The Place of Dipeptidyl Peptidase-4 Inhibitors in Type 2 Diabetes Therapeutics: A “Me Too” or “the Special One” Antidiabetic Class?

Abstract

Incretin-based therapies, the most recent therapeutic options for type 2 diabetes mellitus (T2DM) management, can modify various elements of the disease, including hypersecretion of glucagon, abnormal gastric emptying, postprandial hyperglycaemia, and, possibly, pancreatic β cell dysfunction. Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) increase glucagon-like peptide-1 (GLP-1) availability and correct the “incretin defect” seen in T2DM patients. Clinical studies have shown good glycaemic control with minimal risk of hypoglycaemia or any other adverse effects, despite the reports of pancreatitis, whose association remains to be proved. Recent studies have been focusing on the putative ability of DPP-4 inhibitors to preserve pancreas function, in particular due to the inhibition of apoptotic pathways and stimulation of β cell proliferation. In addition, other cytoprotective effects on other organs/tissues that are involved in serious T2DM complications, including the heart, kidney, and retina, have been increasingly reported. This review outlines the therapeutic potential of DPP-4 inhibitors for the treatment of T2DM, focusing on their main features, clinical applications, and risks, and discusses the major challenges for the future, in particular the possibility of becoming the preferred therapy for T2DM due to their ability to modify the natural history of the disease and ameliorate nephropathy, retinopathy, and cardiovascular complications.

In vitro evidence for gut hormone stimulation release and dipeptidyl-peptidase IV inhibitory activity of protein hydrolysate obtained from cuttlefish ( Sepia officinalis ) viscera

“…In this way, incretin-based therapies based on the oral administration of DPP-IV inhibitors (gliptins) are the most recent alternative treatments of T2DM as recently reviewed (Godinho et al, 2015). Nowadays, numerous works have focused on the strategy to identify "natural" peptide inhibitors of DPP-IV activity as an alternative for synthetic drugs to restore the incretin effect in T2DM.…”

Postprandial dysmetabolism: Too early or too late?

“…They have no effect on body weight and they are safe with respect to causing hypoglycemia. 151 The various DPP4 inhibitors are similar concerning their antihyperglycemic properties. 151 Regarding the effectiveness of DPP4 in reducing postprandial hyperglycemia compared to other hypoglycemic agents targeting postprandial glucose, a recent study in 19 type 2 diabetics inadequately controlled by diet and exercise indicated that the effects of sitagliptin on postprandial glucose levels were similar to those of nateglinide.…”

“…151 The various DPP4 inhibitors are similar concerning their antihyperglycemic properties. 151 Regarding the effectiveness of DPP4 in reducing postprandial hyperglycemia compared to other hypoglycemic agents targeting postprandial glucose, a recent study in 19 type 2 diabetics inadequately controlled by diet and exercise indicated that the effects of sitagliptin on postprandial glucose levels were similar to those of nateglinide. 152 Pramlitidine is a synthetic analog of amylin which may be used with mealtime insulin in type 1 and type 2 diabetic patients.…”

GLP-1 receptor agonists, carotid atherosclerosis and retinopathy

“…An intensive glycemic control led to reduced microvascular complications, especially retinopathy and nephropathy, but had only a modest effect on macrovascular complications [3]. However, in addition to effects on pancreas function, the effects on other organs/tissues that are involved in T2DM complications, such as heart, kidney, and retina, have been increasingly reported [4]. It has become clear that in subjects with diabetes not only dysglycemia should be treated but also macrovascular and microvascular complications should be prevented and cared for.…”