Obesity experts offered practice pearls on managing obesity with semaglutide and tirzepatide at a recent conference convened by the Endocrine Society.1 Below are highlights on how these anti-obesity medications work, side effects, drug shortages, and barriers to uptake applicable to primary care providers and obesity specialists.

1. Semaglutide and tirzepatide work by suppressing the body’s compensatory mechanisms during weight loss

  • Only one-third of patients with obesity can achieve weight loss of 5% or more with intensive behavioral changes in diet and exercise alone. Why? “We are shaped by evolution to defend a certain fat mass or body weight set point,” said Michael Weintraub, MD, of NYU Langone Health and NYU Grossman School of Medicine in New York City. “When we lose weight, our body doesn’t know we lost that weight intentionally. Our body physiology pushes back to regain that weight through various mechanisms such as increasing appetite and decreasing energy expenditure.”
  • Obesity medications used long-term typically act centrally on appetite centers of the brain to decrease food cravings and intake so that weight loss is sustainable, Dr Weintraub explained.

2. Semaglutide and tirzepatide need to be taken lifelong to be effective in obesity

  • “Just like with medications for hypertension and diabetes, we know that you need to continue taking obesity medications to have an effect,” said Ro Pereira, MD, of Denver Health Medical Center and the University of Colorado in Denver, Colo.

3. Patients with gastrointestinal (GI) side effects when starting semaglutide and tirzepatide tend to have the best treatment response

  • Anecdotal evidence suggests that the best responders to these agents are those with GI symptoms upfront, said Amy Rothberg, MD, of the University of Michigan in Ann Arbor, Mich.
  • Common side effects including nausea, diarrhea, and constipation are mitigated over time and can be lessened with slow dose escalation, Dr Rothberg said.
  • Serious adverse events are rare and may include cholelithiasis, pancreatitis, and hypoglycemia.

4. Patients are more willing to start an injectable obesity medication than insulin injections

  • “Interestingly, people are much more willing to inject the medication that is going to help them lose weight and improve their blood sugar than insulin,” Dr Pereira said.
  • Patients associated insulin with multiple daily injections and weight gain, whereas many of these newer obesity medications are available as weekly injections, she said.  

5. Drug shortages, advertising to consumers, cost, insurance coverage, and stigma are barriers to uptake of newer antiobesity medications

  • Drug shortages affected patient access to semaglutide beginning in October 2022, the panelists reported. “National shortages were related to a constellation of factors: continued direct-to-consumer marketing increasing demand, manufacturing shortfall, and prescribing for less than appropriate purposes,” Dr Rothberg said.  
  • Dr Pereira said that many of her patients are still experiencing issues accessing semaglutide because of supply issues. In some patients, a higher dose of semaglutide was prescribed but that dose was not available and patients had already run out of their previous lower dose and were left with no medication. “We have had a lot of interactions trying to get patients back on the previous dose,” she said.
  • “Although we know that the newer obesity medications improve blood glucose, heart function, and help with weight loss, a lot of times they still are not covered by insurance plans or people have very high copays and are not able to afford them,” Dr Pereira said.
  • “Many patients who are unable to afford the newer antiobesity agents are also the ones that are most vulnerable to the consequences of obesity,” Dr Weintraub said. “Continued lack of insurance coverage only will widen those health disparities that we have in our country. Hopefully, this will be corrected in the future.”
  • Stigma related to obesity and not considering it a disease rather than a lifestyle choice is linked to skepticism among the public on the use of effective treatments for obesity, Dr Rothberg said.

Obesity Medication Fast Facts1,2

• Semaglutide is a GLP-1 agonist approved for the management of obesity under the brand name Wegovy with an average weight loss of approximately 15% in the STEP-1 trial1
• It is also approved at a lower dose as a diabetes treatment under the brand name Ozempic
• Tirzepatide is a dual GLP-1 agonist and GIP receptor agonist undergoing FDA review for the treatment of obesity with an average weight loss of approximately 21% at the highest dose used in the SURMOUNT-1 trial2
• It is currently approved for the treatment of diabetes
• Other medications approved for long-term use in the management of obesity include naltrexone-bupropion, orlistat, and phentermine-topiramate
GLP-1, glucagon-like peptide-1; GIP, glucose-dependent insulinotropic polypeptide; GIP, receptor agonist


1. Virtual Science Writers Conference will explore impact of antiobesity medications. News release. Endocrine Society: February 7, 2023. https://www.youtube.com/watch?v=RCXKPk1xVck

2. Aronne L, Jastreboff A, Le Roux C, et al. Tirzepatide reduces body weight across BMI categories: a SURMOUNT-1 pre-specified analysis. Obesity. November 21, 2022. Oral abstract 110. https://doi.org/10.1002/oby.23625

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3. Wilding JPH, Batterham RL, Calanna S, et al; STEP 1 Study Group. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021;384(11):989-1002. doi:10.1056/NEJMoa2032183