Early Response to Liraglutide Predicted Significant Weight Loss Later

Weight loss linked to hot flash reduction
Weight loss linked to hot flash reduction
Patients who lost weight with liraglutide after 16 weeks achieved clinically significant weight loss at 56 weeks.

Patients who lost weight with liraglutide early on in the SCALE trials experienced greater cardiometabolic benefits at 56 weeks compared with those who did not, according to study results presented at ObesityWeek 2016 and published simultaneously in Obesity.

“One strategy to increase benefit versus risk in obesity pharmacotherapy is through identification of long-term weight loss predictors,” researchers wrote. “By stopping drug therapy early in patients unlikely to achieve clinical benefit, clinicians can minimize drug exposure, improve the benefit: risk ratio for the patient, and use health resources more effectively.”

For this analysis, researchers used pooled data from the SCALE Obesity and Prediabetes (Effect of Liraglutide on Body Weight in Non-diabetic Obese Subjects or Overweight Subjects With Co-morbidities: SCALE™ – Obesity and Pre-diabetes; ClinicalTrials.gov identifier: NCT01272219) and SCALE Diabetes (Effect of Liraglutide on Body Weight in Overweight or Obese Subjects With Type 2 Diabetes: SCALE™ – Diabetes; ClinicalTrials.gov identifier: NCT01272232) to ascertain the optimal treatment time and weight loss threshold for identifying patients who would achieve clinically meaningful weight loss after 56 weeks of treatment with liraglutide 3.0 mg.

Results showed that early response to treatment (defined as weight loss of at least 4% after 16 weeks of treatment with liraglutide) was the best predictor of achieving at least 5% weight loss at 56 weeks.

The researchers found that 77.3% of patients without type 2 diabetes were early responders and 22.7% were early nonresponders. Among those with type 2 diabetes, 62.7% were early responders and 37.3% were nonresponders.

At 56 weeks, mean weight loss was greater among early responders vs early nonresponders for both patients without type 2 diabetes (10.8% vs 3%) and those with type 2 diabetes (8.5% vs 3.1%). Further, in both trials, more early responders than early nonresponders achieved 5%, greater than 10%, and greater than 15% weight loss at week 56. A similar pattern was noted with placebo, but proportions were much smaller than with liraglutide.

Additionally, compared with early nonresponders, early responders experienced greater improvements in cardiometabolic risk factors, including systolic blood pressure, HDL cholesterol, LDL cholesterol, total cholesterol, and triglycerides at week 56.

In terms of safety, the rates of adverse events were generally similar between early responders and early nonresponders.

“From a clinical perspective, use of the stopping rules should help optimize the use of liraglutide 3.0 mg for weight management,” the researchers noted. “Patients can be informed that, if they respond well during the first 16 weeks, it is likely they will continue to do so.”

However, they noted that “the results should be interpreted with  as they are not comparisons between randomized groups and were therefore not subjected to significance testing.” Other study limitations included the low number of patients in the liraglutide early nonresponder and placebo early responder groups, the use of forced liraglutide dose escalation in the original trials, and the potential for smaller effect size in a real-world setting.

Disclosures: The preparation of this article was supported by Novo Nordisk A/S, which also sponsored the SCALE trials.

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  1. Fujioka K, O’Neil P, Davies M, et al. Early Weight Loss with Liraglutide 3.0 mg Predicts 1-Year Weight Loss and is Associated with Improvements in Clinical Markers. Obesity. 2016 Nov 2. doi:10.1002/oby.21629 [Epub ahead of print].