GLP-1 Weight Loss Drugs: Many Patients Restart or Switch Therapies After Stopping

A recent study indicates that many individuals who discontinue glucagon-like peptide-1 receptor agonist (GLP-1 RA) medications for weight loss, such as semaglutide and tirzepatide, often resume treatment or explore alternative therapies, suggesting that initial weight regain concerns following discontinuation may be less pronounced than previously thought.

Rising Popularity of GLP-1 Therapies

Obesity affects approximately 40% of American adults and significantly increases the risk of associated health issues like type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease, and obstructive sleep apnea. Drugs like semaglutide and tirzepatide have gained rapid popularity due to their substantial weight loss benefits and positive impacts on cardiovascular and metabolic health.

Recent data suggests that around one in five American women aged 50 to 64 have tried these medications. Though, prior research indicated that up to 65% of patients discontinue them within a year, potentially leading to weight regain and a reduction in cardiometabolic benefits.

Study Examines Patient Outcomes After Discontinuation

A retrospective cohort study analyzed data from a large healthcare system in Ohio and Florida. The study focused on overweight or obese patients who had been using injectable semaglutide or tirzepatide for either obesity or T2DM and had discontinued the medication within 3 to 12 months of starting it. Researchers examined treatment patterns and weight changes following discontinuation.

Restarting or Switching Therapies is Common

The study included 7,938 patients, with a majority being White (75%) and female (64%), with an average age of 55.7 years. The average baseline body weight was 113 kg, and the mean body mass index (BMI) was 39.5. Most patients had private insurance.

Semaglutide was the most frequently prescribed medication. Approximately 46% of patients initiated semaglutide for T2DM and 32% for obesity, while tirzepatide was used less often, with about 12% starting it for T2DM and 10% for obesity.

Notably, many patients prescribed these medications for obesity discontinued treatment before reaching adequate therapeutic doses. The reasons for this are currently unclear and require further investigation. Pricing structures may play a role, as lower doses are sometimes available at reduced prices.

Following discontinuation, 19.6% of patients restarted their original medication, while 35% adopted another option, including alternative medication (27.4%), healthcare visits for lifestyle modification (13.7%), and metabolic and bariatric surgery (0.6%).

Among those who restarted their medications, 14% were treated for obesity and 24% for T2DM. This difference may be attributed to broader insurance coverage for these agents in the treatment of T2DM compared to obesity. The average time to restarting was 177 days longer for obesity than for T2DM. Approximately 18% switched between tirzepatide and semaglutide in either direction. Other alternative medications included phentermine, topiramate, and bupropion.

Lifestyle-related visits encompassed educational sessions with healthcare professionals focused on nutrition, exercise, and weight management, either independently or as part of diabetes management.

Weight Changes After Discontinuation

Patients treated for obesity experienced an average weight loss of 8.4% while on the medication, compared to a 4.4% reduction in those treated for T2DM. One year after discontinuation, patients treated for obesity had gained 0.5% of their baseline weight, while those treated for T2DM experienced a further 1.3% weight loss.

However, these averages masked significant individual variation. Some patients regained substantial weight after stopping treatment, while others maintained their weight loss or continued to lose weight. 55% of patients treated for obesity experienced weight gain after discontinuation, compared to 44% of those treated for T2DM.

Future Research

Further research is needed to compare the effectiveness of various alternative treatments for patients who discontinue GLP-1 RAs or dual receptor agonists.

Study Strengths and Limitations

The authors highlight this as the first study to comprehensively examine obesity treatment uptake alongside weight changes during and after discontinuation. The study benefited from a large sample size, robust data sources, and a diverse population. The analysis combined electronic health record and prescription data from both specialist and generalist care settings.

However, the study has limitations. The sample was drawn from a single healthcare system in two southern states, potentially limiting the generalizability of the findings. All patients received care within the same centers, and drug shortages during the study period may have influenced treatment patterns. The analysis may also be affected by uncontrolled lifestyle modifications, and the reasons for treatment discontinuation were not recorded.

the study demonstrates that among patients who discontinued tirzepatide or semaglutide within the first year, many either restarted the original medication or switched to another treatment. The weight change at one year post-discontinuation was relatively small, potentially reflecting the fact that many patients continued some form of weight-management therapy.