Effect on glycemic control of exenatide (synthetic exendin-4) additive to existing metformin and/or sulfonylurea treatment in patients with type 2 diabetes.
OBJECTIVE
AC2993 (synthetic exendin-4; exenatide) is a peptide that enhances glucose-dependent insulin secretion, suppresses inappropriately elevated glucagon secretion, and slows gastric emptying. AC2993 also promotes beta-cell proliferation and neogenesis in vitro and in animal models. This study examines the activity and safety of subcutaneously injected AC2993 in patients with type 2 diabetes currently treated with diet and/or oral antidiabetic agents (OAAs).


METHODS
A total of 109 patients treated with diet and a sulfonylurea and/or metformin were enrolled in a blinded study. Patients were randomly assigned to one of three subcutaneously (SC) injected regimens of AC2993 (0.08 micro g/kg) or placebo for 28 days.


RESULTS
All three AC2993 regimens led to significant reductions in serum fructosamine relative to placebo (P <or= 0.004). Mean reductions ranged from 39 to 46 micro mol/l. All AC2993 groups had reductions in HbA(1c) ranging from 0.7 to 1.1% (P <or= 0.006). An end-of-study HbA(1c) <7% was achieved by 15% of AC2993 patients versus 4% of placebo patients, confirming AC2993 effects on fasting and postprandial glycemia. On days 14 and 28, the beta-cell index (homeostasis model assessment) for patients treated with AC2993 was 50-100% higher than baseline, contrasting with unchanged levels for placebo. The most common adverse event was transient mild-to-moderate nausea.


CONCLUSIONS
AC2993 is a promising therapeutic for patients with type 2 diabetes. In this study, it had significant effects on HbA(1c) levels in patients not currently achieving optimal glucose control with diet and/or OAAs.
Fineman
Mark S
MS
Amylin Pharmaceuticals, Inc., San Diego, California 92121, USA.
Bicsak
Thomas A
TA
Shen
Larry Z
LZ
Taylor
Kristin
K
Gaines
Eling
E
Varns
Amanda
A
Kim
Dennis
D
Baron
Alain D
AD
D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure; D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D000077270:Exenatide; D005260:Female; D019270:Fructosamine / Q000097:blood; D006442:Glycated Hemoglobin / Q000032:analysis; D006339:Heart Rate; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007515:Islets of Langerhans / Q000187:drug effects / Q000502:physiology; D008055:Lipids / Q000097:blood; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D013453:Sulfonylurea Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D014688:Venoms
D001786:Blood Glucose; D000077270:Exenatide; D019270:Fructosamine; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008055:Lipids; D008687:Metformin; D010455:Peptides; D013453:Sulfonylurea Compounds; D014688:Venoms