While these data suggest the potential of small molecule GLP-1R PAMs for T2DM treatment, further optimization is still required towards a clinical candidate.
Whilst such effects of GIP antagonism are yet to be evaluated in humans, recent studies using combined GIP and GLP-1 agonists have shown weight reduction and improved glycaemic control in people with type 2 diabetes (T2D).
Next, we present the results from major randomized controlled trials on the use of GLP-1 receptor agonists for managing type 2 diabetes, and emerging data on treating obesity and prediabetes.
A randomized, double-blind, placebo-controlled, 4-week phase 1 multiple-ascending-dose study (NCT02411825) in 36 overweight to obese subjects with type 2 diabetes mellitus receiving SAR425899 demonstrated decreased body weight with a safety profile comparable with GLP-1R agonists.
Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are emerging as an important therapy to consider for patients with type 2 diabetes (T2D) given this class of treatment's ability to reduce glycated haemoglobin and their associated weight loss and low risk for hypoglycaemia.
Liraglutide is a GLP-1 receptor agonist recently approved for Type-II diabetes (T2D) treatment with superior hypoglycemic effect while also improving cardiovascular function for the patients.
Drugs acting as glucagon-like peptide-1 receptor agonists (GLP-1RAs) developed for the management of T2DM reduce body weight and liraglutide is the first GLP-1RA to be approved for the treatment of obesity in patients with and without T2DM.<b>Areas covered</b>: In this review of relevant published material, the authors summarize the pharmacokinetics, pharmacodynamics, clinical efficacy and safety of liraglutide for the treatment of obesity.<b>Expert opinion</b>: Liraglutide effectively reduces body weight and body fat through mechanisms involving reduced appetite and lowered energy intake, independent of its glucose-lowering effects.
PubMed, Embase, and the Cochrane Library were searched for randomized controlled trials (RCTs) comparing SGLT2is plus Dipeptidyl-Peptidase 4 inhibitors (SGLT2is/DPP4is) or glucagon like peptide-1 receptor agonists (SGLT2is/GLP-1RAs) against SGLT2is as monotherapy or add-on to metformin in T2DMs.
Nevertheless, prior animal and human studies on incretin mimetics, glucagon like peptide-1 receptor agonists (GLP-1 RA) approved for T2DM treatment, have provided indirect evidence that they may also ameliorate NAFLD/NASH, whereas dipeptidyl dipeptidase-4 inhibitors (DDP-4i) were not better than placebo in reducing liver fat in T2DM patients with NAFLD.
Cardiovascular outcome trials (eg, LEADER [Liraglutide Effect and Action in Diabetes Evaluation of Cardiovascular Outcome Results], SUSTAIN-6) demonstrated that GLP-1 (glucagon-like peptide 1) analogs including liraglutide reduce the risk of cardiovascular events in type 2 diabetes mellitus.
Trend 2010-2018 in the clinical use of GLP-1 receptor agonists for the treatment of type 2 diabetes in routine clinical practice: an observational study from Northeast Italy.
Insulin degludec/liraglutide (IDegLira) is a fixed-ratio combination (FRC) of basal insulin and glucagon-like protein-1 receptor agonist (GLP-1 RA) that has demonstrated glycemic and metabolic benefits in patients with type 2 diabetes mellitus (T2DM) in both randomized controlled trials and real-world studies.
This was a prospective cohort study that examined change in lung function measurements over two years of T2DM patients (n = 32) treated with metformin monotherapy (control cohort), metformin plus GLP-1R agonists (GLP-1R agonists cohort), or metformin plus insulin (insulin cohort).
Although none of the trials are fully representative of the general population, among the four trials examined, results from baseline REWIND were found to be more generalizable to the US adult T2D population than those of other GLP-1 RA CVOTs.
Following publication of the original article [1], based on the authors review, the GLP1 receptor agonists in type 2 diabetes published in Cardiovascular Diabetology, a meta-analysis of GLP-1 and non-GLP-1 based therapies was performed on cardiovascular outcomes.
Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) improve cardiovascular and renal outcomes in patients with type 2 diabetes through distinct mechanisms.
Safety and Pharmacokinetics of Single and Multiple Ascending Doses of the Novel Oral Human GLP-1 Analogue, Oral Semaglutide, in Healthy Subjects and Subjects with Type 2 Diabetes.
Altered GLP-1 secretion from L cells has been implicated in the development of type 2 diabetes mellitus and its resolution following bariatric surgery.