Glucagon like peptide-1 receptor agonist (GLP-1RA) therapy in management of type 2 diabetes: choosing the right agent for individualised care

Abstract

Glucagon like peptide-1 receptor agonists (GLP-1RAs) are a new class of injectable agent used in the management of type 2 diabetes (T2DM). In the UK, NICE approved the use of GLP-1RAs in combination with metformin and sulphonylurea in people with T2DM whose glycaemic control is above target (≥7.5%, 58 mmol/mol) and body mass index (BMI) ≥35 kg/m 2 with other medical problems associated with obesity or for whom insulin therapy would have significant occupational implications or weight loss would benefit other significant obesityrelated comorbidities in people with BMI <35 kg/m 2 . Unlike many other classes of glucose lowering agents, GLP-1RAs not only improve glycaemic control but also promote weight loss with a low risk of hypoglycaemia. In randomised controlled trials, treatment with GLP-1RAs either as monotherapy or in combination with oral hypoglycaemic agents or insulin, has demonstrated significant improvement in glycaemic control by 1-2% with weight loss of approximately 1-5 kg. In addition, they exert a positive effect on cardio-metabolic risk factors by reducing body weight, lowering blood pressure and improving the lipid profile. Gastrointestinal side effects are the most common adverse events with GLP-1RA therapy. Since the first GLP-1RA was approved in 2005, a number of other GLP-1RAs are now available. However, their glycaemic efficacy, safety profiles and mode of delivery differ, and this review article aims to give an overview of differences among GLP-1RAs and to provide decision makers with an overview of the evidence when choosing a particular GLP-1RA for individualised therapy. Br J Diabetes 2016;16:128-137

Glucagon-Like Peptide-1 Receptor Agonists in Patients with Type 2 Diabetes: Prescription According to Reimbursement Constraints and Guideline Recommendations in Catalonia

“…The experience regarding long-term safety and effectiveness of GLP-1RAs is limited because they were marketed only about ten years ago, and the cost of this class of drugs is substantial compared to other agents [20]. For these reasons, guidelines from some European countries, including the United Kingdom (National Institute for Health and Clinical Excellence—NICE) and Catalonia (Catalan Health Service—CatSalut), recommend to discontinue treatment if no beneficial response (defined as a reduction of at least 1.0 percentage point in HbA1c [11 mmol/mol] and 3% in initial weight) has been observed after six months of therapy initiation [21,22].…”

Glycaemic and non‐glycaemic efficacy of once‐weekly GLP‐1 receptor agonists in people with type 2 diabetes

“…QW GLP‐1 RAs have also been shown to attenuate post‐prandial glucose (PPG) excursions, with the greatest reductions observed for treatment with semaglutide 1 mg over either dulaglutide 1.5 mg or exenatide ER 2 mg 39,40 . Previously, it has been noted by Htike et al that greater PPG reductions have been associated with shorter‐ versus longer‐acting GLP‐1 RA formulations, 42 though this is primarily true for the meal immediately following administration of the last dose 43 . PPG excursions have not been consistently reported across all trials 36‐40 but may have clinically important implications 15,35,44,45 .…”

Efficacy and Safety of Dulaglutide Monotherapy Compared to Glimepiride in Oral Antihyperglycemic Medication-Naïve Chinese patients with Type 2 Diabetes: A Post Hoc Analysis of AWARD-CHN1

“…GLP-1 receptor agonists can also improve beta cell function, as assessed by homeostatic model assessment (HOMA)-B analysis and proinsulinto-insulin ratio, and markedly improve firstand second-phase insulin responses, and are able to restore beta cell sensitivity to glucose [3]. Additionally, GLP-1 receptor agonists are effective glucose-lowering agents associated with weight loss, cardiovascular benefits, and low risk of hypoglycemia, providing advantages over sulfonylureas, which are associated with hypoglycemia and weight gain, but are still widely used across East Asia [6][7][8].…”