The Impact of Obesity by Michele Brezinski, MD
Copyright 2026 Managed Medical Review Organization, Inc. All rights reserved.
This white paper is informed by findings from an inter-rater reliability analysis conducted as part of the underlying research.
The impact of the global obesity epidemic cannot be overstated. Leaders in the public health field call it one of the most significant challenges of the 21st century. Here in the United States, we have one of the highest obesity rates in the world. In 2022, the adult obesity prevalence had risen to 42.5% - up from just 19.3% in 1990, and the percentage of adults over the age of 25 who are overweight or obese is nearly 75%.
Despite the massive 221 billion dollar weight management industry, the vast majority of adults who are overweight or obese fail to lose weight and keep it off long-term. What was once thought of as a willpower problem or an inherited predisposition is now accepted to have significant biochemical components.
The medical impact of obesity extends far beyond diabetes and sleep apnea. Excess body weight and the resultant impact upon inflammation, glucose processing, and internal stressors play a role in major health conditions affecting every part of the body. According to the IARC, being obese is linked to increased rates of 13 different cancers, with research out of Europe identifying another 18 types of cancer likely to be impacted. Obesity is one of the leading causes of advanced liver disease, and is also linked to Alzheimer’s disease, arthritis, infertility, chronic back pain, and numerous other conditions.
Given the far-reaching impact of obesity and its rapidly increasing prevalence, the pharmaceutical industry has been investigating obesity medications for decades. Weight loss medications are not a new idea, but the industry has been fraught with issues. Phentermine was approved by the FDA in 1959; however, in the early 1990s it was combined with fenfluramine (approved in 1973) to make Fen-phen. Use of the combination was short-lived, however, as it was pulled from the market after it was shown to cause damage to heart valves and pulmonary hypertension. Then came Orlistat, now over the counter, which is frequently tried but rarely continued long-term due to the unpleasant nature of the GI side effects. Numerous other agents have been transiently approved and then pulled from the market months or years later when dangerous side effects were recognized.
The Advent of GLP-1 Medications
It was into this backdrop of limited treatment options, expanding waistlines, and rising type II diabetes rates that GLP-1 receptor agonist drugs (typically referred to as simply GLP-1s) arrived on the market. Most people are not aware that GLP-1 medications have been around for more than 20 years. Exenatide (Byetta) was first approved by the FDA in 2005 for the treatment of type II diabetes. The medication had a solid 0.81% decrease in A1c levels in clinical studies, but the excitement came when the research yielded evidence of modest weight loss (1- 2 kg). At that time, most diabetes medications aside from metformin were weight-neutral at best, with many leading to weight gain. This weight gain led to worsening glycemic control in a vicious cycle that health professionals were helpless to stop. Because the twice-daily injections represented a barrier to use for many patients, a once-weekly formulation, Bydureon, was eventually developed. This medication not only had even better A1c reduction (1.3-1.9%) but demonstrated sustained benefits in A1c levels and body weight for 5-6 years.
Following Byetta’s initial success, liraglutide (Victoza) was released in 2010. When high-dose liraglutide (Saxenda) was released in December 2014, it became the first GLP-1 medication to be approved for obesity treatment after research studies demonstrated that over 25% of participants lost more than 10% of their body weight and over half lost at least 5%. These initial GLP-1 medications carried high rates of gastrointestinal side effects, however, and also required frequent injections.
With the more recent development of semaglutide and other subsequent GLP-1 agents with more prolonged duration of action and more favorable side effect profiles, these older medications have largely been supplanted by the newer drugs.
Who Benefits from GLP-1 Treatment?
The original STEP trials for semaglutide for weight loss (STEP 1, 3, and 4) required a BMI of at least 30 (obesity) or at least 27 with a weight-related comorbid medical condition. Eligible conditions included high blood pressure, abnormal cholesterol, obstructive sleep apnea (OSA), or cardiovascular disease. Participants were also required to have at least one self-reported unsuccessful dietary effort at weight loss. Individuals with previous obesity surgery, weight-loss devices, or use of any weight-loss medications within 90 days were excluded – as were diabetics, as they were studied in the STEP 2 trial. The FDA guidelines for Wegovy are based on the STEP trial criteria.
The key thing to note about the STEP trials is that the FDA indication for “use in combination with a reduced calorie diet and increased physical activity” comes from these studies. STEP 1, 2, and 4 required concomitant lifestyle modification consisting of a 500kcal/day deficit and 150 min/wk of exercise. The inclusion of lifestyle modification was driven by the FDA draft guidance for companies developing obesity medications, which mandates that all phase three clinical trials incorporate a lifestyle modification (diet and exercise) program as well. Because of this mandate, it is unquantified how effective GLP-1 medications are in the absence of concomitant lifestyle modification.
Although there is no direct research, it is notable that the STEP 3 study required intensive behavioral therapy consisting of eight weeks of low-calorie meal replacement followed by a reduced-calorie diet plus 200 min/wk of exercise. This trial also included a total of 30 dietitian visits. Despite this, the total weight loss numbers were only modestly better than the STEP 1 trial – 16% compared with 14.9%. In fact, when researchers accounted for the placebo group, the semaglutide-attributable weight loss was better in STEP 1 (12.4% versus 10.3%), indicating that the patients who benefitted the most from the intensive lifestyle intervention were part of the placebo group.
GLP-1s in Clinical Practice
Following the FDA approval of Wegovy for weight loss in individuals who are obese or overweight with certain weight-related medical conditions, patients began to seek out treatment with these agents. The change was slow at first. Patients who had tried one intervention after the other for years were wary of another new drug. Many discovered that their health plan did not cover treatment and found the out-of-pocket cost prohibitive (around $16,000 in the US). But as advertising campaigns featuring sports professionals and media personalities began to appear on social media and traditional news outlets, the barriers to care and social stigma around taking medication for obesity began to lessen.
Unlike many health conditions, obesity is not silent in its early stages. It confronts patients with its presence every day when they try to zip up a favorite pair of pants or squeeze into a seat in a crowded conference room. It is perhaps no coincidence that the overwhelming majority of prescriptions for GLP-1 obesity medications come from the health professionals who know the patient best - primary care physicians (family medicine and internal medicine) and advanced practice providers (NPs and PAs) in primary care.
Yet these physicians face numerous challenges in providing care. Obesity is often only one of many issues to be addressed at a 15-minute follow-up visit. The importance of discussing the need for certain dietary modifications while on GLP-1 treatment means that detailed discussion and documentation of lifestyle interventions before and during treatment takes a back seat, as the physician knows the patient and is familiar with their history of attempted weight loss. This becomes a problem when documentation is later reviewed to determine health plan coverage for the medication.
Evolving Health Insurance Coverage
When Wegovy (semaglutide labelled for weight loss) was approved for weight loss in 2021, commercial insurance coverage for the medication was poor – only about 14% of employer-sponsored plans covered the medication for weight loss. This was in stark contrast to the coverage rate of Ozempic (semaglutide labelled for diabetes use), which was around 75%. In both cases, however, there were stringent criteria that patients had to meet to receive the medication. As utilization rates climbed and weight loss clinics popped up on every corner of the internet, these criteria have only increased.
The increase in demand for GLP-1 medications, coupled with the increasing complexity of coverage requirements, has led to an increase in cases being referred to IROs for clinical review. Cases concerning whether weight-loss medications are a covered benefit remain straightforward; however, cases involving formulary and medical necessity requirements yield complex algorithms of “if this, then that.”
Despite the length of the criteria and the need to pay particular attention to the words “AND” and “OR”, the decision-making process in most cases continues to be centered on the concepts of BMI, dietary modification, and exercise. The first pillar defines whether or not the patient is overweight or obese, and the latter two remain the cornerstone of medical management of obesity.
Understanding Obesity Treatment Guidelines
The reason IRO reviewers continue to focus on documentation surrounding a reduced calorie diet and physical activity is that these things remain the cornerstone of professional treatment algorithms for obesity. Whether it’s the American Association of Clinical Endocrinology, the Obesity Society, USPSTF, or any other professional society guidelines, diet and exercise have always come first. They form the base of the pyramid after which all other treatments are considered.
The reason for this goes beyond cost, risk-benefit ratios, and the old prejudices about willpower and effort. Simply put, lifestyle choices are the major modifiable cause of obesity. The standard American diet and physical inactivity have driven the obesity epidemic. And according to clinical research, this is where change needs to occur for patients to achieve successful long-term weight-loss maintenance.
Therefore, physician experts evaluating claims for medical necessity of GLP-1 medications continue to place emphasis on evidence supporting pursuit of lifestyle modification. The difference, however, is that a physician working in conjunction with an IRO can review the provided information about diet and exercise in light of any comorbid conditions that the patient may have. Medical necessity is determined not just on BMI and reported failed attempts at weight loss, but also on a patient’s ability to be active due to an MS diagnosis, or their dietary constraints due to eosinophilic esophagitis and irritable bowel syndrome.
More Than Obesity
The GLP-1 weight loss market began to change in March 2024 with publication of the results of multiple new clinical research studies. The SELECT trial data demonstrated improved cardiovascular outcomes with semaglutide in patients without diabetes. Prior studies in 2016, LEADER (liraglutide) and SUSTAIN-6 (semaglutide), had shown cardiovascular risk reduction in patients with diabetes. After semaglutide was approved for weight loss in patients without diabetes, researchers wondered if the same decreased risk of heart attack would be seen in non-diabetic obese patients. And it was. The SELECT trial demonstrated that semaglutide had meaningful benefits in those with cardiovascular disease even in the absence of diabetes. The key findings included a 28% reduction in nonfatal heart attack and a 19% reduction in all-cause mortality. But the most impressive note was that these findings were independent of baseline A1c levels (whether the patient was pre-diabetic or insulin resistant) and independent of magnitude of weight loss (though participants did average 10% weight loss over four years).
The advent of clinical endpoint studies showing benefits that far exceeded weight loss has made semaglutide and tirzepatide unique in comparison with older weight-loss medications. With an increasing number of studies showing benefit for a wide variety of conditions, the concept of medical necessity has taken on a new level of complexity. What used to be an analysis of whether the patient has sufficiently shown that they cannot lose weight through lifestyle measures and other anti-obesity medications is now becoming an analysis of individualized risk and complex comorbidities.
Current Issues Surrounding GLP-1 Treatment
Financial implications aside, it’s easy to think that all 75% of the US population who are obese or overweight should take GLP-1 medications. After all, then nobody would be overweight, and all of our health problems would be solved – right? Unfortunately, it’s not that simple.
GLP-1 medications, like all medications, have potential risks and side effects of treatment. These are real problems that occurred often enough during clinical research to be directly attributed to use of the medication itself. For GLP-1 medications, these are primarily gastrointestinal issues – from mild nausea to vomiting to severe slowing of gut motility and everything in between. They can cause gallstones and pancreatitis, which can require hospitalization, and can also affect vision, heart rate, and lead to neurologic symptoms. And even if tolerated, the medications do not provide the desired level of weight loss for everyone who takes them.
Then there are the unanswered questions. What happens once patients have lost enough weight that their BMI is normal or their weight loss has plateaued? At this stage, insurance coverage becomes an even greater challenge. Although the FDA indications include weight loss maintenance, there are no longitudinal studies of patients on medication for five or ten years out. The longest clinical research study was SELECT, which terminated after four years of treatment and focused on cardiovascular outcomes as opposed to weight management (with 10.2% weight loss seen). So truly long-term safety is unknown. While early studies such as the STEP 1 extension are suggesting weight regain in a significant percentage who stop treatment, nobody really knows yet what the statistics will be. Nobody knows if microdosing works and to what extent. Nobody knows if there’s a way to tell who needs treatment forever and who doesn’t.
Role of the Independent Review Organization
Although GLP-1 medications shouldn’t be taken by everyone, the current utilization is increasing and represents a small but growing percentage of potentially eligible patients. As additional layers of requirements have been placed surrounding treatment, IROs have seen progressively higher volumes of cases surrounding determination of whether or not treatment is medically necessary. Given the impact of obesity to change an individual’s health trajectory, there is increased pressure on reviewing clinicians to produce accurate, well-supported determinations.
This starts with the process of selecting the right physician to review the claim. Most of the time, this means choosing a primary care physician with clinical experience using GLP-1 medications. While cardiologists and endocrinologists do write for these medications – and should do so based on cardiovascular outcome trial data – they comprise a small percentage of the total prescriptions. The vast majority of the care of patients using GLP-1 medications is overseen by primary care physicians. At MMRO, our coverage reviews are specialty-matched with the attending (prescribing) physician, and we have a large panel of experienced physicians able to look at all facets of these cases.
The capacity to look at more than one issue is crucial as pharmaceutical management of obesity is complex, taking into account not just absolute body weight and BMI, but the interplay between numerous comorbid conditions and complex risk factors. These things impact a patient’s ability to lose weight, keep it off, comply with lifestyle modification, tolerate treatment, and undergo treatment without undue risk of adverse outcomes.
Also crucial to producing a clinically validated outcome is the ability to incorporate the ever-growing database of post-approval information and experience. Physicians have taken the baseline trial data and added to it a wealth of clinical experiences and ongoing research data. Leaders in the field have updated professional guidelines to reflect a constantly evolving standard of care in the management of obesity and related conditions.
At MMRO, we recognize this rapid evolution of clinical research and standards of care increases the risk of both prescribing and reviewing physicians not being up to date regarding best practices. We work diligently to ensure that the standards applied are both current and consistent, regardless of which physician reviews the claim.
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