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Revolutionizing obesity treatment: The multifaceted benefits and risks of GLP-1 drugs

By Jeff Levin-Scherz, MD, MBA | August 13, 2025

GLP-1 drugs can help with obesity by aiding 15-20% weight loss and improving health outcomes. But they can have adverse effects, which highlights the need for careful consideration and monitoring.

Glucagon-like peptide (GLP-1) medications are highly effective at helping patients lose 15% or more of their weight. But they are expensive, generally costing employers $7,500-$9,000 annually, even after rebates and discounts. Some employer plans find that these two medications, semaglutide (Wegovy) and tirzepatide (Zepbound), represent as much as 10% of their total outpatient pharmacy spending, and an outsized portion of pharmacy inflation. These drugs are available directly from pharmaceutical companies for about $6,000 per year for those without insurance coverage.

GLP-1 drugs have been used for about two decades to treat diabetes. Their safety and side effect profiles are well understood.

The Food and Drug Administration (FDA) has approved Wegovy (semaglutide) and Zepbound (tirzepatide) to treat those with obesity or those who are overweight with metabolic complications (such as heart disease, hypertension or hypercholesterolemia). An older drug, Saxenda (liraglutide), was approved in 2014 but requires daily injections and results in only ~5% average weight loss. About 42% of the adult population could be eligible for these medications. Most long-term studies of GLP-1 drugs are in people with diabetes, as semaglutide was only approved for obesity in June 2021, and tirzepatide was only approved for obesity in November 2023.

The diabetes versions of the obesity-labeled GLP-1 drugs are the same drug. Maximum doses available for semaglutide for diabetes (Ozempic) are lower than those labeled for obesity (Wegovy). Doses available for Zepbound and Mounjaro are identical. Drugs labeled for diabetes are generally about 20% less expensive than drugs labeled for obesity.

Clinical benefits of GLP-1 drugs

  1. 01

    Weight loss

    These drugs are highly effective at helping patients achieve a medically desirable weight. Semaglutide generally leads to 10–15% weight loss, and tirzepatide generally leads to 15–20% weight loss. Weight reduction has been associated with improvements in mental health and improved employment prospects. Here’s a recent Reuters article on the impact of weight loss on obese adolescents.

  2. 02

    Heart disease

    A randomized trial published in the New England Journal of Medicine in 2023 showed that the risk of major adverse cardiovascular events was 20% lower in those with previous heart disease and without diabetes who were treated with semaglutide compared to those treated with placebo. The trial was discontinued early based on positive results. Wegovy is approved for this indication.

Complications associated with weight loss in general and not specific to GLP-1 use

  1. 04

    Cholecystitis (gallbladder inflammation)

    Many people who lose a substantial amount of weight (through GLP-1s, bariatric surgery, or diet) have gallbladder attacks.

  2. 05

    Loss of muscle mass

    Those who lose substantial amounts of weight lose both fat and lean body mass. Loss of muscle doesn't appear to be worse with GLP-1 use than with other weight loss mechanisms. Exercise and diet can reduce muscle loss, and the clinical implications of loss of lean body mass aren't clear.

Complications that aren't confirmed to be due to GLP-1 use

  1. 06

    Pancreatitis

    There are reports of pancreatic inflammation with GLP-1 medications, although causality isn't confirmed, and this hasn't been observed in large observational studies. Clinical trials generally excluded those with a history of acute pancreatitis. At least one large claims review showed lower rates of pancreatitis with the use of GLP-1 drugs than with other drugs used to treat diabetes.

  2. 07

    Thyroid cancer

    The GLP-1 drugs have an FDA “black box” warning of the risk of a rare type of thyroid cancer. But there's no convincing observational evidence that this risk is being seen in clinical use. The warning was based on rodent experimental evidence.

Complications not likely to be due to GLP-1 use

  1. 08

    Depression and suicidality

    Early reports suggested that GLP-1 medications might increase depression and suicidal ideation. More recent population studies show a statistically significant decrease in suicidal ideation and suicides in those on GLP-1 medications. Here are studies (1) (2) that show lower rates of depression and suicide in those treated with GLP-1 medications.

  2. 09

    Cancer

    Observational studies (see above) show that GLP-1 use is associated with a decrease in cancer incidence. Given that this drug class has been used widely for two decades, it's unlikely that these drugs will be found to increase the risk of future cancers.

GLP-1 drugs clearly offer substantial health benefits for members with obesity and can prevent serious future disease. However, the cost of the drugs is far higher than savings from preventing these bad outcomes. Demand for these drugs is high and could increase when oral versions become available. The high price of these drugs places coverage out of reach for some employers. Some pharmacy benefit managers say they have achieved better net prices by restricting their formulary to either Zepbound (tirzepatide) or Wegovy (semaglutide). Future new market entrants could help lower the acquisition price for these medications.

FAQ – Frequently asked questions

Glucagon-like peptides:

  • Glucagon-like: Because GLP-1 looks like another hormone called glucagon
  • Peptide: A smaller type of hormone that’s made out of amino acids
  • 1: Just a naming convention; there’s a GLP-2 hormone but there is no GLP-3
  • Agonist: This term usually means a drug activates a process in the body

GLP-1 drugs like semaglutide (Wegovy and Ozempic) and tirzepatide (Zepbound and Mounjaro) were developed to treat type 2 diabetes, but they’ve gained media attention in the past couple of years for their ability to help people lose weight. These drugs are expensive and mostly given as a self-injection. The drugs to treat obesity and to treat diabetes are the same, although the obesity medications are more expensive and sometimes come in higher doses.

In addition to weight loss and better diabetes control, these drugs have been shown to decrease onset of diabetes in those with prediabetes, decrease progression to kidney failure, and decrease heart attacks in those at high risk. They are also approved for obstructive sleep apnea (Zepbound), metabolic liver disease (MASH, Wegovy), and heart disease prevention (Wegovy). Studies have shown lower risk of obesity-related cancers, too.

Many people treated with these medications have gastrointestinal side effects like nausea and constipation, and these often abate over time. Substantial weight loss from surgery, diet or these drugs leads to loss of lean body mass, and loss of fat tissue can accentuate facial wrinkles.
  • Ozempic
  • Rybelsus
  • Saxenda
  • Trulicity
  • Victoza
  • Wegovy
  • Zepbound

Author

Jeff Levin-Scherz
Jeff Levin-Scherz, MD, MBA
Population Health Leader

Jeff is an internal medicine physician and has led WTW’s clinical response to COVID-19 and other health-related topics. He has served in leadership roles in provider organizations and a health plan and is an Assistant Professor at Harvard Chan School of Public Health.

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