DPP-4 inhibitors in the management of type 2 diabetes: a critical review of head-to-head trials

Diabetes Metab. 2012 Apr;38(2):89-101. doi: 10.1016/j.diabet.2011.11.001. Epub 2011 Dec 22.

Abstract

Dipeptidyl peptidase-4 (DPP-4) inhibitors offer new options for the management of type 2 diabetes. Direct comparisons with active glucose-lowering comparators in drug-naive patients have demonstrated that DPP-4 inhibitors exert slightly less pronounced HbA(1c) reduction than metformin (with the advantage of better gastrointestinal tolerability) and similar glucose-lowering effects as with a thiazolidinedione (TZD; with the advantage of no weight gain). In metformin-treated patients, gliptins were associated with similar HbA(1c) reductions compared with a sulphonylurea (SU; with the advantage of no weight gain, considerably fewer hypoglycaemic episodes and no need for titration) and a TZD (with the advantage of no weight gain and better overall tolerability). DPP-4 inhibitors also exert clinically relevant glucose-lowering effects compared with a placebo in patients treated with SU or TZD (of potential interest when metformin is either not tolerated or contraindicated), and as oral triple therapy with a good tolerability profile when added to a metformin-SU or pioglitazone-SU combination. Several clinical trials also showed a consistent reduction in HbA(1c) when DPP-4 inhibitors were added to basal insulin therapy, with no increased risk of hypoglycaemia. Because of the complex pathophysiology of type 2 diabetes and the complementary actions of glucose-lowering agents, initial combination of a DPP-4 inhibitor with either metformin or a glitazone may be applied in drug-naive patients, resulting in greater efficacy and similar safety compared with either drug as monotherapy. However, DPP-4 inhibitors were less effective than GLP-1 receptor agonists for reducing HbA(1c) and body weight, but offer the advantage of being easier to use (oral instead of injected administration) and lower in cost. Only one head-to-head trial demonstrated the non-inferiority of saxagliptin vs sitagliptin. Clearly, more trials of direct comparisons between different incretin-based therapies are needed. Because of their pharmacokinetic characteristics, pharmacodynamic properties (glucose-dependent glucose-lowering effect) and good overall tolerability profile, DPP-4 inhibitors may have a key role to play in patients with renal impairment and in the elderly. The role of DPP-4 inhibitors in the therapeutic armamentarium of type 2 diabetes is rapidly evolving as their potential strengths and weaknesses become better defined mainly through controlled clinical trials.

Publication types

  • Review

MeSH terms

  • Adamantane / analogs & derivatives
  • Adamantane / therapeutic use
  • Clinical Trials as Topic
  • Cost-Benefit Analysis
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dipeptides / therapeutic use
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
  • Drug Therapy, Combination
  • Female
  • Glycated Hemoglobin A / drug effects
  • Glycated Hemoglobin A / metabolism*
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Linagliptin
  • Male
  • Metformin / therapeutic use*
  • Nitriles / therapeutic use
  • Piperidines / therapeutic use
  • Purines / therapeutic use
  • Pyrazines / therapeutic use
  • Pyrrolidines / therapeutic use
  • Quinazolines / therapeutic use
  • Sitagliptin Phosphate
  • Triazoles / therapeutic use
  • Uracil / analogs & derivatives
  • Uracil / therapeutic use
  • Vildagliptin
  • Weight Gain / drug effects*

Substances

  • Dipeptides
  • Dipeptidyl-Peptidase IV Inhibitors
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Nitriles
  • Piperidines
  • Purines
  • Pyrazines
  • Pyrrolidines
  • Quinazolines
  • Triazoles
  • hemoglobin A1c protein, human
  • Linagliptin
  • Uracil
  • Metformin
  • saxagliptin
  • Vildagliptin
  • alogliptin
  • Adamantane
  • Sitagliptin Phosphate