Managing hyperglycemia in patients with type 2 diabetes mellitus: rationale for the use of dipeptidyl peptidase-4 inhibitors in combination with other oral antidiabetic drugs.
OBJECTIVE
Type 2 diabetes mellitus is a chronic, progressive disease that necessitates comprehensive and individualized patient treatment strategies. Daily glycemic measures, including measures of postprandial glucose and fasting plasma glucose levels, in combination with measures of glycated hemoglobin (HbA(1c)) levels may be a more reliable indicator of blood glucose control and the long-term risk of complications than measures of HbA(1c) levels alone. Emerging treatment strategies for type 2 diabetes support the rationale for using dipeptidyl peptidase-4 (DPP-4) inhibitors in combination with other oral antidiabetic drugs for early and aggressive management of type 2 diabetes.


METHODS
Information was gathered through a search of MEDLINE, Derwent Drug File, BIOSIS, and EMBASE databases for DPP-4 inhibitors and postprandial hyperglycemia in patients with type 2 diabetes.


METHODS
Studies published from 2003 to the present and in any language were included. Additional sources were relevant conference poster presentations.


RESULTS
Early in the disease process, more intensive glucose-lowering intervention prior to the onset of advanced disease and cardiovascular events may be necessary to demonstrate effective reduction in macrovascular risk. Recent advances in pharmacotherapy allow physicians to target glucose excursions and variability. Data support the use of a combination of drugs with a complementary mechanism of action; to achieve an HbA(1c) level of less than 7% of total hemoglobin, use a drug with a primary mechanism of action that targets postprandial glucose levels in combination with a drug that primarily lowers fasting plasma glucose levels. Based on the glucose-dependent action of incretins, DPP-4 inhibitors demonstrate a low propensity for hypoglycemia, are generally weight neutral, and have a low risk of interactions with other drugs, which makes them appropriate candidates for combination therapy, particularly with other oral antidiabetic drugs including metformin, thiazolidinediones, and sulfonylureas.


CONCLUSIONS
The complementary mechanism of action of DPP-4 inhibitors with other oral antidiabetic drugs affords clinicians an effective and well-tolerated treatment option for early and more aggressive management of hyperglycemia in patients with type 2 diabetes.
Freeman
Jeffrey S
JS
Division of Endocrinology and Metabolism, Philadelphia College of Osteopathic Medicine, 4190 City Ave, Suite 234, Philadelphia, PA 19131-1633, USA. jeffreyfreemando@aol.com
D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D018570:Risk Assessment
D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents