14 research outputs found
A randomised, open label, active comparator trial assessing the effects of 26âweeks of liraglutide or sitagliptin on cardiovascular function in young obese adults with type 2 diabetes
Aim
To compare the effects of a glucagonâlike peptideâ1 receptor agonist and a dipeptidyl peptidaseâ4 inhibitor on magnetic resonance imagingâderived measures of cardiovascular function.
Materials and methods
In a prospective, randomized, openâlabel, blinded endpoint trial liraglutide (1.8 mg) and sitagliptin (100âmg) were compared in asymptomatic, nonâinsulin treated young (aged 18â50âyears) adults with obesity and type 2 diabetes. The primary outcome was difference in circumferential peak early diastolic strain rate change (PEDSR), a biomarker of cardiac diastolic dysfunction 26âweeks after randomization. Secondary outcomes included other indices of cardiac structure and function, HbA1c and body weight.
Results
Seventyâsix participants were randomized (54% female, meanâ±âSD age 44â± 6âyears, diabetes duration 4.4âyears, body mass index 35.3â±â6.1 kgâmâ2), of whom 65% had â„1 cardiovascular risk factor. Sixtyâone participants had primary outcome data available. There were no statistically significant betweenâgroup differences (intentionâtoâtreat; mean [95% confidence interval]) in PEDSR change (â0.01 [â0.07, +0.06] sâ1), left ventricular ejection fraction (â1.98 [â4.90, +0.94]%), left ventricular mass (+1.14 [â5.23, +7.50] g) or aortic distensibility (â0.35 [â0.98, +0.28] mmHgâ1âĂâ10â3) after 26âweeks. Reductions in HbA1c (â4.57 [â9.10, â0.37] mmolâmolâ1) and body weight (â3.88 [â5.74, â2.01] kg) were greater with liraglutide.
Conclusion
There were no differences in cardiovascular structure or function after shortâterm use of liraglutide and sitagliptin in younger adults with obesity and type 2 diabetes. Longer studies in patients with more severe cardiac dysfunction may be necessary before definitive conclusions can be made about putative pleiotropic properties of incretinâbased therapies
Efficacy and safety of glucagon-like peptide-1 receptor agonists in type 2 diabetes: A systematic review and mixed-treatment comparison analysis
AIMS: To compare efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in people with type 2 diabetes. MATERIALS AND METHODS: We electronically searched, up to June 3, 2016, published randomized clinical trials lasting between 24 and 32âweeks that compared a GLP-1RA (albiglutide, dulaglutide, twice-daily exenatide and once-weekly exenatide, liraglutide, lixisenatide, semaglutide and taspoglutide) with placebo or another GLP-1RA. Data on cardiometabolic and safety outcomes were analysed using a mixed-treatment comparison meta-analysis. RESULTS: A total of 34 trials (14â464 participants) met the inclusion criteria; no published data for semaglutide were available. Compared with placebo, all GLP-1RAs reduced glycated haemoglobin (HbA1c) and fasting plasma glucose (FPG) levels (reductions ranged from -0.55% and -0.73âmmol/L, respectively, for lixisenatide to -1.21% and -1.97âmmol/L, respectively, for dulaglutide). There were no differences within short-acting (twice-daily exenatide and lixisenatide) or long-acting (albiglutide, dulaglutide, once-weekly exenatide, liraglutide and taspoglutide) groups. Compared with twice-daily exenatide, dulaglutide treatment was associated with the greatest HbA1c and FPG reduction (0.51% and 1.04âmmol/L, respectively), followed by liraglutide (0.45% and 0.93âmmol/L, respectively) and once-weekly exenatide (0.38% and 0.85âmmol/L, respectively); similar reductions were found when these 3 agents were compared with lixisenatide. Compared with placebo, all GLP-1RAs except albiglutide reduced weight and increased the risk of hypoglycaemia and gastrointestinal side effects, and all agents except dulaglutide and taspoglutide reduced systolic blood pressure. When all GLP-1RAs were compared with each other, no clinically meaningful differences were observed in weight loss, blood pressure reduction or hypoglycaemia risk. Albiglutide had the lowest risk of nausea and diarrhoea and once-weekly exenatide the lowest risk of vomiting. CONCLUSIONS: The RCTs in the present analysis show that all GLP-1RAs improve glycaemic control, reduce body weight and increase the risk of adverse gastrointestinal symptoms compared with placebo. Although there were no differences when short-acting agents were compared with each other or when long-acting agents were compared with each other, dulaglutide, liraglutide and once-weekly exenatide were superior to twice-daily exenatide and lixisenatide at lowering HbA1c and FPG levels. There were no differences in hypoglycaemia between these 3 agents, whilst once-weekly exenatide had the lowest risk of vomiting. These results, along with patient's preferences and individualized targets, should be considered when selecting a GLP-1RA.National Institute for Health Research, Lifestyle & Physical ActivityPeer-reviewedPost-prin
Efficacy and safety of glucagon-like peptide-1 receptor agonists in type 2 diabetes: A systematic review and mixed-treatment comparison analysis
AIMS: To compare efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in people with type 2 diabetes. MATERIALS AND METHODS: We electronically searched, up to June 3, 2016, published randomized clinical trials lasting between 24 and 32âweeks that compared a GLP-1RA (albiglutide, dulaglutide, twice-daily exenatide and once-weekly exenatide, liraglutide, lixisenatide, semaglutide and taspoglutide) with placebo or another GLP-1RA. Data on cardiometabolic and safety outcomes were analysed using a mixed-treatment comparison meta-analysis. RESULTS: A total of 34 trials (14â464 participants) met the inclusion criteria; no published data for semaglutide were available. Compared with placebo, all GLP-1RAs reduced glycated haemoglobin (HbA1c) and fasting plasma glucose (FPG) levels (reductions ranged from -0.55% and -0.73âmmol/L, respectively, for lixisenatide to -1.21% and -1.97âmmol/L, respectively, for dulaglutide). There were no differences within short-acting (twice-daily exenatide and lixisenatide) or long-acting (albiglutide, dulaglutide, once-weekly exenatide, liraglutide and taspoglutide) groups. Compared with twice-daily exenatide, dulaglutide treatment was associated with the greatest HbA1c and FPG reduction (0.51% and 1.04âmmol/L, respectively), followed by liraglutide (0.45% and 0.93âmmol/L, respectively) and once-weekly exenatide (0.38% and 0.85âmmol/L, respectively); similar reductions were found when these 3 agents were compared with lixisenatide. Compared with placebo, all GLP-1RAs except albiglutide reduced weight and increased the risk of hypoglycaemia and gastrointestinal side effects, and all agents except dulaglutide and taspoglutide reduced systolic blood pressure. When all GLP-1RAs were compared with each other, no clinically meaningful differences were observed in weight loss, blood pressure reduction or hypoglycaemia risk. Albiglutide had the lowest risk of nausea and diarrhoea and once-weekly exenatide the lowest risk of vomiting. CONCLUSIONS: The RCTs in the present analysis show that all GLP-1RAs improve glycaemic control, reduce body weight and increase the risk of adverse gastrointestinal symptoms compared with placebo. Although there were no differences when short-acting agents were compared with each other or when long-acting agents were compared with each other, dulaglutide, liraglutide and once-weekly exenatide were superior to twice-daily exenatide and lixisenatide at lowering HbA1c and FPG levels. There were no differences in hypoglycaemia between these 3 agents, whilst once-weekly exenatide had the lowest risk of vomiting. These results, along with patient's preferences and individualized targets, should be considered when selecting a GLP-1RA