Uncertainties around incretin-based therapies: A literature review

Abstract

Diabetes mellitus is a chronic debilitating and non-communicable disease. It has several long-term outcomes that are associated with various end organ damage, mainly the heart, blood vessels, eyes, nerves, and kidneys. There are different modalities of treatment of diabetes. The recent incretin-based therapies provided an innovative class of drugs including GLP-1 receptor agonists and DPP-4 inhibitors. This review aims to summarize the available evidence of their effectiveness. This is a narrative review. Several databases were searched. Search terms used were MeSH and keywords with different combinations of Boolean operators according to the database but were comparable. Studies included were: randomized controlled trials, cohort and case-controlled studies, health technology report, meta-analysis, and systematic reviews. Results were analysed and reported in a narrative style with emphasis on the effectiveness and adverse effects of various types of incretin based therapies. 17 articles were retrieved as they fulfilled the inclusion criteria. They were heterogeneous in terms of interventions, participants, settings and outcomes. Studies varied in their quality and/or reporting of their findings conducted in several settings. There are two types of incretin: Glucose dependent Insulinotropic Peptide (GIP) and Glucagon-like Peptide 1 (GLP-1). There is no question that incretin-based glucose-lowering medications have demonstrated to be effective glucose-lowering drugs. They proved an evidence-based efficacy profile and appear to do so with significant effects to stimulate weight loss with minimal hypoglycaemia. However, there are few side effects that should not be overlooked when deciding to use such therapies. The findings of our review presented here, do not prove that these agents are unsafe, but it does suggest that the burden of evidence now rests with those who hope to persuade us of their safety. Continuous clinical monitoring and more research are essential to clarify the actions of GLP-1R agonists and DPP-4 on the normal and diabetic exocrine pancreas.

The role of novel antihyperglycaemic agents in the treatment of Type 2 diabetes: From glycaemic control to cardiovascular protection

“…Possible explanations for the positive cardiovascular effects of GLP-1 receptor agonists are based on the findings that stimulation of the GLP-1 receptor in the heart leads to increased NO production, increased glucose uptake into cardiomyocytes, and improved coronary flow. The positive effect of GLP-1 receptor stimulation on suppression of atherosclerosis has been demonstrated (50). Activation of the GLP-1 receptor in the central nervous system is considered to be responsible for the effects this group of drugs has on reducing appetite and increasing the feeling of satiety, delaying gastric emptying, but also on side effects such as nausea (48).…”

Polyalthia Clerodane Diterpene Potentiates Hypoglycemia via Inhibition of Dipeptidyl Peptidase 4

“…Currently, synthetic DPP-4 inhibitors like sitagliptin and vildagliptin have clinically been used to treat TII DM. Interestingly, researchers have also reviewed current DPP-4 inhibitors as interacting with diuretics, warfarin, digoxin, and monoamine oxidase inhibitors, which alters DPP-4 metabolism or vice versa [10]. However, all synthetic DDP-4 compounds may occasionally contain adverse- or side-effects, and herbal medicines are believed to have lower adverse effects with similar efficacy [11].…”