The Ultimate Key Opinion Leader?

Key Opinion Leader or KOL is an interesting myth. In the long era of the pharmascolds, it was frequently stated that all you needed to successfully market a drug was a KOL paid by the company to sell it to the unknowing clinicians who were just waiting to prescribe in lock step with whatever was suggested.  KOLs were typically academics with research and lecturing credibility but also included clinicians who may have had some experience with the drug in clinical trials. The KOL/clinician interface frequently occurred over pharmaceutical company sponsored CME events or meals. KOLs in psychiatry were treated more harshly than those in any other field when a US Senator decided to investigate their individual employment arrangements. An explanation was never given about that selectivity, but I did notice some other specialists were added – probably for cover.

The myth of KOL as Pied Piper encouraging mass prescriptions always struck me as absurd for several reasons.  First, I know the psychiatrists.  It might be possible that the psychiatrists I know are more enlightened than most – but my contact with them in numerous clinic, hospital, academic and non-academic settings treating diverse groups of patients makes that unlikely. As a group they are looking for inexpensive continuing medical education (CME) credits, hearing about the latest developments, and getting better treatments to their patients. Better in this case means more efficacy, fewer side effects, or both.  With direct-to-consumer advertising in the US, patients coming to appointments requesting a new drug is a common occurrence and a fast way to learn about those drugs was listening to a KOL and picking up an FDA approved package insert at the same time. That confluence of factors can make it seem like this is all a great conspiracy that includes physicians – but it is not.  The clinicians involved are as skeptical about new drugs as they want something that works better. Second, pharmaceutical companies aggressively market drugs.  Most physicians are aware of this and the fact that people in the US pay much more for medications than is paid anywhere else in the world. Most physicians are also aware of the mechanisms that lead to those higher prices and must deal with the administrative costs and their patients going without needed medications.  Third, physicians have limited control over the prescription of newly released expensive drugs.  Rationing these drugs is a separate for-profit business.  Those businesses have gone as far as rationing low cost generic medications and they will make it painful for any physician to prescribe a new medication if there are cheaper alternatives.  Fourth, working as a KOL (or more probably a sponsored lecturer) can give a sense of satisfaction in terms of continuing use of basic science and discussions with experts.  All these factors lead to skepticism rather than uncritical acceptance of a sales pitch. I don’t know of any celebrity level psychiatrist who could endorse a pharmaceutical product that would lead it to be immediately and universally adopted. 

That leads me to the Ultimate KOL (UKOL).  For the past few weeks Oprah Winfrey has been in the news for a significant and visible weight loss. There was immediate suspicion in the gossip media that she was using weight loss drugs – specifically glucagon-like peptide (GLP-1) agonists.  She initially said that she lost the weight with the usual methods and that using a drug would be “cheating”.  She has had similar weight losses in the past and in one case ran the New York City marathon.   The photo of her at the top of this post was for her 50^th birthday when she lost all the weight through diet and exercise. More recently - she was at an opening and said she did use a medication and added that she was tired of being shamed for excessive weight and being treated differently at a higher body weight than a lower body weight.  She has not disclosed the name of the medication.

Oprah has unique status as a celebrity. According to Time magazine - she was one of three and four most influential people in the 20th and 21st century respectively (1).  She had a product endorsement segment on her daily show called Oprah’s Favorite Things that greatly increased sales for many products.  Her endorsement of Barack Obama produced an additional 1 million votes in the Democratic primaries (2). At first glance, Oprah’s statement about weight loss medication seems consistent with her past promotions of products, books, and her self-improvement brand. 

In this case things are a bit more complicated.  In October 2015, she purchased 6.4 million shares or $43.2 million ($6.79 a share) of Weight Watchers (WW) stock.  She sold about a million shares when the stock appreciated and was given an option to purchase an additional 3.3 million shares. (5).  According to the latest SEC document WW is in a Strategic Collaboration Agreement with Oprah that began in 2015 that has been extended to 2025.  In the annual report she is listed as one of 9 Directors.  Her last stock purchase was in January and April of 2023 (5,067 and 2,053 shares respectively). In April of 2023 Weight Watchers acquired the telehealth company Weekend Health/Sequence described in their press release as “a subscription telehealth platform offering access to healthcare providers specializing in chronic weight management.”  They now offer weight loss medications including GLP-1 agonists directly through their web site.  I did not go through the process because a name was required, but several sources suggest this is a monthly subscription service

Prior to Oprah’s self-disclosure demand for GLP-1 agonists was very high and there was concern that weight loss demand would reduce availability of these medications for people with diabetes mellitus.  Some medications are approved for weight management only and others for treating diabetes mellitus only. During the last 3 months of 2022 there were and estimated 9 million prescriptions for both branded version of semaglutide - Ozempic and Wegovey.  At the time, the average cost of Ozempic was about $800/month and Wegovey was $270/week.  Doing the arithmetic, at that rate of prescribing the costs of these prescriptions could easily exceed $100 billion per year. That would make them the highest selling drugs of all time.

