• Researchers have used real-world data to identify key factors for long-term weight loss for patients taking GLP-1 drugs like Ozempic and Wegovy.
• The study identified the type of medication, dosage, treatment indication, and medication persistence as four of the most important factors.
• GLP-1 drugs are powerful agents for weight loss, but cost and access are still barriers for many Americans.

Millions of Americans have taken Ozempic or similar GLP-1 drugs to lose weight, but sustaining that weight loss long-term has proved difficult for many of them.

However, new research suggests there are four factors that could be key to improving these outcomes.

Researchers from the Cleveland Clinic looked at electronic health records of nearly 3,400 patients prescribed one of two different GLP-1 drugs — semaglutide ( sold under the brand names Ozempic and Wegovy) and liraglutide (sold under the brand names Saxenda and Victoza) — to see how various factors like dosage, indication, and biological sex affected weight loss at one year.

Their findings were published this month in Jama Network Open.

Researchers looked at how these factors affected weight loss in two ways: total percentage change in body weight and whether an individual lost 10% or more of their body weight. The 10% mark is clinically significant, as hitting that benchmark is known to improve other comorbidities like high blood pressure and chronic disease risk.

They identified four factors that appear to be the most significant for long-term weight loss, some of them obvious and others more complex:

• The type of medication (active ingredient) – Did the patient use semaglutide or liraglutide?
• The dosage – Was the patient using a high or low-maintenance dose?
• Treatment indication – Was the medicine prescribed for type 2 diabetes or obesity?
• Medication persistence – Did the patient have any gaps in access to their medication?

“Our findings provide timely data on longer-term weight outcomes in patients receiving treatment with injectable semaglutide or liraglutide for obesity or type 2 diabetes, as well as identify key characteristics that could inform the probability of achieving sustained weight loss of a magnitude large enough to provide clinically significant health benefits,” Hamlet Gasoyan, PhD, lead author of the study and a researcher with Cleveland Clinic’s Center for Value-Based Care Research, told Healthline.

How the four key factors impacted sustained weight loss

Gasoyan and his team used the Cleveland Clinic electronic health records for 3,389 patients who were prescribed either semaglutide or liraglutide from July 2015 through June 2022. In order to be included, patients had to have a BMI of at least 30, indicating the person had obesity.

More than half the patients were female (54%) and had an average age of 50. The cohort was predominantly white (68%) but included significant Black (20%) and Hispanic (7%) populations.

At the one-year mark, four factors appeared to have the largest influence on sustained weight loss. Here’s how they affected whether or not patients would achieve 10% or greater weight loss:

• Active agent: Patients who took semaglutide were more than twice as likely compared to those taking liraglutide.
• Indication: Those prescribed their medication for obesity were also more than twice as likely than those with type 2 diabetes.
• Dosage: Patients taking a higher maintenance dose of their medication were 1.5 times more likely than those taking a lower dose.
• Persistence: patients with persistent coverage (access to their medication) were more than three times as likely as those who had the least access.

Patient sex was also an important factor. Females in the study were 1.5 times as likely to hit the 10% benchmark as males.

Two of the factors may seem obvious: active agent and dosage. Basically, the kind of medication prescribed and dosage affected the weight loss outcome.

Semaglutide resulted in more than double the average weight loss of liraglutide (5.1% versus 2.2%). However, that’s nothing new: prior studies have shown that semaglutide is simply more effective for weight loss than liraglutide.

Evidence has also pointed to higher maintenance doses of semaglutide being more effective for weight loss than lower doses.

Indication is complicated. The evidence is clear that patients prescribed a GLP-1 for obesity tend to lose more weight than those with type 2 diabetes, but why that’s the case isn’t so obvious.

Caroline Apovian MD, a Professor of Medicine at Harvard Medical School and the co-director of the Center for Weight Management and Wellness at Brigham and Women’s Hospital, told Healthline that these findings are essentially confirmatory of prior research.

It’s the fourth factor — persistence — that has grabbed the attention of Apovian and other obesity experts.

Persistence is the biggest key

“What this study adds is really diving into that persistence question. Nowadays, the conversation tends to focus on the idea that these are really great medications, but are patients actually taking them?” Beverly Tchang, MD, an endocrinologist, Spokesperson for the Obesity Society, and Assistant Professor of clinical medicine at Weill Cornell Medicine, told Healthline.

“This creates a very clear relationship between that persistence and the degree of weight loss,” she said.

As effective as GLP-1 drugs are, access has proven to be a major roadblock for many Americans. With the soaring popularity of these drugs, patients across the United States have faced shortages, with manufacturers unable to keep up with demand.

Cost and insurance coverage have also been problematic for many patients. The monthly cost for GLP-1 drugs can easily reach $1,000 or more before any insurance coverage or rebates are applied.

If patients can’t afford their medication or can’t access it, they won’t take it. It’s as simple as that.

This latest research helps to illustrate that dilemma.

Gasoyan and his team found that at the one-year mark, only 40% of patients had persistent medication coverage, which they defined as a cumulative lapse in coverage of less than 90 days.

But those that did have persistent coverage demonstrated significantly more weight loss (5.5%) compared to those with the least (1.8%) — less than 90 days of coverage for the year.

The data “reinforces that persistence is key to achieving meaningful weight outcomes with these medications,” said Gasoyan.

“If we avoid therapeutic interruptions with these medications, whether that be due to shortages or insurance coverage, then we will have better persistence with these medications and more weight loss,” added Tchang.

The bottom line

GLP-1 drugs like Ozempic and Wegovy are powerful weight-loss tools. However, long-term weight loss outcomes can be affected by a variety of factors.

In a new study, researchers identified four of the most important factors for long-term weight loss in patients taking a GLP-1 drug. These include the kind of medication, the dosage, the indication, and medication persistence (how long the patient continuously took the medication).

Medication persistence is essential to long-term weight loss, however access and cost related to GLP-1 drugs continue to be roadblocks for many Americans.