The high cost of semaglutide and other GLP-1 drugs is likely behind many of the discontinuations.
Roughly one out of every two people who start taking semaglutide (Wegovy; Novo Nordisk) to lose weight will stop taking the medication within a year, according to a large population-based study out of Denmark.
The discontinuation rate rose from 18% at 3 months to 52% at 12 months, Reimar Thomsen, MD, PhD (Aarhus University Hospital, Denmark), reported this week at the annual meeting of the European Association for the Study of Diabetes (EASD) in Vienna, Austria.
Younger people, men, and those with lower incomes, higher comorbidity burdens, and past use of psychiatric and GI medications were more likely to go off treatment than others.
“But there was no really clear subgroup that did not have a high stopping rate,” Thomsen told TCTMD. “There were a lot of factors that were kind of modest predictors, but not strong predictors. That makes it a little bit difficult to predict who will stop.”
The findings are consistent with prior research, primarily from the United States, showing that a large proportion of patients initiating treatment with a glucagon-like peptide-1 (GLP-1) receptor agonist like semaglutide for weight loss stop taking their medications, often leading to a rebound in body weight. Cost and the well-known GI side effects of the drugs are believed to be the leading reasons for discontinuation.
Thomsen and his colleagues wanted to explore the situation in Denmark, a country that has a more socialized healthcare system than the US, but still requires people to pay out of pocket for GLP-1 receptor agonists when used for weight loss in most cases; the drugs are reimbursed when used to treat diabetes.
“We believe that financial constraints could definitely play a role here also in Denmark,” Thomsen said.
Need for Better Counseling
The study included the first 77,310 people (median age 50 years; 71% women) who did not have diabetes and started taking semaglutide for weight loss in Denmark, with data coming from nationwide registries.
During the study period, men were significantly more likely than women to stop taking semaglutide (adjusted risk ratio [RR] 1.12; 95% CI 1.11-1.14). In addition, compared with individuals ages 45 to 59 years, the rate of discontinuation was higher for those ages 18 to 29 years (RR 1.48; 95% CI 1.45-1.51) and 30 to 44 years (RR 1.24; 95% CI 1.22-1.26). Those older than 59 years also had greater risks of stopping treatment, but the magnitude of the relationships was smaller than for their younger counterparts.
Individuals making 300,000 Danish Krones (about $48,000 in US dollars) per year were more likely to stop treatment than their higher-earning peers, as were patients taking psychiatric, GI, and other anti-obesity medications.
A variety of comorbidities, including HbA1c-defined prediabetes, hypertension, dyslipidemia, metabolic syndrome, polycystic ovary syndrome, CVD, asthma, sleep apnea, knee arthrosis, and thyroid diseases, as well as overall comorbidity burden, were also associated with higher rates of discontinuation, with RRs ranging from 1.03 to 1.11.
The only factor tied to a lower risk of dropping treatment was bariatric surgery (RR 0.85; 95% CI 0.81-0.89).
An additional case-control analysis focused on events that occurred after the initiation of semaglutide, showing that discontinuation was associated with starting psychiatric or GI medications, getting pregnant, undergoing bariatric surgery, or developing thyroid disease, biliary/pancreatic cancer, or any cancer.
“The key takeaway is that stopping rates are simply very high—too high in my mind.” Reimar Thomsen
He pointed to the need for “some good counseling in these patients from the beginning,” saying that “you need to prepare people for what will happen.”
Many people starting a GLP-1 drug for weight loss might not be well versed on the GI side effects that can occur, which may lead to discontinuation, particularly after the initial large reductions in body weight level off, Thomsen proposed. In a recent survey conducted in Denmark, he noted, about half of respondents said they hadn’t discussed with their doctors how long they should remain on a GLP-1 receptor agonist for weight loss.
“It may very well be the case for most people that for this to be effective, they need to basically take it the rest of their lives, like antihypertensives and [lipid-lowering agents] and so on,” Thomsen said, adding that physicians should talk about that with their patients.
Denmark: Home to Novo Nordisk
Ultimately, though, cost appears to be a driving force behind high rates of discontinuation, he indicated. “As doctors, we really look forward to having these drugs [become] more affordable.”
Commenting on the findings for TCTMD, Niels Jessen, MD, PhD (Aarhus University Hospital), a member of the EASD program committee who was not involved in the study, also cited the high cost of the GLP-1 drugs as a likely reason for large proportions of patients abandoning treatment.
Novo Nordisk, the maker of Wegovy and Ozempic, which is the brand name of semaglutide when used for type 2 diabetes, is headquartered in Denmark. Jessen noted that the Danish government was initially covering the cost of these medications for weight loss through supplemental insurance but reversed course during the study period when use was greater than anticipated. That is a contributor to the high rates of discontinuation observed in this study, he said.
We therefore have to think about how we can help people that are not able to afford the cost of these drugs. Niels Jessen
The other factors associated with stopping treatment cover a broad spectrum, making it difficult to identify areas on which to focus to help keep patients on these drugs, Jessen said.
The issue is important because starting and stopping the GLP-1 receptor agonists can have detrimental effects. “Rapid discontinuation is something we do not encourage because we are afraid of this on/off use of the drugs may lead to unfavorable body composition,” he said. People tend to lose more lean muscle mass while taking the medications and then, when discontinuing, regain weight mostly in the form of fat mass, he said.
It’s unclear whether patients will need to be on GLP-1 receptor agonists for life, “but at least we would like them to contact physicians and be in a dialogue with a medical doctor before discontinuing the drug because for some of them, it may be preferable that they stay on the drug, if possible,” Jessen said.
Like Thomsen, he said the expense of the GLP-1 drugs needs to be addressed to improve adherence. “The financial burden is substantial, and we therefore have to think about how we can help people that are not able to afford the cost of these drugs.”