Dipeptidyl peptidase-4 inhibitors and the management of type 2 diabetes mellitus

  title={Dipeptidyl peptidase-4 inhibitors and the management of type 2 diabetes mellitus},
  author={Julio Rosenstock and Bernard Zinman},
  journal={Current Opinion in Endocrinology, Diabetes and Obesity},
  • J. RosenstockB. Zinman
  • Published 1 April 2007
  • Medicine, Biology
  • Current Opinion in Endocrinology, Diabetes and Obesity
Purpose of reviewTo review recent clinical trials of oral dipeptidyl peptidase-4 inhibitors and examine their role in managing type 2 diabetes mellitus. Recent findingsOral dipeptidyl peptidase-4 inhibitors improve islet function by increasing α-cell and β-cell responsiveness to glucose, resulting in improved glucose-dependent insulin secretion and reduced inappropriate glucagon secretion. These agents appear to have physiologically based antihyperglycemic effects and may modify the progressive… 

Dipeptidyl Peptidase Inhibitors: A New Step Towards Normoglycemia

DPP-4 inhibitors seem to represent an efficient and well-tolerated new class of oral normoglycaemic agents, with a potential beneficial effect on pancreatic function, but their real efficacy and safety have to be firmly assessed in the future, before they could find their appropriate place in the management of type 2 diabetes.


Inhibition of dipeptidyl peptidase 4 is a promising new approach for the treatment of type 2 diabetes, and research has demonstrated that DPP-4 inhibitors portray a very low risk of hypoglycemia development.

Pharmacology of Dipeptidyl Peptidase-4 Inhibitors

A comprehensive and updated comparison of the pharmacodynamic and pharmacokinetic properties of DPP-4 inhibitors is provided, and pharmacological differences of potential interest for their use in therapy are pinpointed.

Sitagliptin: A Review of Its Use in Patients with Type 2 Diabetes Mellitus

Oral sitagliptin was generally well tolerated in clinical trials, had a low risk of hypoglycaemia, and had a neutral effect on body weight and there is little evidence that these drugs could cause pancreatic inflammation or pancreatic cancer.

Clinical overview of saxagliptin for Type 2 diabetes management

  • J. Rosenstock
  • Medicine
    Expert review of endocrinology & metabolism
  • 2010
Saxagliptin is generally well tolerated with weight-neutral effects and a low incidence of hypoglycemia and is indicated as an adjunct to diet and exercise alone, or in combination with metformin, a thiazolidinedione or a sulfonylurea to improve glycemic control in adults with Type 2 diabetes mellitus.

Alogliptin: a review of its use in the management of type 2 diabetes mellitus.

Oral alogliptin as monotherapy or in combination with other oral antihyperglycaemic agents or insulin therapy improved glycaemic control and was generally well tolerated in adult patients with inadequately controlled type 2 diabetes, including elderly patients.

Safety and Efficacy of Dulaglutide, a Once Weekly GLP-1 Receptor Agonist, for the Management of Type 2 Diabetes

Once-weekly dulaglutide should be a relevant additional treatment option for the management of T2D based on results of 3 phase 3 registration trials, which demonstrated superior efficacy at the primary endpoint to metformin as monotherapy, to sitagliptin as add-on to meetformin and pioglitazone.

Renoprotective Effects of the Dipeptidyl Peptidase-4 Inhibitor Sitagliptin: A Review in Type 2 Diabetes

This review aims to provide an overview of the current knowledge in the field of renoprotective actions of sitagliptin, namely, improvement in diabetic dysmetabolism, hemodynamic factors, renal function, diabetic kidney lesions, and cytoprotective properties.

Sitagliptin: a review of its use in the management of type 2 diabetes mellitus.

Current evidence suggests that sitagliptin is a useful treatment option for patients with type 2 diabetes, with potential advantages including oral administration, a generally weight-neutral effect and a low risk of hypoglycaemia.

