Liraglutide reduces type 2 diabetes risk in adults with prediabetes, obesity

BOSTON — More than half of adults with prediabetes and overweight or obesity randomly assigned liraglutide returned to normoglycemia at 3 years, improving their cardiometabolic profile and reducing their risk for developing type 2 diabetes, according to study findings presented here.

“This is a group that everyone is really interested in,” Ken Fujioka, MD, director of nutrition and metabolic research and director of weight management at Scripps Research Institute in La Jolla, California, said while presenting his findings. “Can you get somebody who is prediabetic, get them to lose weight, and get them back to not just a prediabetic [state], but a normal glucose state — non-impaired? Yes, you can. Roughly two-thirds of the group were able to get to that point at the end of 160 weeks if they were on the drug.”

In a 3-year randomized, double blind, placebo-controlled study, Fujioka and colleagues analyzed data from 2,254 adults with overweight or obesity, prediabetes (defined by 2010 American Diabetes Association criteria) and either high cholesterol, hypertension or both (mean age, 48 years; 76% women; mean baseline body weight, 107.6 kg; mean baseline BMI, 38.8 kg/m²). Researchers randomly assigned participants 2:1 to 3 mg subcutaneous liraglutide once daily (n = 1,501) or placebo (n = 747) for 3 years. All participants were advised on a 500 kcal/day deficit diet and a 150-minute weekly physical activity program. The primary outcome was the proportion of patients progressing to type 2 diabetes at the conclusion of the study.

Participants assigned liraglutide took on average 2.7 times longer to progress from prediabetes to type 2 diabetes over 160 weeks vs. those assigned placebo (95% CI, 1.9-3.9). Participants assigned liraglutide reduced their risk for developing type 2 diabetes by 79.3% (P < .0001). Within the cohort, 66% of liraglutide participants regressed to normoglycemia vs. 36% in the placebo group (OR = 3.6; 95% CI, 3-4.4).

“Based on Kaplan-Meier plots of cumulative probability of a diagnosis of diabetes in this study, 3% went on to type 2 diabetes vs. 11% in placebo; that’s an 80% reduction at 160 weeks,” Fujioka said. “The time to onset of type 2 diabetes is pushed out 2.7 times longer ... showing, you can do this.”

Participants in the liraglutide group also lost more body weight at 160 weeks vs. those assigned placebo (6.1% vs. 1.9%; P < .0001) and experienced greater reduction in mean waist circumference (6.9 cm vs 3.4 cm; 95% CI, -4.2 to -2.8).

Researchers found weight loss was accompanied by reductions in mean systolic blood pressure (estimated treatment difference [EDT] –3.2 mm Hg; P < .0001), total cholesterol (ETD –2.6%; P = .03), triglycerides (ETD –11.3%; P = .0003) and high-sensitivity C-reactive protein (ETD –36.9%; P < .0001).

Two deaths occurred in each group, one in the liraglutide group was cardiovascular related. Overall, major adverse events were low; 15.1% of liraglutide patients experienced serious adverse events vs. 12.9% in the placebo group. Most reported side effects were gastrointestinal. Researchers did not identify any new safety issues, Fujioka said.

“Three years of treatment was also associated with a vast majority of improved cardiometabolic risk factors,” Fujioka said. “If those factors remain improved, there is a very good shot at lowering total cardiovascular risk.”

Further research needs to be done to determine the extent to which outcomes are related to liraglutide rather than the intensive lifestyle intervention component, Fujioka said.

“How much is the drug, at this point, we can’t differentiate,” Fujioka said. “But I think the drug obviously has a big part in this in lowering of type 2 diabetes [risk].” – by Regina Schaffer

Reference :

Fujioka K, et al. OR36-1. Presented at: The Endocrine Society Annual Meeting; April 1-4, 2016; Boston.

Disclosure: Novo Nordisk sponsored this research. The researchers report various relationships with multiple pharmaceutical companies.