As an adjunct to a reduced-calorie diet and increased physical activity, liraglutide decreased type 2 diabetes risk compared with placebo in overweight or obese patients with prediabetes, according to results published in the Lancet.
The randomized double-blind placebo-controlled SCALE trial (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) evaluated whether liraglutide decreased the risk of developing type 2 diabetes compared with placebo in overweight or obese patients with prediabetes. SCALE included 2254 adults from 191 clinical research sites in 27 countries. Patients had prediabetes and a body mass index (BMI) of ≥30 kg/m2, or ≥27 kg/m2 with comorbidities.
Researchers randomly assigned patients 2:1 to once-daily subcutaneous liraglutide (3 mg; n=1505) or placebo (n=749), in addition to a reduced-calorie diet and increased physical activity.
The primary outcome was defined as time to diabetes onset at 160 weeks, which was determined in all randomly assigned treated patients with at least one post-baseline evaluation.
After withdrawal of 47% of patients in the liraglutide group and 55% of patients in the placebo group, the remaining 50% of study participants completed 160 weeks of study participation.
At week 160, 2% of liraglutide patients vs 6% of placebo patients were diagnosed with diabetes while on treatment, with a mean time from random assignment to diagnosis of 99 weeks in the liraglutide group and 87 weeks in the placebo group.
Once the researchers factored in the different diagnosis frequencies between treatment groups, they observed that time to diabetes onset in all randomized individuals at 160 weeks was 2.7 times longer with liraglutide than placebo (95% CI, 1.9-3.9; P <.0001). The corresponding hazard ratio for liraglutide was 0.21 (95% CI, 0.13-0.34).
In addition, weight loss was greater with liraglutide than placebo at week 160 (–6.1 vs. –1.9%; estimated treatment difference, –4.3%; 95% CI, –4.9 to –3.7; P <.0001).
The rate of serious adverse events was 15% in the liraglutide arm compared with 13% in the placebo arm.
Despite this limitation, the researchers concluded that 3-mg laraglutide was generally well tolerated and, as a glucagon-like peptide-1 receptor agonist, “provides a different treatment option for individuals with obesity or overweight, with or without type 2 diabetes, having direct glucose-dependent effects on insulin secretion and weight-loss mediated effects on improved insulin resistance. However, post-market surveillance will be exercised to ensure detection of potential side effects with a very low incidence.”
The researchers report numerous financial disclosures with pharmaceutical companies.
le Roux CW, Astrup A, Fujioka K, et al. 3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial [published online Feb. 22]. Lancet. 2017; doi:10.1016/S0140-6736(17)30315-X