c-peptide and Headache

Sitagliptin (MK-0431 [(2R)-4-oxo-4-(3-[trifluoromethyl]-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7[8H]-yl)-1-(2,4,5-trifluorophenyl)butan-2-amine]) is an orally active, potent, and selective inhibitor of dipeptidyl peptidase IV (DPP-IV) currently in phase III development for the treatment of type 2 diabetes.. Two double-blind, randomized, placebo-controlled, alternating-panel studies evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of single oral doses of sitagliptin (1.5-600 mg) in healthy male volunteers.. Sitagliptin was well absorbed (approximately 80% excreted unchanged in the urine) with an apparent terminal half-life ranging from 8 to 14 hours. Renal clearance of sitagliptin averaged 388 mL/min and was largely uninfluenced by the dose administered. The area under the plasma concentration-time curve for sitagliptin increased in an approximately dose-dependent manner and was not meaningfully influenced by food. Single doses of sitagliptin markedly and dose-dependently inhibited plasma DPP-IV activity, with approximately 80% or greater inhibition of DPP-IV activity occurring at 50 mg or greater over a 12-hour period and at 100 mg or greater over a 24-hour period. Compared with placebo, sitagliptin produced an approximately 2-fold increase in postmeal active glucagon-like peptide 1 levels. Sitagliptin was well tolerated and was not associated with hypoglycemia.. This study provides proof of pharmacologic characteristics for sitagliptin in humans. By inhibiting plasma DPP-IV activity, sitagliptin increases the postprandial rise in active glucagon-like peptide 1 concentrations without causing hypoglycemia in normoglycemic healthy male volunteers. Sitagliptin possesses pharmacokinetic and pharmacodynamic characteristics that support a once-daily dosing regimen.

Topics: Administration, Oral; Adolescent; Adult; Analysis of Variance; Area Under Curve; Blood Glucose; C-Peptide; Common Cold; Dipeptidyl Peptidase 4; Dose-Response Relationship, Drug; Double-Blind Method; Enzyme Inhibitors; Eye Diseases; Fasting; Glucagon-Like Peptide 1; Half-Life; Headache; Humans; Insulin; Male; Middle Aged; Pyrazines; Sitagliptin Phosphate; Triazoles

In patients with diabetes mellitus (DM), there are changes in vascular reactivity and nerve conduction that may be relevant for migraine pathophysiology. However, previous studies on the relationship between headache and DM have shown conflicting results. The aim of the present study was to investigate a possible association between headache and DM in a large population-based cross-sectional study. Associations were assessed in multivariate analyses, estimating prevalence odds ratios (ORs) with 95% confidence intervals (CIs). Prevalence OR of migraine was lower amongst persons with DM compared with those without DM, the OR being 0.4 (95% CI: 0.2-0.9) for type 1 and 0.7 (95% CI: 0.5-0.9) for type 2 DM. Furthermore, OR of headache were lower amongst those with duration of DM > or = 13 years compared with those who had got DM the last 3 years, OR 0.6 (95% CI: 0.4-0.9). The analyses revealed no clear associations between non-migrainous headache and DM. The reason for the inverse relationship between migraine and DM is unknown, but might be related to pathophysiological abnormalities in patients with DM that protect against migraine.

Topics: Adult; Aged; Aged, 80 and over; Autoantibodies; Blood Glucose; C-Peptide; Cross-Sectional Studies; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glutamate Decarboxylase; Glycated Hemoglobin; Headache; Humans; Male; Middle Aged; Migraine Disorders; Norway; Odds Ratio; Surveys and Questionnaires