GLP-1 agonists are unique medications.  They have a polypeptide structure and a much higher molecular weight than typical medications.   That protein structure makes them more likely to trigger antibody formation and an immune response.  The main side effects are gastrointestinal – nausea, vomiting, diarrhea, constipation and abdominal pain and a significant number of patients in the clinical trials withdrew due to these side effects.  Hypoglycemia can be a problem especially if there is concurrent oral hypoglycemic use. Dehydration is also a common problem accompanying acute weight loss and starvation. That combination of problems leads to a warning about needing to monitor for dehydration in patients being treated with these medications especially because there is a higher incidence of renal damage in that patient group.  There are warnings about pancreatitis, thyroid C-cell carcinoma, acute renal injury, diabetic retinopathy complications, and hypoglycemia. There was also a recent report of increasing calls to poison control centers about semaglutides and counterfeit products. The therapeutic effects of these drugs include glycemic control and weight loss although most of these drugs have an indication for Type 2 diabetes mellitus only.  

I plan a more detailed post on the standard and more interesting pharmacological properties of these medications in the new year.  So far, I have compiled a table and will be working from an enhanced version of that.  The goal of this post is to document the effect of who is probably the single most important influencer in American society and her impact on the sales of this class of medication in the United States. Just the events that have occurred so far will probably be far reaching – limited only by the supply and the availability of prescribers.  I expect that there will be many online prescribers available since the advent of telemedicine has led to specialty prescribing of a few drugs to many recipients.   

There are currently unanswered questions.  Will Oprah disclose the medication she used?  Will she endorse a specific drug?  We have recently seen Kareen Abdul Jabbar in NOAC commercials for apixaban.  Secondarily – how will this issue be studied?  The typical studies that purported to show that physicians were influenced by trinkets or KOLs were poorly done and any increase in prescribing was taken as evidence of influence.  How can the Oprah factor be studied to reduce confounders like the American fantasy of weight loss without effort or the debate that being overweight or obese is a disease rather than a personal responsibility. From an ethical standpoint, are there problems with conflict of interest given the share that Oprah has in a company that is promoting and profiting from weight loss drugs?  The scale of potential profit is enormous compared with what most physicians are reported to the CMS Open Payments database.  In 2022, the median payment to physicians who received payments from pharmaceutical manufacturers or device makers was $161.  

For the record, at this point I am completely neutral on the issue of GLP-1 agonists for weight loss. I am very familiar with the previous literature and pharmacology of weight loss drugs.  I was an early witness to the failed attempt to use stimulants to treat obesity and treated many of those patients for amphetamine dependence. It is clear to me that there is a lot of hype about these medications right now and how they are the best medications ever invented to treat obesity. Since the previous medications were mildly effective to not effective that is a low bar.  Just reading the available package inserts suggests to me that a significant number of people will not be able to tolerate them and many will probably tolerate significant side effects to maintain a lower body weight. And with all new medications, the real question is what happens to the population taking the drug with wider and longer exposure.  Will there be adverse effects not seen in shorter clinical trials?  So, stay tuned for more detailed pharmacology and theory about the GLP-1 agonists.  In the meantime, see if Oprah has a palpable impact on the market. My guess is that her effect will easily surpass any thousand or more physician lecturers and KOLs.  

George Dawson, MD, DFAPA

References:

1:  Garthwaite CL. You Get a Book! Demand Spillovers, Combative Advertising, and Celebrity Endorsements. National Bureau of Economic Research; 2012 Mar 15.

2:  Garthwaite C, Moore T. The role of celebrity endorsements in politics: Oprah, Obama, and the 2008 democratic primary. Department of Economics, University of Maryland. 2008 Sep:1-59.

3:  O'Connell B.  Oprah's Weight Loss Company Adds a Prescription Drug Feature.  May 7, 2023.  https://www.thestreet.com/personalities/oprahs-weight-loss-company-adds-a-prescription-drug-feature

4:  Summers J, Marquez Janse A, Ermyas T.  Oprah and Weight Watchers are now embracing weight loss drugs. Here's why.  Dec 18, 2023. https://www.npr.org/2023/12/18/1219710239/weightwatchers-oprah-ozempic-drugs-wegovy

5:  Fitzgerald M.  WW International extends Oprah Winfrey deal to 2025, shares rise.  CNBC  https://www.cnbc.com/2019/12/16/ww-international-extends-oprah-winfrey-deal-to-2025-shares-rise.html

 

Supplementary:

Current GLP-1 agonists - all data taken from FDA approved package inserts.

Photo Credit:

Photo by Alan Light, CC BY 2.0 <https://creativecommons.org/licenses/by/2.0>, via Wikimedia Commons