Cushing's syndrome, resulting from excessive cortisol levels, often presents with rapid weight gain and related health issues. Korlym (mifepristone) is a medication approved for managing hyperglycemia (high blood sugar) in adults with Cushing's syndrome, particularly those with type 2 diabetes or prediabetes, when surgery is not viable or has been ineffective. While not explicitly a weight loss drug, studies have shown that it can lead to weight loss in patients with Cushing's syndrome, which may translate into other positive health outcomes for these patients.
Understanding Cushing's Syndrome and Hypercortisolism
Cushing's syndrome is a rare endocrine disorder affecting an estimated 10 to 15 people per million annually, according to the American Association of Neurological Surgeons. It typically arises from a non-cancerous tumor in the pituitary or adrenal gland, leading to overproduction of cortisol, the body's primary stress hormone. Dr. Henry G. Fein, an endocrinologist at Sinai Hospital of Baltimore, notes that Cushing's syndrome significantly disrupts the body's natural chemical processes. Rapid weight gain is the most common symptom associated with Cushing’s syndrome. Diabetes, severe fatigue, weak muscles, high blood pressure, depression and other negative health problems are common in these patients as well.
Korlym: A Treatment Option for Hyperglycemia in Cushing's Syndrome
Korlym, containing the active ingredient mifepristone, received FDA approval in 2012 for treating hyperglycemia in Cushing's syndrome. While surgery remains the primary treatment, it's not always feasible, making Korlym a valuable alternative. Korlym is a brand-name oral tablet prescribed to treat hyperglycemia (high blood sugar) in adults with Cushing syndrome. It's approved for this use in adults who have type 2 diabetes or prediabetes, and surgery to treat Cushing syndrome has not worked or is not an option.
How Korlym Works
Mifepristone functions as a cortisol receptor blocker. Cortisol regulates many different body functions and works by binding to specific receptors (binding sites), which are present throughout the body. Korlym works by blocking cortisol receptors, which lowers cortisol activity. The way a drug works is known as its mechanism of action. Korlym’s active ingredient, mifepristone, competes with cortisol for binding to these receptors. This helps balance cortisol activity, reducing some of the negative effects of high cortisol levels in people with Cushing syndrome. By blocking cortisol's effects, Korlym helps regulate blood sugar levels and alleviate other Cushing's symptoms.
Dosage and Administration
The recommended starting dosage of Korlym is 300 mg, taken once per day with a meal. Your doctor may increase your daily dose in 300 mg amounts every 2 to 4 weeks as needed. For most people, the maximum daily dose is 1,200 mg. Taking Korlym at the same time each day helps maintain a consistent drug level in the body. The medication is intended for long-term use, provided it remains safe and effective for the individual.
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Clinical Evidence and Weight Loss
Clinical trials, including the SEISMIC study and its long-term extension, have demonstrated Korlym's effectiveness. The results, which include data on up to three and a half years of treatment, showed that patients experienced significant weight loss while taking Korlym, and they were able to keep the weight off, which may translate into other positive health outcomes for these patients. Patients in the SEISMIC trial experienced improvements in body weight, fat mass, and waist circumference, alongside enhanced insulin sensitivity. A follow-up study showed that the weight loss achieved during the initial 24-week treatment persisted for two additional years in patients who remained on therapy.
The CATALYST study, a phase 4 study, also demonstrated significant HbA1c reductions in a subset of eligible patients with difficult-to-control T2D and endogenous hypercortisolism. In the Treatment Phase of CATALYST, patients with endogenous hypercortisolism who received Korlym improved their body composition with weight loss and reductions in waist circumference.
Potential Side Effects and Precautions
Korlym can cause both mild and serious side effects. Common side effects include dizziness, nausea, fatigue, and headache. Serious side effects, though less common, can include adrenal insufficiency, decreased potassium, and QT prolongation (a type of irregular heart rhythm).
Boxed Warning: Korlym carries a boxed warning from the FDA regarding the risk of pregnancy loss. It is strictly contraindicated in pregnant women or those planning pregnancy.
Important Precautions:
- Inform your doctor about all medications, vitamins, and supplements you are taking.
- Do not take Korlym if you are taking certain medications for high cholesterol, such as simvastatin or lovastatin, or corticosteroid medications like prednisone.
- Report any unexplained vaginal bleeding, changes in the cells lining your uterus, or a history of endometrial cancer.
Personal Perspectives: Patient Stories
Personal stories highlight the transformative impact of Korlym. Angela, a Cushing's patient undiagnosed for 15 years, experienced a reversal of diabetes and improved mental well-being after starting Korlym. Mark, another patient, lost a significant amount of weight and regained energy levels he thought were lost forever. Pat was relieved when she finally learned that Cushing syndrome was causing her symptoms. But that was only the beginning of her treatment journey. Watch and learn how Korlym helped her regain lost energy and feel normal again.
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These narratives underscore the importance of accurate diagnosis and appropriate treatment for Cushing's syndrome.
Korlym and Metabolic Syndrome
Beyond Cushing's syndrome, research suggests Korlym may have potential benefits in treating metabolic syndrome, a cluster of conditions that increase the risk of heart disease, stroke, and type 2 diabetes. Studies in rodents and humans with metabolic syndrome have shown beneficial effects of mifepristone. Metabolic syndrome is a group of physiologic, biochemical and metabolic factors that lead to increased risk for type 2 diabetes, stroke and cardiovascular diseases. These factors (visceral obesity, dyslipidemia, hyperglycemia and hypertension) are associated with changes in lifestyle, mainly in dietary preferences and sedentary behavior. Insulin resistance is a major underlying mechanism of metabolic syndrome, which affects different organs such as the brain, liver, pancreas, vascular endothelium, adipose tissue, heart and skeletal muscle, which contribute to development of metabolic syndrome. However, further research is needed to fully understand its role in this context.
Alternatives to Korlym
There are not yet any other drugs similar to Korlym. Treatment of hyperglycemia (high blood sugar) caused by high cortisol levels in people with endogenous Cushing syndrome will involve either managing the blood sugar or cortisol. The following drugs may be prescribed to manage high blood sugar in people with type 2 diabetes or prediabetes: metformin (Glumetza), insulin therapy, GLP-1 receptor agonists, such as semaglutide (Ozempic, Rybelsus) and dulaglutide (Trulicity), SGLT2 inhibitors, such as empagliflozin (Jardiance) and dapagliflozin (Farxiga), DPP-4 inhibitors, such as sitagliptin (Januvia) and linagliptin (Tradjenta). The following drugs may be prescribed to manage cortisol levels in people with endogenous Cushing syndrome: pasireotide (Signifor, Signifor LAR), cabergoline, levoketoconazole (Recorlev).
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