Glycaemic efficacy of glucagon‐like peptide‐1 receptor agonists and dipeptidyl peptidase‐4 inhibitors as add‐on therapy to metformin in subjects with type 2 diabetes—a review and meta analysis

  title={Glycaemic efficacy of glucagon‐like peptide‐1 receptor agonists and dipeptidyl peptidase‐4 inhibitors as add‐on therapy to metformin in subjects with type 2 diabetes—a review and meta analysis},
  author={Carolyn F. Deacon and Edoardo Mannucci and Bo Ahr{\'e}n},
Aims: During recent years, two strategies of incretin‐based therapy [glucagon‐like peptide‐1 (GLP‐1) receptor agonism and dipeptidyl peptidase‐4 (DPP‐4) inhibition] have entered the market for pharmacological management of type 2 diabetes. A main indication for this therapy is as add‐on to on‐going metformin therapy in subjects with type 2 diabetes who have insufficient glycaemic control with metformin alone. The aim of this study was to compare improvements in glycaemic control and changes in… 

Combination therapy of dipeptidyl peptidase‐4 inhibitors and metformin in type 2 diabetes: rationale and evidence

  • Y. LiuT. Hong
  • Medicine, Biology
    Diabetes, obesity & metabolism
  • 2014
The combination of DPP‐4 inhibitors and metformin provides an additive or even synergistic effect on metabolic control in patients with T2DM.

Defining the role of GLP-1 receptor agonists for individualized treatment of Type 2 diabetes

  • D. YabeY. Seino
  • Biology, Medicine
    Expert review of endocrinology & metabolism
  • 2014
This review focuses on the use ofGLP-1 RAs in the treatment of T2DM, with reference to the differing dominant mechanisms of action between short- and long-acting GLP- 1 RAs and the clinical implications of this difference.

Lixisenatide as add‐on to oral anti‐diabetic therapy: an effective treatment for glycaemic control with body weight benefits in type 2 diabetes

Five phase III studies in the GetGoal clinical trial programme assessed the efficacy of lixisenatide, a once‐daily prandial glucagon‐like peptide‐1 receptor agonist, in combination with oral anti‐diabetics in patients with T2DM insufficiently controlled using oral anti-diabetic drugs.

Is there a place for incretin therapies in obesity and prediabetes?

Incretin therapy for type 2 diabetes: GLP-1 receptor agonists and DPP-4 inhibitors

In conclusion, incretin therapy is safe with very few adverse events and an additional value of the therapy is a very low risk for hypoglycaemia.

Gastrointestinal actions of glucagon‐like peptide‐1‐based therapies: glycaemic control beyond the pancreas

Understanding pharmacokinetic and pharmacodynamic differences in GLP‐1 receptor agonists may allow personalized antihyperglycaemic therapy in type 2 diabetes, and provide the rationale to explore treatment in patients with no or little residual β‐cell function.

Feedback suppression of meal‐induced glucagon‐like peptide‐1 (GLP‐1) secretion mediated through elevations in intact GLP‐1 caused by dipeptidyl peptidase‐4 inhibition: a randomized, prospective comparison of sitagliptin and vildagliptin treatment

To compare directly the clinical effects of vildagliptin and sitagliptin in patients with type 2 diabetes, with a special emphasis on incretin hormones and L‐cell feedback inhibition induced by

Combination therapy of SGLT2 inhibitors with incretin-based therapies for the treatment of type 2 diabetes mellitus: Effects and mechanisms of action

The mechanisms of action, glycemic and cardiovascular effects of SGLT2 inhibitors and incretin-based therapies and their combination in the treatment of T2DM are reviewed.

Cost–Utility Analysis of Glucagon-Like Peptide-1 Agonists Compared with Dipeptidyl Peptidase-4 Inhibitors or Neutral Protamine Hagedorn Basal Insulin as Add-On to Metformin in Type 2 Diabetes in Sweden

Treatment strategy with GLP-1 agonists is a cost-effective strategy in comparison to DPP-4 inhibitors and NPH insulin among T2DM patients inadequately controlled with metformin alone in a Swedish setting.



Dipeptidyl Peptidase‐4 Inhibitors Administered in Combination With Metformin Result in an Additive Increase in the Plasma Concentration of Active GLP‐1

The study results show that metformin is not a DPP‐4 inhibitor but rather enhances precursor GCG expression in the large intestine, resulting in increased total GLP‐1 concentrations, which have complementary mechanisms of action and additive effects with respect to increasing the concentrations of active GLP-1 in plasma.

Incretin‐based therapies – review of the physiology, pharmacology and emerging clinical experience

In this review, aspects of incretin biology and pharmacotherapy are addressed with a view to highlighting potentially clinically relevant issues and areas of basic research that may impinge on these.

Incretin based therapies for type 2 diabetes mellitus.

Therapeutic approaches for enhancing the incretin action include degradation resistant GLP-1 receptor agonists (incretin mimetics) and inhibitors of dipeptidyl peptidase-IV (DLP-IV) activity (Incretin enhancers- gliptins).

Efficacy and safety of adding the dipeptidyl peptidase‐4 inhibitor alogliptin to metformin therapy in patients with type 2 diabetes inadequately controlled with metformin monotherapy: a multicentre, randomised, double‐blind, placebo‐controlled study

Aims:  To evaluate the efficacy and safety of alogliptin, a new dipeptidyl peptidase‐4 inhibitor, for 26 weeks at once‐daily doses of 12.5 and 25 mg in combination with metformin in patients whose

Efficacy and safety of saxagliptin in combination with metformin compared with sitagliptin in combination with metformin in adult patients with type 2 diabetes mellitus

This 18‐week, phase 3b, multicentre, double‐blind, noninferiority trial compared the efficacy and safety of two dipeptidyl peptidase‐4 inhibitors, saxagli leptin and sitagliptin, in patients whose glycaemia was inadequately controlled with metformin.

Novel combination treatment of type 2 diabetes DPP-4 inhibition + metformin

  • B. Ahrén
  • Medicine
    Vascular health and risk management
  • 2008
Both fasting and prandial glucose are reduced by DPP-4 inhibition in combination with metformin in association with improvement of insulin secretion and insulin resistance and increase in concentrations of active GLP-1.

Efficacy and Safety of Long-Acting Glucagon-Like Peptide-1 Receptor Agonists Compared with Exenatide Twice Daily and Sitagliptin in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis

Compared with other incretin-based therapies, LA-GLP-1RAs produce greater improvement in A1C and FPG and result in a potentially favorable adverse event profile compared with exenatide twice daily.

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.

Use of DPP-4 inhibitors in type 2 diabetes: focus on sitagliptin

  • B. Ahrén
  • Medicine, Biology
    Diabetes, metabolic syndrome and obesity : targets and therapy
  • 2010
Sitagliptin has in several clinical studies been shown to improve metabolic control in type 2 diabetes, both when used as monotherapy and when used in combination with metformin, sulfonylurea, thiazolidinediones or insulin.