Novel combination treatment of type 2 diabetes DPP-4 inhibition + metformin.
Inhibition of dipeptidyl peptidase-4 (DPP-4) as a novel therapy for type 2 diabetes is based on prevention of the inactivation process of bioactive peptides, the most important in the context of treatment of diabetes of which is glucagon-like peptide-1 (GLP-1). Most clinical experience with DPP-4 inhibition is based on vildagliptin (GalvusR, Novartis) and sitagliptin (JanuviaR, Merck). These compounds improve glycemic control both in monotherapy and in combination with other oral hyperglycemic agents. Both have also been shown to efficiently improve glycemic control when added to ongoing metformin therapy in patients with inadequate glycemic control. Under that condition, they reduce HbA1C levels by 0.65%-1.1% (baseline HbA1C 7.2-8.7%) in studies up to 52 weeks of duration in combination versus continuous therapy with metformin alone. Sitagliptin has also been examined in initial combination therapy with metformin have; HbA1 was reduced by this combination by 2.1% (baseline HbA1C 8.8%) after 24 weeks of treatment. 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. The combination of DPP-4 inhibition and metformin has been shown to be highly tolerable with very low risk of hypoglycemia. Hence, DPP-4 inhibition in combination with metformin is an efficient, safe and tolerable combination therapy for type 2 diabetes.
Department of Clinical Sciences, Division of Medicine, Lund University, Lund, Sweden. bo.ahren@med.lu.se
Bo
B
Ahrén
D000218:Adamantane / Q000031:analogs & derivatives / Q000627:therapeutic use; D001786:Blood Glucose / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000201:enzymology; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D008687:Metformin / Q000627:therapeutic use*; D009570:Nitriles / Q000627:therapeutic use; D011719:Pyrazines / Q000627:therapeutic use; D011759:Pyrrolidines / Q000627:therapeutic use; D000068900:Sitagliptin Phosphate; D013997:Time Factors; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use; D000077597:Vildagliptin
D000218:Adamantane; D001786:Blood Glucose; D018819:Dipeptidyl Peptidase 4; D054873:Dipeptidyl-Peptidase IV Inhibitors; D052216:Glucagon-Like Peptide 1; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin; D009570:Nitriles; D011719:Pyrazines; D011759:Pyrrolidines; D000068900:Sitagliptin Phosphate; D014230:Triazoles; D000077597:Vildagliptin; C517652:hemoglobin A1c protein, human; C042807:DPP4 protein, human