‘Watershed moment’: Obesity care in the spotlight as more drugs become available
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With reports of dramatic weight loss achieved using a new generation of diabetes drugs — one FDA approved for weight loss and another with a decision expected this fall — more adults are seeking medical therapy for obesity.
The GLP-1 receptor agonist semaglutide 1 mg (Ozempic, Novo Nordisk) was approved in 2017 to treat type 2 diabetes, and its higher-dose version, semaglutide 2.4 mg (Wegovy, Novo Nordisk), was approved in 2021 for chronic weight management for adults with obesity or overweight with at least one weight-related condition. Semaglutide is associated with weight loss of as much as 15% to 20% for some patients.
A second agent, tirzepatide (Mounjaro, Eli Lilly), a dual GIP/GLP-1 receptor agonist associated with about 15% to 20% weight loss, was approved last year to treat type 2 diabetes and is currently under FDA consideration for an indication for chronic weight management. Semaglutide and tirzepatide are currently being studied in people without diabetes and also undergoing cardiovascular outcome trials. Other GLP-1 receptor and combined agonists are in the development pipeline.
Until recently, few U.S. adults were prescribed an obesity medication. A study analyzing claims data for obesity treatment, published in 2021, found that from 2004 to 2018, only two per 100,000 individuals received a prescription. Almost 80% were written by a primary care or family medicine physician or internist; 2.7% were written by an endocrinologist and 1.1% by a cardiologist.
Of those prescriptions, 51% were for phentermine, 19% for naltrexone-bupropion (Contrave, Currax Pharmaceuticals), and 13% for liraglutide 3 mg (Saxenda, Novo Nordisk), with use of the GLP-1 receptor agonist liraglutide rising after its FDA approval in 2014. Typical duration of use for any obesity medication was about 3 months. Of patients who received a prescription, 32% had hypertension, 25% had dyslipidemia and 6% had type 2 diabetes.
Recent headlines and drug shortages seem to indicate that those prescribing trends have changed since semaglutide and tirzepatide became available.
“I truly think that this is a watershed moment in the history of obesity care, to have such effective tools to treat the disease of obesity effectively and long term,” Alpana P. Shukla, MD, MRCP, FTOS, a weight management specialist and associate professor of research in medicine and director of clinical research at the Comprehensive Weight Control Center at Weill Cornell Medicine, told Healio | Endocrine Today. “These are treatments that are not designed for people who wanted to lose 5-10 lb to get into some summer beachwear. ... The safety’s never been assessed in those people, and the prescribing needs to be responsible.”
In light of new treatment options and the growing population of physicians seeing patients for weight loss, Healio | Endocrine Today explored how different specialists approach prescribing obesity drugs.
Obesity management guidelines
The most recent practice guidelines for treating obesity were published before approval of the weight-loss indication for semaglutide — the American College of Cardiology/American Heart Association/The Obesity Society guideline in 2013, the European Association for the Study of Obesity guideline in 2015 and the American Association of Clinical Endocrinology and American College of Endocrinology guideline in 2016.
However, their general recommendations still hold, according to W. Timothy Garvey, MD, FACE, MABOM, an endocrinologist and Butterworth Professor in the department of nutrition sciences at University of Alabama at Birmingham (UAB) and director/principal investigator at the UAB Diabetes Research Center, who was lead author of the AACE guideline.
All the guidelines recommend screening adults for overweight and obesity using BMI, diagnosing and establishing treatment targets based on weight-related complications, and using pharmacotherapy and surgery for appropriate patients.
“It is difficult to recommend a hierarchy of preferred medications across the board in all patients since there have been very few head-to-head comparisons,” Garvey told Healio | Endocrine Today. “There are differences in efficacy among obesity medications in phase 3 trials although these studies enrolled different populations, different study designs and different intensities of lifestyle intervention involving placebo and active treatment subgroups. The choice of medication will depend on the amount of weight loss to predictably treat or prevent obesity complications in individual patients taking into account side effect profiles, concurrent medications and diseases, and accessibility.”
To help prescribers choose among options, AACE is developing an algorithm, expected to be published next year, to supplement its 2016 guideline, an organization representative told Healio | Endocrine Today.
