The role of glucagon like peptide - 1 (GLP-1) receptor agonists in the treatment of type 2 diabetes mellitus

Background and Aims: Type 2 diabetes mellitus (T2DM) is multifactorial, affected by obesity, blood pressure (BP) and cardiovascular disease (CVD). The therapeutic effects of GLP-1 in managing BP and increasing satiety promoting weight loss prove beneficial against these risk factors. This literature review aims to assess current evidence on the efficacy of GLP-1 receptor agonists (GLP-1RA) for T2DM treatment.Methods: A PubMed literature search over the preceding 5 years was carried out using keywords including GLP-1 receptor agonists and obesity, hypertension and CVD. A total of 7 studies were analysed.Results: Obesity: A meta-analysis showed a 3kg weight reduction by GLP-1RA compared to other active therapies. The SCALE diabetes study confirmed that Liraglutide 3.0mg brought about a 6.0% weight reduction. Liraglutide use sufficiently reduced HbA1c (-1.3) that 57.0% of patients achieved target HbA1c of u22646.5% compared to placebo (-0.3 HbA1c reduction, 15.0% HbA1c u22646.5%), and significantly reduced the use of other antiglycaemic drugs also. BP control: Mice studies showed atrial GLP-1 receptor stimulation promoted secretion of atrial natriuretic peptide and lowering of BP. A 12 week treatment of Liraglutide in obese T2DM patients also lowered BP (-5.30; 95% CI, -7.90 to -2.60; P < 0.001) and increased weight loss (-5.03; 95% CI, -5.81 to -3.80; P < 0.001). CV effects: ELIXA study showed no significant change (P = 0.81) in heart failure risk with Lixisenatide (hazard ratio 0.96; 95% CI, 0.89 to 1.17) or rate of death (hazard ratio 0.94; 95% CI, 0.75 to 1.23). LEADER and SUSTAIN-6 studies showed significant reductions in CV risk using Liraglutide (0.87; 95% CI, 0.78 to 0.97; P=0.01) and Semiglutide (0.74; 95% CI, 0.58 to 0.95; P < 0.001) respectively, along with reductions in HbA1c, body weight and BP therefore providing cardiac protection. Conclusion: GLP-1RA, by appetite regulation and BP control, could slow down progression of T2DM and death by CVD. The studies explored in this review suggest that GLP-1RA could have a place much earlier in T2DM treatment than where current guidelines suggest. Further research to assess long term outcomes is recommended.