A large real-world study shows that patients who stop popular GLP-1–based weight-loss drugs often return to treatment or try alternative therapies, helping explain why average weight regain after discontinuation may be smaller than expected.
Study: Obesity Treatments and Weight Changes in Clinical Practice After Discontinuation of Semaglutide or Tirzepatide. Image credit: KaterynaBorodina/Shutterstock.com
Obesity treatment has been revolutionized by the introduction of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) like semaglutide, and dual GLP-1 RA/glucose-dependent insulinotropic polypeptide [GIP] receptor agonists like tirzepatide. However, a study published in Diabetes, Obesity and Metabolism found that many patients who discontinue these medications either restart treatment or switch to other options within a year.
Rising popularity of GLP-1 therapies
Obesity affects about 40 % of American adults. It increases the risk of type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver, and obstructive sleep apnea 3-11-fold. The steep weight loss and significant cardiovascular and metabolic benefits associated with drugs like semaglutide and tirzepatide underlie their rapid rise in popularity.
According to another study, one in five American women between 50 and 64 years of age reported having tried one or more of these medications. Even so, prior studies suggest that up to 65 % of patients discontinue them within a year, and discontinuation has been associated with weight regain and reduced cardiometabolic benefits.
Examining patient outcomes after GLP-1 discontinuation
The study used a retrospective cohort design and data from a large healthcare system in Ohio and Florida. All participants were overweight or obese and were on injectable semaglutide or tirzepatide for either obesity or T2DM. The study focused on patients who discontinued the medication within 3–12 months of initiation. The researchers examined treatment patterns and weight changes following discontinuation.
Many patients restart or switch therapies after discontinuation
The study included 7,938 patients who had started injectable semaglutide or tirzepatide. Most participants were White (75 %) and female (64 %), with a mean age of 55.7 years. At baseline, the average body weight was 113 kg, and the mean body mass index (BMI) was 39.5. Most patients were covered by private insurance.
Semaglutide was the most commonly prescribed medication. Overall, 46 % of patients initiated semaglutide for T2DM and 32 % for obesity. Tirzepatide was used less frequently, with about 12 % of patients starting it for T2DM and 10 % for obesity.
Among those prescribed these medications for obesity, many patients discontinued treatment before reaching what the authors describe as adequate therapeutic doses. The reasons for this pattern remain unclear and warrant further investigation. The researchers note that pricing structures may play a role, as lower doses are sometimes offered at reduced prices through self-pay channels. Future studies should explore whether such pricing models contribute to deviations from recommended dose-escalation schedules.
Post-discontinuation, 19.6 % restarted the original medication, while 35 % adopted another option: alternative medication (27.4 %), healthcare visit for lifestyle modification (13.7 %), and metabolic and bariatric surgery (0.6 %). These categories may not be exclusive.
Among patients who restarted their medications, 14 % received it for obesity and 24 % for T2DM. This may be because insurance coverage of the use of these agents is broader in T2DM than for obesity. The mean time to restarting was 177 days longer in obesity than in T2DM. Among alternative medications, approximately the same proportion (<18 %) switched between tirzepatide and semaglutide either way. Other medications included phentermine, topiramate, and bupropion.
Lifestyle-related visits included educational single or shared visits with healthcare professionals focused on nutrition, exercise, and weight management (in isolation or as part of diabetes management).
On average, patients treated for obesity lost 8.4 % of their original body weight while on the medication, compared with a 4.4 % reduction among those treated for T2DM. One year after discontinuation, patients treated for obesity had gained 0.5 % of their baseline weight, whereas those treated for T2DM had lost a further 1.3 %.
However, these averages masked substantial variation between individuals. Some patients regained significant weight after stopping treatment, while others maintained their weight loss or continued to lose weight. Overall, 55 % of patients treated for obesity experienced weight gain after discontinuation, compared with 44 % of those treated for T2DM. These estimates were based on patients with available follow-up weight measurements, representing a subset of the full study population.
Further research is required to compare various alternative treatments for post-GLP-1 RA or dual receptor agonist patients.
Strengths and limitations
The authors describe this as the first study to examine obesity treatment uptake in detail, combined with the direction of weight change during and after discontinuation. It was based on a large sample, robust data sources, and a diverse study population. The analysis also drew on linked electronic health record and prescription-dispensing data, and included obesity treatment at both specialist and generalist care settings.
Despite these strengths, the study has several limitations. The sample was drawn from a single healthcare system across two southern states, which may limit the generalizability of the findings. In addition, all patients received both their initial and follow-up care within the same centers. Drug shortages during the study period may also have influenced treatment patterns. The analysis could be affected by residual confounding from unsupervised lifestyle modifications, and importantly, the reasons for treatment discontinuation were not recorded.
Restarting or switching therapies common after GLP-1 discontinuation
Among patients who discontinued tirzepatide or semaglutide within the first year of treatment, many restarted the original medication or switched to another treatment. The weight change at one year post-discontinuation was small, but depended heavily on the individual and may partly reflect the fact that many patients resumed or transitioned to other weight-management therapies rather than remaining untreated.
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