A complications-centric approach
The principle behind the guidelines is to approach obesity treatment through its complications, according to Karl Nadolsky, DO, FACE, DABOM, assistant clinical professor of medicine at Michigan State University College of Human Medicine and chief of the department of endocrinology, obesity and metabolic health at Holland Hospital in Michigan.
“The basics of a complications-centric approach are that we should evaluate or grade or stage the severity of obesity not by BMI ... but by the severity of the disease, by the complications, the risk of the complications or the presence of complications, and that should dictate the intensity to which we’re treating from a behavioral perspective, pharmacotherapeutic perspective and surgical perspective,” Nadolsky, who also was an author of the AACE guideline, told Healio | Endocrine Today.
The development history of the GLP-1 receptor agonists may make them ideal agents for targeting certain obesity-related complications in addition to the obesity itself, Nadolsky said.
“Especially with severe cardiometabolic complications, like type 2 diabetes and atherosclerotic cardiovascular disease — we have cardiovascular benefit data from liraglutide and semaglutide in patients with type 2 diabetes — that definitely makes those more favorable, and they’re good for diabetes prevention for those who are at the highest risk,” Nadolsky said.
Garvey agreed.
“It’s important to realize that patients who have both obesity and diabetes lose less weight with any intervention than patients who just have obesity alone,” Garvey said. “In obesity without diabetes, we saw approximately 22% weight loss with tirzepatide and about 15% weight loss on semaglutide 2.4 mg/week. However, in patients with both obesity and diabetes, we had only seen a maximum of about 10.6% weight loss on semaglutide 2.4 mg until the recent publication of the SURMOUNT 2 study showing weight loss of about 15% in these patients.”
Garvey has recommended the term “second generation” for those obesity medications producing 15% or more weight loss on average because of the health benefits — this amount of weight loss is sufficient to treat a broad array of obesity complications, he said.
“The point is, this debate about whether we should take a weight-loss centric approach to type 2 diabetes or a glucose-centric approach to diabetes, that argument is now moot, because we have one drug that’s the best for both diseases,” Garvey said.
Cardiologists, too, are prescribing to target obesity-related complications, according to Michael J. Blaha, MD, MPH, professor of cardiology and epidemiology and director of clinical research at the Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease. Blaha treats adults with high-risk CVD, type 2 diabetes not requiring complex insulin regimens and obesity in a comprehensive cardiometabolic clinic.
“The cardiometabolic clinic concept is a place where a patient can go for comprehensive care so they don’t have to be ping-ponging between specialties,” Blaha told Healio | Endocrine Today. “We’re not doing obesity management in patients without cardiovascular disease, but it is with the goal of lowering cardiovascular risk with weight loss as a primary target. Blood pressure, diabetes, sleep apnea, potentially osteoarthritis, and then heart failure risk, we think all get better with weight loss. So, we will use weight loss as a way to get at many of those risk factors all at once in the right patient.”
The availability of the GLP-1 receptor agonists “completely shifted the noninvasive cardiologist’s focus more broadly to include weight loss and diabetes in our role,” Blaha said.
Lower-dose semaglutide and liraglutide are indicated for CV risk reduction for adults with type 2 diabetes. In August, top-line results from the SELECT trial were released showing CV risk reduction with semaglutide for adults with obesity but without diabetes.
Considerations for prescribing
Most patients seeking obesity management are still seen in primary care, where “the gist is unfortunately the same thing: ‘Eat less and exercise more’ is where a lot of it stops,” Jennifer C. Seger, MD, FOMA, ABFM, ABOM, a family medicine and obesity medicine specialist in San Antonio, told Healio | Endocrine Today.
“I’m seeing a lot of colleagues, even in my own community, who never would have written [a prescription for] phentermine, which has been on the market since 1959 ... and now all of a sudden they’re wanting to write for semaglutide while giving the patient no additional tools or information or education,” Seger said. “At this point where we are with our educational process, with the lack of obesity-specific education and training, most should be referring to obesity medicine specialists.”
For primary care providers who take on obesity management, Seger offered some steps for patient care:
To avoid stigmatizing, begin by asking a patient permission to discuss obesity, and then schedule a follow-up appointment soon to allow for a longer conversation.
