Adverse GI Events Have Little Impact on Weight Loss Seen with Semaglutide vs other GLP-1 RAs

New data from analysis of 3 SUSTAIN trials suggests the superior weight loss seen with once-weekly semaglutide (Ozempic) versus other GLP-1 receptor agonists was not driven by incidence of adverse gastrointestinal events.

While results suggest those who experienced nausea or vomiting experienced a slightly greater degree of weight loss, results from the analysis indicate these events had a little to do with the superior weight loss seen with semaglutide use.

“Treatment with semaglutide resulted in a significantly greater weight loss than with exenatide ER, dulaglutide, or liraglutide, also in subjects who did not experience nausea/vomiting, suggesting that the superior weight loss observed with semaglutide was not related to the occurrence of these events,” wrote study investigators.

With many subscribing to the notion that incidence of gastrointestinal adverse events could contribute to greater weight loss seen with some GLP-1 receptor agonists, a team led by Ildiko Lingvay, MD, sought to compare how incidence of 5 different gastrointestinal adverse events impacted weight loss from patients within SUSTAIN 3, 7, and 10. With data from these 3 trials, investigators hoped to compare the effects of semaglutide against exenatide, dulaglutide, and liraglutide during dose escalation and from baseline to end of treatment.

Using data from the 3 trials, investigators categorized patients based on whether or not they reported instances of nausea, vomiting, diarrhea, constipation, or dyspepsia. Investigators went on to perform a mediation analysis using this data to separate weight loss into direct or indirect effects.

Investigators noted the baseline characteristics were similar between the 3 SUSTAIN trials chosen for inclusion, with the exception of a longer diabetes duration among those in SUSTAIN 3 (exenatide) and SUSTAIN 10 (liraglutide) compared to those in SUSTAIN 7 (dulaglutide). Additionally, initial analysis suggested patients experiencing gastrointestinal adverse events were more likely to have a lower baseline body weight than those not reporting events across all 3 trials.

Upon analysis, the nausea/vomiting-mediated difference for weight loss from baseline to week 12 and end of treatment, respectively, with semaglutide use were 0.05 kg and 0.09 kg of 3.78 kg at end of treatment against exenatide and 0.05 kg and 0.09 kg of 3.82 kg at end of treatment versus liraglutide. In comparisons against dulaglutide, the mediated difference for weightless to week 12 and end of treatment, respectively, with semaglutide use were 0.06 and 0.03 kg of 2.26 at end of treatment in the low-dose comparison and 0.08 and 0.04 of 3.55 kg at end of treatment in the high-dose comparison.

Results of the analysis indicated bodyweight reductions with all 4 GLP-1 receptors agonists were consistently greater among patients who experienced nausea/vomiting than among those who did not. Additionally, reductions with semaglutide were consistently greater than those with the other GLP-1 receptor agonists regardless of nausea and vomiting.

“Because gastrointestinal adverse events including nausea, vomiting, or diarrhea are the most common type of adverse events with GLP-1 receptor agonists, it is important to establish whether the weight loss difference between treatment is mediated through the occurrence of gastrointestinal adverse events,” wrote study investigators.

This study, “Superior weight loss with once-weekly semaglutide versus other glucagon-like peptide-1 receptor agonists is independent of gastrointestinal adverse events,” was published in BMJ Open Diabetes Research and Care.