Understanding the place for GLP‐1RA therapy: Translating guidelines for treatment of type 2 diabetes into everyday clinical practice and patient selection

Abstract

Since the first glucagon‐like peptide 1 (GLP‐1) receptor agonist (GLP‐1RA) was approved in 2005 (exenatide twice daily) for type 2 diabetes (T2D), the class has developed with newer compounds having more pronounced effects on glycaemic control and body weight. Also, administration regimes have become more convenient with once weekly injections, and recently an oral administration has become available. Large‐scale randomized controlled cardiovascular (CV) outcome trials (CVOTs) have shown that GLP‐1RA therapy can reduce the risk of CV disease (CVD) in high‐risk individuals with T2D. In addition, GLP‐1RAs may have renal benefits driven by new‐onset macroalbuminuria, although no effect on hard renal endpoints has been found. Subsequently, the place for GLP‐1RA therapy has changed over recent years, with most societies endorsing GLP‐1RA therapy in patients with established or high risk of CVD independently of glycaemia. Initiation of GLP‐1RA therapy can be complex due to differences in efficacy, side effects and safety profiles as well as administration forms within the class. Implementing guideline recommendations into ideal patient selection may be challenging both in specialty and non‐specialty settings. To ensure adequate and proactive use of modern glucose‐lowering medications in the treatment of T2D, it is essential to recognize patients with high risk or documented CVD. The present review provides an overview of the efficacy and benefits of the currently available GLP‐1RA compounds. Furthermore, we review the results from recent large‐scale CVOTs in a clinical context and suggest improving the implementation of GLP‐1RA therapy across specialties to improve overall patient selection.

Effects of Glucagon-like Peptide-1 Receptor Agonists on Cardiovascular and Renal Outcomes: A Meta-Analysis and Meta-Regression Analysis

“…As for the other secondary outcomes, GLP-1RAs reduced composite renal outcome (HR: 0.80; 95% CI: 0.73–0.87; P < 0.001; I 2 = 45.0%) ( Figure 2 ), all-cause mortality (HR: 0.88; 95% CI: 0.82–0.94; P < 0.001; I 2 = 10.5%), hospitalization due to heart failure (HR: 0.89; 95% CI: 0.82–0.98; P = 0.013; I 2 = 2.5%), and renal function outcome (HR: 0.84; 95% CI: 0.73–0.97; P = 0.016; I 2 = 31.4%) ( Supplementary Figure 1 ).…”

“…Our meta-analysis reaffirms the cardiovascular and renal benefits of GLP-1RAs suggested by previous studies 29–31 and supports the current guidelines that recommend GLP-1RAs for the treatment of diabetes in individuals with established cardiovascular diseases or in those who are at high risk of cardiovascular diseases. 1, 2, 32, 33 In addition to the trials included in previous meta-analyses, our study also included AMPLITUDE-O, which is the latest trial using the GLP-1RA with the exendin backbone to show the successful reduction of MACE. By including AMPLITUDE-O, our meta-analysis increased the sample size by 4,076, providing more robust evidence on GLP-1RA efficacy.…”

“…While human GLP-1-based GLP-1RAs reduced MACE (HR: 0.84; 95% CI: 0.79–0.90; P < 0.001) with low heterogeneity ( I 2 = 0.0%, P = 0.513), exendin-based GLP-1RAs did not reduce MACE (HR: 0.90; 95% CI: 0.78–1.04; P = 0.163). The difference could be due to the large heterogeneity of exendin-based GLP-1 trials ( I 2 = 67.2%, P = 0.047). Individually, ELIXA was different from the other two trials (EXSCEL and AMPLITUDE-O) in terms of recruited individuals with a recent acute coronary syndrome.…”

“…Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown cardiovascular and renal benefits in cardiovascular outcome trials and played a key role in the management of type 2 diabetes. 1, 2…”

Personalized Type 2 Diabetes Management: An Update on Recent Advances and Recommendations

“…Therapies within the GLP-1RA and SGLT2i classes have the strongest evidence to support cardiovascular benefit in people with T2D. 32,33 34 However, this drug is not yet approved for use in T2D. Each of the dipeptidyl peptidase-IV (DPP-IV) inhibitors were not associated with cardiovascular harm.…”