nateglinide and pasireotide

Pasireotide, a multireceptor-targeted somatostatin analogue with efficacy in Cushing's disease and acromegaly, can affect glucose metabolism due to inhibition of insulin secretion and incretin hormone responses. A study was therefore conducted to evaluate different antihyperglycemic drugs in the management of pasireotide-associated hyperglycemia.. This was a 1-week, Phase I, open-label study. Healthy male volunteers were randomized to pasireotide 600 μg sc bid alone or co-administered with metformin 500 mg po bid, nateglinide 60 mg po tid, vildagliptin 50mg po bid, or liraglutide 0.6 mg sc qd. An oral glucose tolerance test (OGTT) was performed on days 1 and 7 to evaluate effects on serum insulin, plasma glucose and glucagon levels. Safety/tolerability and pharmacokinetic effects were also evaluated.. Ninety healthy male volunteers were enrolled (n=18 per arm). After 7 days of treatment, plasma glucose AUC post-OGTT increased by 69% with pasireotide alone. The effect was reduced by 13%, 29%, 45% and 72% with co-administration of metformin, nateglinide, vildagliptin and liraglutide, respectively. On day 7, compared with pasireotide alone, the decrease in serum insulin was attenuated with nateglinide, metformin, liraglutide and vildagliptin co-administration (levels were 3%, 6%, 34% and 71% higher, respectively). Minimal changes in plasma glucagon were observed. Adverse events were consistent with the safety profiles of the drugs used.. Vildagliptin and liraglutide were most effective in minimizing pasireotide-associated hyperglycemia in healthy volunteers.

Topics: Adamantane; Adolescent; Adult; Blood Glucose; Cyclohexanes; Dipeptidyl-Peptidase IV Inhibitors; Drug Therapy, Combination; Glucagon; Glucagon-Like Peptide 1; Glucose Tolerance Test; Healthy Volunteers; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Liraglutide; Male; Maximum Tolerated Dose; Metformin; Middle Aged; Nateglinide; Nitriles; Phenylalanine; Prognosis; Pyrrolidines; Somatostatin; Vildagliptin; Young Adult