Incretin-based therapies for treatment of postprandial dyslipidemia in insulin-resistant states

Evidence supporting a beneficial effect of incretin-based therapies on diabetic dyslipidemia through modulation of intestinal lipoprotein metabolism is summarized, as this offers a major new therapeutic approach to reduce cardiovascular risk in type 2 diabetic patients.



Incretin mimetics and dipeptidyl peptidase-IV inhibitors: a review of emerging therapies for type 2 diabetes.

Novel therapies that leverage the so-called "incretin effect" of GLP-1 (including the incretin mimetics and dipeptidyl peptidase-IV (DPP-IV) inhibitors) are being actively developed for the management of type 2 diabetes.

Inhibitors of dipeptidyl peptidase IV: a novel approach for the prevention and treatment of Type 2 diabetes?

Inhibitors of the enzyme dipeptidyl peptidase IV (DPP IV) are of increasing interest to both diabetologists and the pharmaceutical industry alike, as they may become established as the next member of

Chronic Inhibition of Dipeptidyl Peptidase-4 With a Sitagliptin Analog Preserves Pancreatic β-Cell Mass and Function in a Rodent Model of Type 2 Diabetes

Treatment of mice with des-fluoro-sitagliptin, but not glipizide, significantly increased islet insulin content and improved glucose-stimulated insulin secretion in isolated islets suggest that DPP-4 inhibitors may offer long-lasting efficacy in the treatment of type 2 diabetes by modifying the courses of the disease.

Vildagliptin, a dipeptidyl peptidase-IV inhibitor, improves model-assessed beta-cell function in patients with type 2 diabetes.

Vildagliptin is an incretin degradation inhibitor that improves beta-cell function in diabetic patients by increasing the insulin secretory tone.

Vildagliptin: an inhibitor of dipeptidyl peptidase-4 with antidiabetic properties

  • B. Ahrén
  • Biology, Medicine
    Expert opinion on investigational drugs
  • 2006
In clinical trials, vildagliptin improves glycaemic control both as monotherapy and in combination with metformin for periods of ≤ 52 weeks in subjects with Type 2 diabetes, and has proven to be safe and tolerable, with a low occurrence of hypoglycaemia.

DPP‐4 inhibitors and their potential role in the management of type 2 diabetes

  • A. Barnett
  • Medicine, Biology
    International journal of clinical practice
  • 2006
The leading DPP‐4 inhibitors have shown clinically significant HbA1c reductions up to 1 year of treatment and offer many potential advantages over existing diabetes therapies including a low risk of hypoglycaemia, no effect on body weight, and the potential for the regeneration and differentiation of pancreatic β‐cells.

Inhibition of dipeptidyl peptidase-4 reduces glycemia, sustains insulin levels, and reduces glucagon levels in type 2 diabetes.

Improved metabolic control by DPP-4 inhibition in type 2 diabetes is seen in association with reduced glucagon levels and, despite the lower glycemia, unaltered insulin levels.

Effect of single oral doses of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on incretin and plasma glucose levels after an oral glucose tolerance test in patients with type 2 diabetes.

In patients with type 2 diabetes, near maximal glucose-lowering efficacy of sitagliptin after single oral doses was associated with inhibition of plasma DPP-4 activity of 80% or greater, corresponding to a plasma sitgliptin concentration of 100 nm or greater and an augmentation of active GLP-1 and GIP levels of 2-fold or higher after an OGTT.

Enhancing incretin action for the treatment of type 2 diabetes.

The need for daily injections of potentially immunogenic GLP-1-derived peptides and the potential for unanticipated side effects with chronic use of DPP-IV inhibitors will require ongoing scrutiny of the risk-benefit ratio for these new therapies as they are evaluated in the clinic.

Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy in patients with type 2 diabetes mellitus

Sitagliptin significantly improved glycaemia control and was well tolerated in patients with type 2 diabetes mellitus who had inadequate glycaemic control on exercise and diet.