Diabetes Treatment Studies Examine GLP-1 Discontinuation and Hypoglycemia Prevention

A Cleveland Clinic study of nearly 8,000 patients who discontinued semaglutide and tirzepatide found that stopping GLP-1 medications doesn't lead to significant weight regain, mainly because many patients tend to restart the original medication or try an alternative obesity treatment. The study included patients in Ohio and Florida who were using the injectables for obesity and Type 2 diabetes, and ended up stopping the medication within three to 12 months.

The analysis showed that those treated for obesity lost an average of 8.4% of body weight before discontinuation and regained an average of 0.5% one year later. Those treated for type 2 diabetes lost an average of 4.4% of body weight before discontinuation and lost an additional 1.3% of body weight one year later. In the obesity group, 55% gained weight in the year after discontinuation, while 45% kept losing or stayed the same. In the diabetes group, 44% gained weight, while 56% kept losing or stayed the same.

The two primary issues that led to patients stopping the medication were cost or insurance coverage, and side effects. After stopping initial GLP-1 injections, 27% switched to a different medication, 20% restarted their original medication, 14% continued their obesity treatment with lifestyle modification visits with health care professionals, and less than 1% transitioned to undergoing metabolic and bariatric surgery.

A researcher with Cleveland Clinic's Center for Value-Based Care Research who led the study said real-world data show that many patients who stop semaglutide or tirzepatide restart the medication or transition to another obesity treatment, which may explain why they regain less weight than patients in randomized trials. The findings were published in the journal Diabetes, Obesity and Metabolism.

In separate research addressing hypoglycemia risk in older diabetes patients, a Kaiser Permanente clinical trial published in JAMA Network Open included 191 patients with type 2 diabetes who were at high risk for hypoglycemia, or who were at intermediate risk but had recently required emergency care for hypoglycemia and were on a sulfonylurea. The study is believed to be the first clinical trial to look at a proactive, pharmacist-led intervention to reduce diabetes medication risk in older adults.

Patients were randomized into two groups, with one group continuing usual care and the other contacted by a pharmacist who offered to discuss their diabetes treatments. The pharmacist used an evidence-based, hypoglycemia-prevention algorithm called Hypoglycemia on a Page to review current medications and offer safer treatment options. Patients spoke with the pharmacist 3 times, on average.

When the study began, 74% of the patients in both groups had treatment regimens that included medications that could increase their risk for hypoglycemia. Only about 4% had a prescription for glucagon, an injection used for the emergency treatment of severe hypoglycemia. At the end of the trial, 27 (28%) of the patients the pharmacist contacted were on a safer diabetes regimen compared with 15 (15.8%) who received usual care. In addition, 16 (16.7%) patients the pharmacist contacted received a prescription for glucagon, compared with 5 (5.3%) who received usual care.

The pharmacist made treatment regimens safer by discontinuing bolus insulin in 31 (73.8%) patients, sulfonylurea in 12 (28.6%) patients, and mixed insulin in 3 (7%) patients. Some patients discontinued more than one therapy. Most of these patients were switched to longer-acting insulin, which reduces risk for hypoglycemia.

The researchers found that 6 months into the study, none of the patients who spoke with a pharmacist experienced a hypoglycemia-related medical emergency compared with 5 (5.3%) of the patients who received usual care. Patients in both groups demonstrated a similar ability to keep their blood sugar HbA1c under 8%.