The potential for GLP-1 drugs such as Ozempic and Wegowy, and new anti-cancer and Alzheimer’s drugs to totally wreck the Financial Stability (such as it is) of Medicare, Medicaid and the US Healthcare in general.
An informed opinion from a practicing physician and medical officer at several pharmaceutical companies
Donald H. Marks, M.D., Ph.D.
Physician, Scientist, 3rd gen vet
Morris County, NJ
The diabetic drug Ozempic (semaglutide, Novo Nordisk) is a member of the GLP-1 receptor agonist class of medication. It originally was found useful along with diet and exercise to improve blood sugar (glucose) control in adults with type 2 (but not Type 1) diabetes (Shi 2018). Ozempic acts as a GLP-1 receptor agonist that selectively binds to and activates the GLP-1 receptor, the target for native GLP-1. GLP-1 is a physiological hormone that has multiple actions on glucose, mediated by the GLP-1 receptors. Its use can result in a statistically significant reduction in HbA1c, a marker for diabetes, compared with placebo, and is the basis for its original approved clinical indication. Further, when formulated at a higher dose level than in the product Ozempic for diabetes control, semaglutide sold under the product name of Wegovy can be instrumental in weight loss.
Type2-Diabetes.png (900×677) (researchoutreach.org)
Ozempic has recently had its indications widened to include reducing the rate of cardiac death, based upon the clinical research of Ghusn et al (2022). Call me a skeptic, but I have to wonder whether there is any reason to think that the effort to support clinical studies for widened indications of the already immensely profitable Ozempic is really just a marketing grab, rather than a fortuitous discovery of a new therapeutic use of Ozempic?
The product information for semaglutide now claims that its use will lower the risk of major cardiovascular events such as stroke, heart attack, or death in adults who also have known heart disease. It certainly would appear that the expansion of indications for semaglutide to include the reduction of cardiac death rates is based on clinical evidence rather than just marketing efforts. The FDA approved the use of semaglutide for this added clinical indication / purpose after a clinical study showed that semaglutide lowers the risk of major cardiac events by as much as 20% in people with obesity or overweight and cardiovascular disease. This study, known as the SELECT trial, was significant because it was the first to show that Wegovy, which contains a higher dose of semaglutide than Ozempic, also lowers the risk of heart disease even in people who don’t have diabetes.
The approval of the expanded indication for use beyond diabetes appears to be the result of rigorous clinical trials and research. The widened indications are indeed backed by scientific findings. The SELECT trial’s results are considered a major breakthrough in cardiovascular and obesity medicine, highlighting the potential of semaglutide to benefit a large number of Americans who fit the expanded criteria.
It’s important to note that while pharmaceutical companies do engage in marketing their products, the FDA’s approval process for new indications of a drug is based on the evaluation of scientific evidence of both safety and efficacy from clinical trials (Mattina 2024). I am confident that the decision to widen the clinical indications of all very expensive medications like semaglutide to include the prevention of cardiovascular events was made after careful consideration of the benefits and risks demonstrated in these studies.
My professional background gives me some basis to understand the issues involved. I am a Board-certified internal medicine physician (UCLA) and have been practicing medicine for 40 years. I also have a Ph.D. in Microbiology, from the (now) Department of Microbiology Immunology and Medical Genetics at UCLA. I have published scientific studies in major peer-reviewed medical journals and I also hold five biomedical patents. I have been the associate director of adult drug research at Hoffman LaRoche Pharmaceuticals and the director of adult vaccine research at Avantis Pasteur vaccines company.
Besides the pluses of semaglutide with respect to better diabetes control, weight loss and reducing cardiovascular disease, like all medications, the clinical use of semaglutide can result in a number of common side effects, including:
nausea, vomiting, diarrhea, stomach (abdominal) pain, and constipation.
Use of semaglutide may also cause a number of serious side effects, including:
inflammation of the pancreas (pancreatitis), exhibited by severe pain in the stomach area (abdomen) that will not go away, with or without vomiting.
changes in vision.
low blood sugar (hypoglycemia). The risk for getting low blood sugar may be higher if Ozempic is used with with another medicine that can cause low blood sugar, such as a sulfonylurea or insulin. Signs and symptoms of low blood sugar may include: dizziness or lightheadedness, blurred vision, anxiety, irritability or mood changes, sweating, slurred speech, hunger, confusion or drowsiness, shakiness, weakness, headache, fast heartbeat, and feeling jittery.
kidney problems (kidney failure). In people who already have kidney problems (not uncommon in diabetics), diarrhea, nausea, and vomiting may cause a loss of fluids (dehydration), which may cause kidney problems to get worse.
serious allergic reactions, with signs such as swelling of the face, lips, tongue, or throat; problems breathing or swallowing; severe rash or itching; fainting or feeling dizzy; or very rapid heartbeat.
gallbladder problems, manifesting such as pain in the upper stomach (abdomen), fever, yellowing of the skin or eyes (jaundice), or clay-colored stools.
