What have we learnt from "real world" data, observational studies and meta-analyses.

The incretin therapies glucagon-like peptide-1 receptor agonists (GLP-1 RA) and dipeptidyl peptidase-IV (DPP-IV) inhibitors are now well-established as second and third-line therapies and in combination with insulin for the treatment of type 2 diabetes. Over the last decade, there is accumulating evidence of their efficacy and safety from both large multicentre randomized clinical trials (RCT) and observational studies. Cardiovascular outcome trials have confirmed that several of these agents are also non-inferior to placebo with the GLP-1 RA liraglutide and semaglutide recently found to be superior in terms of major adverse cardiovascular events. Observational studies and post-marketing surveillance provide real world evidence of safety and effectiveness of these agents and have provided reassurance that signals for pancreatitis and pancreatic cancer seen in clinical trials are not of major concern in large patient populations. Well-designed real world studies complement RCTs and systematic reviews but appropriate data and methodologies, which are constantly improving, are necessary to answer appropriate clinical questions relating to the use of incretin therapies.