Management of hyperglycemia associated with pasireotide (SOM230): Healthy volunteer study

Abstract

AimsPasireotide, 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. MethodsThis was a 1-week, Phase I, open-label study. Healthy male volunteers were randomized to pasireotide 600μg sc bid alone or co-administered with metformin 500mg po bid, nateglinide 60mg po tid, vildagliptin 50mg po bid, or liraglutide 0.6mg 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. ResultsNinety 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. ConclusionsVildagliptin and liraglutide were most effective in minimizing pasireotide-associated hyperglycemia in healthy volunteers.