Warnings and Precautions against semaglutide, described in the official FDA-approved prescribing information, include the potential to develop:
• Pancreatitis: 
• Diabetic Retinopathy
• Hypoglycemia: Concomitant use with an insulin secretagogue or insulin may increase the risk of hypoglycemia, including severe hypoglycemia. Reducing dose of insulin secretagogue or insulin may be necessary (5.5).
• Acute Kidney Injury: Monitor renal function in patients with renal impairment reporting severe adverse gastrointestinal reactions (5.6).
• Hypersensitivity Reactions: Serious hypersensitivity reactions (e.g., anaphylaxis and angioedema) have been reported.
• Acute Gallbladder Disease: If cholelithiasis or cholecystitis are suspected, gallbladder studies are indicated.
There are a number of negative implications of Medicare and Medicaid widening the approved uses of semaglutide beyond control of diabetes and weight loss, for the new cardiovascular indications. This could severely negatively impact both Medicare and Medicaid spending (Williams 2023). Potential implications include changes in drug costs, utilization patterns, and health outcomes. The following areas will need to be studied;
Cost-effectiveness assessments: Evaluating the cost-benefit ratio of semaglutide for new indications.
Impact on beneficiaries: How will expanded access affect patients’ health and well-being?
Reimbursement models: Ensuring alignment between Medicare and Medicaid payment structures.
Equity: Addressing disparities in access and affordability. This is already a major problem for many basic essential meds, including insulin, cardiovascular, chemotherapy and Alzheimer’s disease..
These considerations are similar to those for other new and potentially budget-busting drugs, such as for cancer and Alzheimer’s.
The financial implications of widening semaglutide approval for new indications would depend on various factors, including reimbursement policies, patient outcomes, and overall health system performance. As discussed by Cubanski 2021 concerning new meds for Alzheimer’s, for comparison, although it is hard to know exactly how many Medicare beneficiaries will take Aduhelm for Alzheimer's, even a conservative estimate would lead to a substantial increase in Medicare spending. In 2017, nearly 2 million Medicare beneficiaries used one or more of the currently-available (and in my opinion not all that effective) Alzheimer’s treatments covered under Part D, based on Medicare Part D claims data. If just one-quarter of these beneficiaries would be then prescribed Aduhelm, approx. 500,000 beneficiaries, and Medicare pays 103% of $56,000 for Audhelm per year in the near term, then the total spending for Aduhelm in just one year alone would be nearly $29 billion. This expense, paid by Medicare and the patients who use this drug, would be an amount that would far exceed spending on any other drug covered under Medicare Part B or Part D, based on 2019 spending. To put this $29 billion amount in context, total Medicare spending for all Part B drugs was $37 billion in 2019. This does not include of course, treatment of known and potential adverse events of using Aduhelm, including serious severe and fatal side effects like intercranial bleeding.
In summary, I definitely agree with The Commonwealth Fund that it is certainly essential to balance healthcare nnovation with sustainability and equitable access.
References
Ozempic, Prescribing Information.
Cubanski J https://www.kff.org/medicare/issue-brief/fdas-approval-of-biogens-new-alzheimers-drug-has-huge-cost-implications-for-medicare-and-beneficiaries/ 2021
Ghusn W et al. Weight Loss Outcomes Associated With Semaglutide Treatment for Patients With Overweight or Obesity. JAMA Netw Open. 2022 Sep 1;5(9):e2231982.
Lewis C et al. The Impact of the Payment and Delivery System Reforms of the Affordable Care Act | Commonwealth Fund. 2022
Mattina C FDA Approves Semaglutide to Prevent Heart Events in Patients With CVD and Excess Weight (ajmc.com) 2024
Shi FH et al. Efficacy and Safety of Once-Weekly Semaglutide for the Treatment of Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Front Pharmacol. 2018 Jun 4;9:576.
Williams E et al. Medicaid Utilization and Spending on New Drugs Used for Weight Loss | KFF 2023.
A few Related publications by the author:
3. Reducing The Influence of Politics in Healthcare by DH Marks
4. Drug Utilization, Safety and Clinical Use of Actos and Avandia. Int J Risk Saf Med. 2013 Jan 1;25(1):39-51. Review by DH Marks
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