Synthetic exendin-4 (exenatide) significantly reduces postprandial and fasting plasma glucose in subjects with type 2 diabetes.
Despite the advent of new treatments, glucose control in the type 2 diabetes population is unsatisfactory. AC2993 (synthetic exendin-4; exenatide), a novel glucose-dependent insulinotropic agent, exhibited notable antidiabetic potential in two clinical studies in patients with type 2 diabetes. In study A, 24 subjects received sc injections of study medication (0.1 micro g/kg AC2993 or placebo) twice daily with meals for 5 d. Statistically significant reductions in mean postprandial circulating concentrations of glucose, insulin, and glucagon occurred following treatment with AC2993. In study B, 13 subjects receiving a single dose of study medication (0.05, 0.1, or 0.2 micro g/kg AC2993 or placebo) following an overnight fast had reduced fasting plasma glucose concentrations during the subsequent 8-h period. The relative glucose and insulin concentration profiles were consistent with glucose-dependent insulinotropism. AC2993 was well tolerated. Mild transient headache, nausea, and vomiting were the main adverse events. In conclusion, AC2993 acutely and markedly reduces fasting and postprandial glucose concentrations in patients with type 2 diabetes. During fasting, glucose-dependent enhancement of insulin secretion and suppression of glucagon secretion are the predominant mechanisms, and postprandially, slowing of gastric emptying is additionally operative. This robust antidiabetic effect warrants further evaluation of AC2993.
Kolterman
Orville G
OG
Amylin Pharmaceuticals, Inc., San Diego, California 92121, USA.
Buse
John B
JB
Fineman
Mark S
MS
Gaines
Eling
E
Heintz
Sonja
S
Bicsak
Thomas A
TA
Taylor
Kristin
K
Kim
Dennis
D
Aisporna
Maria
M
Wang
Yan
Y
Baron
Alain D
AD
D000082:Acetaminophen / Q000097:blood / Q000493:pharmacokinetics; D018712:Analgesics, Non-Narcotic / Q000097:blood / Q000493:pharmacokinetics; D001786:Blood Glucose / Q000187:drug effects*; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000178:diet therapy / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D000077270:Exenatide; D005215:Fasting; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects; D005934:Glucagon / Q000097:blood; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000097:blood; D007328:Insulin / Q000008:administration & dosage / Q000097:blood; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage* / Q000009:adverse effects; D019518:Postprandial Period; D014280:Triglycerides / Q000097:blood; D014688:Venoms
D018712:Analgesics, Non-Narcotic; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D010455:Peptides; D014280:Triglycerides; D014688:Venoms; D000082:Acetaminophen; D005934:Glucagon; D000077270:Exenatide