Benefits of Liraglutide Treatment in Overweight and Obese Older Individuals With Prediabetes

Abstract

OBJECTIVEThe aim was to evaluate the ability of liraglutide to augment weight loss and improve insulin resistance, cardiovascular disease (CVD) risk factors, and inflammation in a high-risk population for type 2 diabetes (T2DM) and CVD.RESEARCH DESIGN AND METHODSWe randomized 68 older individuals (mean age, 58 ± 8 years) with overweight/obesity and prediabetes to this double-blind study of liraglutide 1.8 mg versus placebo for 14 weeks. All subjects were advised to decrease calorie intake by 500 kcal/day. Peripheral insulin resistance was quantified by measuring the steady-state plasma glucose (SSPG) concentration during the insulin suppression test. Traditional CVD risk factors and inflammatory markers also were assessed.RESULTSEleven out of 35 individuals (31%) assigned to liraglutide discontinued the study compared with 6 out of 33 (18%) assigned to placebo (P = 0.26). Subjects who continued to use liraglutide (n = 24) lost twice as much weight as those using placebo (n = 27; 6.8 vs. 3.3 kg; P < 0.001). Liraglutide-treated subjects also had a significant improvement in SSPG concentration (−3.2 vs. 0.2 mmol/L; P < 0.001) and significantly (P ≤ 0.04) greater lowering of systolic blood pressure (−8.1 vs. −2.6 mmHg), fasting glucose (−0.5 vs. 0 mmol/L), and triglyceride (−0.4 vs. −0.1 mmol/L) concentration. Inflammatory markers did not differ between the two groups, but pulse increased after liraglutide treatment (6.4 vs. −0.9 bpm; P = 0.001).CONCLUSIONSThe addition of liraglutide to calorie restriction significantly augmented weight loss and improved insulin resistance, systolic blood pressure, glucose, and triglyceride concentration in this population at high risk for development of T2DM and CVD.

Glucagon-Like Peptide-1 Receptor Agonists for Diabetes Mellitus

“…There may be a role for GLP-1 agonists in patients with prediabetes and cardiovascular risk factors, but this requires further study. 88,89 In conclusion, cardiovascular risk factor reduction offers a compelling rationale to incorporate GLP-1 agonist therapy early in the management of diabetes mellitus in patients at risk for cardiovascular disease.…”

Incretin-based therapies in prediabetes: Current evidence and future perspectives

“…Mean change in plasma GLU during OGTT were reduced in all LIRA groups compared with that of orlistat and placebo. Median β-cell function increased in the LIRA arm by 5%-24% Kim et al [86] 68 overweight/obese individuals with IFG and/or IGT 14 wk double blind randomized placebo-controlled study. 24 individuals received LIRA 1.8 mg daily and 27 placebo therapy Participants randomized to LIRA arm lost twice as much weight as those assigned to placebo (P < 0.001).…”

“…Recently, a 14-wk double blind, randomized placebocontrolled study was launched in order to investigate the possible role of liraglutide 1.8 mg treatment in 68 older (mean age: 58 ± 8 years) overweight/obese (mean BMI: 31.9 kg/m 2 ) individuals with prediabetes (IFG and/or IGT) [86] . Participants were also advised to eat a moderate carbohydrate diet and decrease total caloric intake by 500 kcal/d.…”

“…In this view, it is unclear what the net effect would be when they are administered in individuals with prediabetes. In order to investigate this observation, a parallel study was organized in order to evaluate the relative impact of the indirect effect of weight loss and increase insulin sensitivity compared to the direct effect of GLP-1R agonists on β-cell function [86,87] . In this recent double-blind, randomized, placebo-controlled, parallel-group study 49 individuals (mean age: 58 years, mean BMI: 32.9 kg/m 2 ) with prediabetes (isolated IFG, isolated IGT and combined IFG/IGT) received either liraglutide 1.8 mg daily (n = 24) or placebo (n = 25).…”

Obesity: A Review of Pathogenesis and Management Strategies in Adult

“…If a patient does not reach this target, the drug should be discontinued. [70][71][72][73][93][94][95][96][97] The efficacy and safety of the drug were assessed in the following RCTs: SCALE-Maintenance 98 , SCALE-Obesity 99 and LEADER [100][101][102] . Liraglutide is generally well tolerated.…”