Institution: | 1. Centre for Diabetes and Endocrinology, Johannesburg, South Africa;2. N1 City Medical Chambers, Goodwood, Cape Town, South Africa;3. Helderberg Clinical Trials Centre, Somerset West, South Africa;4. Life Chatsmed Garden Hospital and Nelson R Mandela School of Medicine, Durban, South Africa;5. Kuils River Netcare Hospital, Cape Town, South Africa.;1. Steno Diabetes Center, Gentofte, Denmark;2. Rigshospitalet, Copenhagen, Denmark;3. Aarhus University, Denmark;4. University of Copenhagen, Denmark;1. Dallas Diabetes and Endocrine Center at Medical City, Dallas, TX, USA;2. Endocrine and Metabolic Consultants, Rockville, MD, USA;3. Institute of Life Sciences, Swansea University and Abertawe Bro Morgannwg University NHS Trust, Swansea, UK;4. Division of Endocrinology, Diabetes and Metabolism, University of Cincinnati, Cincinnati VA Medical Center, Cincinnati, OH, USA;5. Division of Endocrinology and Diabetology, University Hospital of Freiburg, Freiburg, Germany;6. Medical & Science, GLP-1 & Obesity, Novo Nordisk A/S, Soeborg, Denmark;7. Global Medical Affairs, Novo Nordisk A/S, Soeborg, Denmark;8. Department of Internal Medicine, Academic Medical Centre, Amsterdam, The Netherlands |
Abstract: | Background and aimsTo evaluate the effects of 14 weeks of liraglutide plus modest caloric restriction on lipid/lipoprotein metabolism in overweight/obese persons with prediabetes.Methods and resultsVolunteers with prediabetes followed a calorie-restricted diet (?500 Kcal/day) plus liraglutide (n = 23) or placebo (n = 27) for 14 weeks. The groups were similar in age (58 ± 7 vs. 58 ± 8 years) and body mass index (31.9 ± 2.8 vs. 31.9 ± 3.5 kg/m2). A comprehensive lipid/lipoprotein profile was obtained before and after intervention using vertical auto profile (VAP). Weight loss was greater in the liraglutide group than in the placebo group (6.9 vs. 3.3 kg, p < 0.001), as was the fall in fasting plasma glucose concentration (9.9 mg/dL vs. 0.3 mg/dL, p < 0.001). VAP analysis revealed multiple improvements in lipid/lipoprotein metabolism in liraglutide-treated compared with placebo-treated volunteers, including decreases in concentrations of total cholesterol, low-density lipoprotein cholesterol and several of its subclasses, triglyceride, and non-high-density cholesterol. The liraglutide-treated group also had a significant shift away from small, dense low-density lipoprotein-particles, as well as decreases in apolipoprotein B concentration and ratio of apolipoprotein B/apolipoprotein A-1. There were no significant changes in the lipoprotein profile in the placebo-treated group.ConclusionTreatment with liraglutide plus modest calorie restriction led to enhanced weight loss, a decrease in fasting plasma glucose concentration, and improvement in multiple aspects of lipid/lipoprotein metabolism associated with increased cardiovascular disease (CVD) risk. The significant clinical benefit associated with liraglutide-assisted weight loss in a group at high risk for CVD – obese/overweight individuals with prediabetes – as seen in our pilot study, suggests that this approach deserves further study. |