Provide patient education about the physiology behind obesity, the variables that cause the body to store fat, and the fundamentals of nutrition and exercise.
Take a good history of the person’s pattern of weight gain and provide strategies for addressing individual struggles.
Consider prescribing an obesity medication.
Treating obesity can yield great health benefits for primary care, Seger said.
“If you address the weight — and I’m not saying it’s a magic wand that makes everything else go away, but I see it firsthand — you get to decrease blood pressure medicines, take people off of insulin or greatly reduce it, improve their mental health, their overall life,” Seger said.
As a weight management specialist, Shukla mostly sees patients referred from primary care, but she also has referrals from obstetricians and gynecologists for patients seeking fertility treatment and from surgeons sending patients before abdominal or transplant surgery or patients needing help to optimize weight after bariatric surgery.
When choosing among drug options, Shukla said, the first consideration is safety based on contraindications and a patient’s other medications. For example, GLP-1 receptor agonists are contraindicated for people with pancreatitis, phentermine/topiramate is contraindicated for people with kidney stones, and someone with anxiety should avoid solo phentermine, she said.
The second consideration should be comorbidities, Shukla said, with the choice of semaglutide or tirzepatide “an easy one” for someone with type 2 diabetes. Patient preference is also important for choosing among injectable or oral and daily or weekly options, as is the amount of desired weight loss.
“Prior to the availability of these highly effective medications that we have now, in our own practice, we have used a lot of the older medications,” Shukla said. “We’ve also used off-label medications because [insurance] coverage is a big issue. In fact, metformin for the patient who needs to lose 5% to 10% of their body weight remains a good, safe long-term option in combination with a low-glycemic diet.”
When choosing an obesity medication, Garvey strives for “harmonization of treatment goals” with patients involved in setting targets and clinical decision-making.
“What we’re realizing more and more with these more potent medicines, is that not every patient needs the big bomb,” Garvey said. “Patients can develop a fatigue-like or lethargy-like syndrome with this rapid, profound weight loss. ... And some don’t need 20% weight loss to get the health benefits of weight loss that they need depending upon their complication profile.”
Speaking about the headlines for semaglutide and tirzepatide, Nadolsky cautioned that prescribing drugs for weight loss for people without diagnosed obesity or weight-related comorbidities can be dangerous for patients and the health care system.
“While these medications are really safe and have great benefits, you start to have the potential side effects and risks outweigh the benefits when you [prescribe for patients who] don’t have real disease. And then also, that creates issues for people who really need these medications — supply issues and stigma and bias. We wanted to raise more awareness, and then social media and Hollywood, unfortunately, went too far to the other extreme.”
- References:
- Cornier MA. Am J Manag Care. 2022;doi:10.37765/ajmc.2022.89292.
- Garvey WT. J Clin Endocrinol Metab. 2022:doi: 10.1210/clinem/dgab848.
- Garvey WT, et al. Lancet. 2023:doi:10.1016/S0140-6736(23)01200-X.
- Novo Nordisk A/S: Semaglutide 2.4 mg reduces the risk of major adverse cardiovascular events by 20% in adults with overweight or obesity in the SELECT trial. Available at: www.novonordisk.com/news-and-media/news-and-ir-materials/news-details.html?id=166301. Published: Aug. 8, 2023. Accessed: Aug. 27, 2023.
- Suissa K, et al. Diabetes Obes Metab. 2021;doi:10.1111/dom.14367.
- For more information:
- Michael J. Blaha, MD, MPH, can be reached at mblaha1@jhmi.edu; X (Twitter): @MichaelJBlaha.
- W. Timothy Garvey, MD, MACE, MABOM, can be reached at ude.bau@tyevrag.
- Karl Nadolsky, DO, FACE, DABOM, can be reached at drkarl@leanerliving.com; X (Twitter): @DrKarlNadolsky.
- Jennifer C. Seger, MD, FOMA, ABFM, ABOM, can be reached at jcseger@gmail.com.
- Alpana P. Shukla, MD, MRCP, FTOS, can be reached at aps2004@med.cornell.edu; X (Twitter): @alpanashuklamd.
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