Introduction Diabetes mellitus is a chronic debilitating and non communicable

Introduction
Diabetes mellitus is a chronic debilitating and non-communicable disease characterized by chronic hyperglycaemia and resulting from a defect in carnosic acid secretion, insulin action, or both (Alberti and Zimmet, 1998; American Diabetes Association, 2011). It has several long-term outcomes that are associated with various end organ damage, mainly the heart, blood vessels, eyes, nerves, and kidneys (ADA, 2010). Furthermore, diabetes estimated to cost the government of Saudi Arabia about $1.87 billion annually (Almalki et al., 2011).
The number of people with diabetes in 2012 has been estimated to be 381.8 million worldwide with an anticipated increase of 55% to 591.9 million by 2035 (Guariguata et al., 2014). In Saudi Arabia, the estimated prevalence of diabetes in 2011 is 16.2% and estimated to be 20.8% in 2030 (Whiting et al., 2011). There remain large variations in the burden of diabetes across countries and income groups.
Although the number of patients with diabetes that successfully achieve target levels of A1C is gradually improving, a considerable number of subjects continue to fall short of satisfactory treatment goals, leaving them at high risk for the development of diabetes-associated complications (Hoerger et al., 2008). Suggested initial therapy generally includes lifestyle management and patient education joined with metformin therapy. Although metformin is widely accepted as the preferred medication for the initial treatment of type 2 diabetes (T2DM), there is still a considerable uncertainty and lack of consensus regarding the choice of additional agents that need to be added to metformin to optimize glycaemic control (Drucker et al., 2010). Other oral hypoglycaemic agents included also Sulphonylureas such as glipizide, glimepiride, and glyburide that induce the increased secretion of insulin. Moreover, insulin, as injection, might be introduced in the early stage of diabetes, depending on the number of risk factors the patients may have and the progression/deterioration of the diabetic stage.
Various drawbacks are associated with the previously discussed available medications. Amongst the concerns attributed to the available anti-diabetic medications are that they do not stop the progressive loss of β cell function, hence, ultimately they decreased their efficacy and necessitating the need for exogenous insulin injections (Amori et al., 2007). Most of the available therapies except metformin are associated with weight gain and this is disappointing since we know the strong relationship between obesity and type 2 diabetes (Verspohl, 2009). Studies in Canada show that nearly half of all patients with T2DM and who are under medication do not attain the recommended HbA1c levels of ⩽7% (Canadian Diabetes Association, 2008).
Recent developments in the treatment of diabetes have provided additional options for the control of diabetes mellitus. Incretin-based therapies are one of the breakthroughs that stimulate insulin secretion and reduce glucagon secretion, resulting in reduction of hepatic glucose production (Perfetti et al., 2000; Tourrel et al., 2001; Hui et al., 2003). There are two classes of drugs based on the incretin system: GLP-1 receptor agonist, such as exenatide and liraglutide and DPP-4 inhibitors that delay endogenous degradation of GLP-1 inhibiting DPP-4 (Triplitt et al., 2007). There are world-wide uncertainties and controversies regarding the use of such therapies. Therefore, the aim of the review is to summarize an updated evidence of the effectiveness and safety of incretin-based agents.

Review question

Method
We searched five databases including the following: the Cochrane library, MEDLINE, EMBASE, TRIP, and Science direct. We also searched databases of ongoing trials (clinicalTrials.gov/ and controlled-trials.com). Furthermore, we looked for other potentially eligible trials or ancillary publications by searching the reference lists of retrieved included trials, (systematic) reviews, meta-analyses and health technology assessment reports.