart attack, and hospitalization for heart failure in adults with chronic kidney disease (CKD) associated with type 2 diabetes mellitus (T2DM).

 By binding to the MR receptor, it reduces inflammation, fibrosis, and albuminuria in patients with diabetes and lowered the risk of first onset of kidney failure.

Finerenone blocks the mineralocorticoid receptor to reduce mortality and morbidity in patients with chronic severe congestive heart failure with an ejection fraction.

 It is distributed relatively equally between the heart and the kidney.

In comparison, spironolactone and eplerenone have higher concentrations in renal tissue than in cardiac tissue.

 Finerenone has no significant affinity or activity at androgen, progesterone, estrogen, and glucocorticoid receptors.

The drug binds selectively to the mineralocorticoid receptor and it is at least as potent as spironolactone with lower incidence of hyperkalemia and other AEs compared with both spironolactone and eplerenone.

 Finerenone was previously studied in the ARTS-DN randomized clinical trial to determine its efficacy on albuminuria in patients with diabetic nephropathy.

In another clinical trial, finerenone was associated with a reduction of a composite end point of all-cause mortality and heart failure outcomes in comparison to eplerenone.

The drug is currently investigated in study FINEARTS-HF to find its effect in heart failure with reduced ejection fraction and heart failure with preserved ejection fraction and in FIGARO-DKD to investigate the effect of medication on reducing cardiovascular mortality and morbidity with less advanced stages of CKD and T2DM.

Recent studies demonstrated that renal failure, proteinuria, and histologic renal lesions can be prevented by mineralocorticoid receptor antagonists.19Despite guideline-directed therapies, there remains a high unmet medical need in patients with CKD and T2DM, and there is increasing prevalence of patients with T2DM who are at risk for CKD.

The FIDELIO-DKD trial indicated that finerenone reduced the risk of cardiovascular and kidney failure outcomes in patients with and without a history of atherosclerotic cardiovascular disease. The results suggest that finerenone may represent an important treatment advance to reduce cardiovascular morbidity and mortality in patients with CKD and T2DM.

It may be recommended for reduction of the risk of sustained decline in glomerular filtration rate, end-stage kidney disease, cardiovascular death, heart attacks, and hospitalization due to heart failure in adults with CKD with T2DM. 

Finerenone is both a cardiovascular and kidney protective medication for individuals with T2DM and may be an option where SGLT2 inhibitors are not preferred.

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Recent studies demonstrated that renal failure, proteinuria, and histologic renal lesions can be prevented by mineralocorticoid receptor antagonists.