What have we learnt from “real world” data, observational studies and meta‐analyses

Abstract

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. Real world data are collected outside the controlled restrictions of RCTs and are therefore more representative of usual clinical practice. 3 Specific differences that can be identified include the fact that there is a clear sequence of outcomes with RCT and a wider range of outcomes with real world studies, follow-up is longer with real world studies and in general they are cheaper to conduct compared with RCTs. RCTs are often highly selective and exclude elderly patients (65 years and older), those with co-morbidities or taking other drugs whereas in real world practice, patients are often older than 65 years, suffer from multiple diseases and take several drugs and can be classified as " diverse and complex." 4 This review will consider what has been learnt from these two important but different sources of evidence for determining the place of incretin therapies in current type 2 diabetes management. and GIP by preventing rapid enzymatic degradation following secretion.Due to the glucose-dependent mechanism of action, these agents are 3 | HIERARCHY OF EVIDENCE | Clinical research trialsA RCT is considered the gold standard when assessing new interventions and therefore systematic reviews and meta-analyses with homogeneity of RCT are the highest level of evidence. Real-world data and observational studies provide important clinical data and outcomes beyond that gained from RCT and help us to understand the true impact of the intervention including its effectiveness, costeffectiveness and adverse effects ( Figure 1). Whereas RCT answer the question "can it work?" real world data are more concerned with answering "does it work?" 12 The primary focus of RCTs is efficacy, safety, quality and cost-effectiveness. Real world studies extend this to assess effectiveness, safety, quality, cost-effectiveness, natural history, compliance and adherence as we...

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