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

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-tohead 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. Keywords:Clinical trial-DPP-4 inhibitor; Alogliptin; Linagliptin; Saxagliptin; Sitagliptin; Vildagliptin; Type 2 diabetes mellitus; Review Résumé Les inhibiteurs de la DPP-4 dans le traitement du diabète de type 2 : revue critique des essais cliniques contrôlés.Les inhibiteurs de la dipeptidylpeptidase-4 (DPP-4) offrent de nouvelles options pour le traitement du diabète de type 2. Des comparaisons directes avec d'autres médicaments antidiabétiques chez des patients naïfs de tout traitement ont démontré que les inhibiteurs de la DPP-4 étaient un peu moins puissants pour diminuer ...

Dipeptidyl peptidase 4 inhibitors in routine clinical practice: experiences from a Scottish teaching hospital

“…One hundred and thirty-three (69.3%) exhibited a reduction in HbA1c of >5mmol/mol which indicates a successful response to DPP4i therapy according to national prescribing guidance. 3,7 Comparison of HbA1c concentration at initiation and glycaemic response to DDP4i initiation, where DPP4i initiation was the only therapeutic intervention, can be seen in Figure 1. Patients in the higher groupings of initial HbA1c appeared to have a larger glycaemic response to therapy.…”

“…Treatment should be continued only if a successful glycaemic response is observed at 3-6 months (>5.5mmol/mol reduction in HbA1c). 3,7 Clinical trial evidence for glycaemic and weight effects of DPP4i are readily available, but there is a lack of observational data pertaining to the "real-life" practical use of these drugs and their effect on glycaemic and weight control. This study assessed the impact of these drugs on glycaemic control and weight of patients attending the Diabetes Centre, Gartnavel General Hospital, Glasgow, UK.…”

GLP-1 receptor agonists or DPP-4 inhibitors: How to guide the clinician?

“…16 Il y a très peu d'essais cliniques qui ont comparé directement un inhibiteur de la DPP-4 (par ailleurs tous réalisés avec la sitagliptine) avec un agoniste des récepteurs du GLP-1. 6,50 Les principaux résultats sont rassemblés dans le tableau 2. [51][52][53][54][55][56] Ils confirment les comparaisons indirectes rassemblées dans les méta-analyses avec une réduction plus importante du taux d'HbA1c, de la glycémie à jeun et du poids corporel avec les agonistes du GLP-1 par comparaison avec la sitagliptine 100 mg; par contre, les différences en termes de variations de pression artérielle ne sont pas consistantes d'un essai à l'autre.…”

Efficacy and safety of Jentadueto® (linagliptin plus metformin)

“…However, the positioning of DPP-4 inhibitors in the management of T2DM, especially their place compared with sulfonylureas after metformin failure [10][11][12] , is still a matter of debate.…”