Liraglutide improves weight, HbA1c in adults with overweight/obesity, type 2 diabetes

SAN DIEGO — More patients with overweight and obesity achieved clinically meaningful weight loss with liraglutide 3 mg and 1.8 mg compared with placebo, according to research presented here.

Patients who responded to liraglutide (Saxenda, Victoza; Novo Nordisk) achieved a total weight loss of approximately 10% and greater improvements in HbA1c, suggesting an additional treatment benefit, with the rates of adverse events similar at both doses.

“Obesity is a major health care problem in the U.S. and westernized countries,” Ralph DeFronzo, MD, of the University of Texas Health Science Center, San Antonio, told Endocrine Today. “With the approval of Saxenda by the FDA, we now have another therapy that can be used in combination with diet and exercise to help our patients lose weight and most importantly maintain the weight loss.”

Ralph DeFronzo

In a subgroup analysis of the 56-week, randomized, double blind, placebo-controlled SCALE Diabetes trial, DeFronzo and colleagues compared the efficacy and safety of liraglutide in responders (weight loss ≥ 5% from baseline to week 56) and nonresponders.

The main trial randomly assigned 846 individuals 2:1:1 to liraglutide 3 mg (n = 423), 1.8 mg (n = 211) or placebo (n = 212) in addition to diet and exercise; the mean age of the patients (50% men) was 54.9 years; BMI, 37.1 kg/m²; HbA1c, 7.9%; and type 2 diabetes duration, 7.3 years.

For the analysis, the researchers assessed the mean changes from baseline in efficacy using least-squares and safety through observation, both based on last observation carried forward. Mean pulse rate was calculated for patients who completed the trial through observation.

The mean weight loss for responders vs. nonresponders was similar with liraglutide 3 mg (10.3% vs. 1.6%) and liraglutide 1.8 mg (10.4% vs. 1.3%), both higher than placebo (9.7% vs. 0.7%). There were more responders with liraglutide 3 mg (49.9%; n = 205) and liraglutide 1.8 mg (35.6%; n = 72) than placebo (13.8%; n = 29; P < .0001).

From baseline, HbA1c changes with liraglutide 3 mg and 1.8 mg compared with placebo were –1.6% and –1.5% vs. –1.1% for responders, and –1% and –1% vs. –0.2% for nonresponders. Systolic blood pressure diminished by –5 mm Hg, –6.2 mm Hg and –5.3 mm Hg in responders with liraglutide 3 mg, liraglutide 1.8 mg and placebo, respectively, and in nonresponders by –0.5 mm Hg, –1.9 mm Hg and 0.5 mm Hg.

Based on the Impact of Weight on Quality of Life-Lite Questionnaire, physical function scores improved in responders by 19, 16.4 and 15.5 with liraglutide 3 mg, liraglutide 1.8 mg and placebo, respectively, compared with 11.1, 10.4 and 7.7 in nonresponders.

Among responders and nonresponders, reports of adverse events were similar with liraglutide 3 mg (96% vs. 92%) and liraglutide 1.8 mg (96% vs. 90%), both slightly higher than placebo (94% vs. 85%); no noticeable difference was seen between responders and nonresponders for serious adverse events.

Gastrointestinal disorders were reported most frequently in responders vs. nonresponders for liraglutide 3 mg (76% vs. 55%), but not for liraglutide 1.8 mg (58% vs. 57%) or placebo (41% vs. 39%).

Documented symptomatic hypoglycemia (plasma glucose ≤ 56 mg/dL) rates, based on events per patient year, were similar among responders and nonresponders for liraglutide 3 mg (0.9 vs. 0.8), liraglutide 1.8 mg (0.8 vs. 1.1) and placebo (0.1 vs. 0.3).

From baseline, the mean change in pulse rate (standard deviation) for liraglutide 3 mg, liraglutide 1.8 mg and placebo was 1.3 (9.5), 2 (10.7) and –4.4 (10.1) beats per minute for responders and 3.5 (10.2), 3.1 (10.1) and –1.2 (9) for nonresponders. – by Allegra Tiver

Reference:

DeFronzo R, et al. Abstract OR07-6. Presented at: The Endocrine Society Annual Meeting; March 5-8, 2015, San Diego.

Disclosure: DeFronzo reports relationships with Amylin Pharmaceuticals, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Jansen Pharmaceuticals, Lexicon Pharmaceuticals, Novo Nordisk and Takeda.