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NASHVILLE -- Gastrointestinal adverse events, such as nausea and vomiting, were not responsible for the weight loss that patients achieved on liraglutide (Saxenda), researchers said here.
Among 3,000 patients who were overweight or obese and who did not have type 2 diabetes, more than 68% taking 3-mg daily liraglutide plus diet and exercise (n=2,487) experienced GI adverse effects versus 40% of those on placebo (n=1,244), reported , at the University of Calgary, in Alberta, and colleagues.
Action Points
- Note that these studies were published as abstracts and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
- Gastrointestinal adverse events, such as nausea and vomiting, were not responsible for the weight loss that patients achieved on liraglutide.
- Note that the injectable obesity drug was associated with a greater weight loss versus placebo from baseline.
The injectable obesity drug was associated with a greater weight loss versus placebo from baseline (8.0% versus 2.6%, P<0.0001), they stated in a presentation at the American Association of Clinical Endocrinologists annual meeting.
There was no significant difference in weight loss between those who experienced more than a week of nausea or vomiting and those who didn't, regardless of treatment: patients on liraglutide who had these symptoms lost weight (-7.8%) as did those with no symptoms (-8.1%). Patients on placebo with symptoms also lost weight (-2.5%) along with those without symptoms (-2.6%, P=0.81), the authors found.
There had been worries that the weight loss patients experienced was due to the adverse effects of the hunger-suppressing drug, Lau explained.
"The GI side effects -- mainly nausea, vomiting, and diarrhea -- did not in any way contribute to more or less weight loss," Lau told 鶹ý. "The efficacy of liraglutide is not related in any way to GI side effects."
The FDA approved liraglutide for weight loss in late 2014. An investigation by 鶹ý and the Milwaukee Journal Sentinel examined the unresolved concerns surrounding the safety of diet drugs. For every eight people on Saxenda, that report found, one will get nausea. The drug is a higher dose of the type 2 diabetes drug Victoza, which was the primary suspect in more than 3,000 hospitalizations for pancreatitis.
Based on their year-long post-hoc analysis, Lau's group reported that the most prevalent GI adverse effects were nausea (40.2% of those on the drug versus 14.7% on placebo), diarrhea (20.9% versus 9.3%), constipation (20.0% versus 8.7%), and vomiting (16.3% versus 4.1%). Most of these occurred during the first 16 weeks of the trial, which lasted for 56 weeks.
"Similar results were seen if all other types of GI adverse events combined were included," the authors wrote.
The majority of the study participants were female (mean age 45.1) with an average body mass index of 38 kg/m2. They had at least one comorbidity (61% prediabetes).
At week 56, there were no significant differences among patients who had zero, one, two to three, or more than four GI adverse events in the first 16 weeks (7.7%-8.2% for those on liraglutide and 2.3%-3.0% for those on placebo, P=0.24).
The same was true when researchers analyzed the adverse events over the entire 56 weeks (7.7%-8.4% for liraglutide and 2.4%-3.2% for placebo, P=0.55).
"Although those experiencing zero GI adverse events appeared to perform slightly better than the other groups, this may be explained by the higher withdrawal rate as the number of GI adverse event increase," the researchers wrote. "These results were further supported by comparable mean weight-loss profiles over time across the 0, 1, 2-3, or ≥4 GI adverse event groups."
There were more withdrawals in the placebo group than in the liraglutide group, Lau pointed out.
In a separate study of the same patient population, Lau's group found that those who responded early to 3.0 mg of liraglutide per day, and completed 56 weeks of treatment, had better outcomes than those who didn't respond early. They also had similar safety outcomes, they said.
For this subanalysis, outcomes of early responders (who had greater than 4% weight loss at 16 weeks) were compared against those who didn't respond early.
At 16 weeks, 80.2% of those on liraglutide and 33.1% of those on placebo had met the criteria for early responder. After 56 weeks, early responders lost 10.8% of body weight compared with 3.0% of nonresponders. Greater improvements were seen for glycemic outcomes, cardiovascular risk markers, and quality of life in early responders, the group wrote.
The safety profiles of early responders and nonresponders on liraglutide were similar:
- GI adverse event: 68.3% versus 62.5%
- Psychiatric disorders: 8.7% versus 7.3%
- Cardiac events: 3.2% versus 4.8%
- Neoplasms: 2.9% versus 2.5%
- Spontaneously reported hypoglycemia: 1.5% versus 1.4%
However, more early responders reported gallbladder-related adverse events (2.7% versus 1.1% for nonresponders).
"Applying an early discontinuation criterion (as per recently approved weight-loss medicines) would optimize clinical benefits with liraglutide 3.0 mg in weight management," the authors stated.
Disclosures
Both studies were funded by Novo Nordisk.
Lau disclosed relevant relationships with Novo Nordisk, Abbott Laboratories, AstraZeneca, Bristol Myers Squibb, Eli Lilly, GlaxoSmithKline, Merck and Co., Oryx, Pfizer, Roche, sanofi-aventis, and Solvay.
Primary Source
American Association of Clinical Endocrinologists
Source Reference: Lean M, et al "The impact of gastrointestinal adverse events on weight loss with liraglutide" AACE 2015; Abstract 2180335.
Secondary Source
American Association of Clinical Endocrinologists
Source Reference: Lau D, et al "Early responders to liraglutide 3.0 mg as an adjunct to diet and exercise form the scale obesity and prediabetes trial: Efficacy and safety results" AACE 2015; Abstract 2172494.