Exenatide versus glibenclamide in patients with diabetes.
BACKGROUND
Incretin-based therapies have provided additional options for the treatment of type 2 diabetes mellitus. The aim of our study was to evaluate the effects of exenatide compared to glibenclamide on body weight, glycemic control, beta-cell function, insulin resistance, and inflammatory state in patients with diabetes.


METHODS
One hundred twenty-eight patients with uncontrolled type 2 diabetes mellitus receiving therapy with metformin were randomized to take exenatide 5 microg twice a day or glibenclamide 2.5 mg three times a day and titrated to exenatide 10 microg twice a day or glibenclamide 5 mg three times a day. We evaluated body weight, body mass index (BMI), glycated hemoglobin (HbA(1c)), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance (HOMA-IR) index, homeostasis model assessment beta-cell function (HOMA-beta) index, plasma proinsulin (PPr), PPr/FPI ratio, resistin, retinol binding protein-4 (RBP-4), and high-sensitivity C-reactive protein (Hs-CRP) at baseline and after 3, 6, 9, and 12 months.


RESULTS
Body weight and BMI decreased with exenatide and increased with glibenclamide. A similar improvement of HbA(1c), FPG, and PPG was obtained in both groups, whereas FPI decreased with exenatide and increased with glibenclamide. The HOMA-IR index decreased and the HOMA-beta index increased with exenatide but not with glibenclamide. A decrease of PPr was reported in both groups, but only glibenclamide decreased the PPr/FPI ratio. Resistin and RBP-4 decreased with exenatide and increased with glibenclamide. A decrease of Hs-CRP was obtained with exenatide, whereas no variations were observed with glibenclamide.


CONCLUSIONS
Both exenatide and glibenclamide gave a similar improvement of glycemic control, but only exenatide gave improvements of insulin resistance and beta-cell function, giving also a decrease of body weight and of inflammatory state.
Department of Internal Medicine and Therapeutics, University of Pavia, Italy. giuseppe.derosa@unipv.it
G
G
Derosa
P
P
Maffioli
S A T
SA
Salvadeo
I
I
Ferrari
P D
PD
Ragonesi
F
F
Querci
I G
IG
Franzetti
G
G
Gadaleta
L
L
Ciccarelli
M N
MN
Piccinni
A
A
D'Angelo
A F G
AF
Cicero
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000187:drug effects; D015992:Body Mass Index; D001835:Body Weight / Q000187:drug effects; D002097:C-Reactive Protein / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D000077270:Exenatide; D005260:Female; D005905:Glyburide / Q000627:therapeutic use*; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D054795:Incretins / Q000819:agonists; D007333:Insulin Resistance / Q000502:physiology; D050417:Insulin-Secreting Cells / Q000187:drug effects; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D010455:Peptides / Q000627:therapeutic use*; D011384:Proinsulin / Q000097:blood; D052243:Resistin / Q000097:blood; D054839:Retinol-Binding Proteins, Plasma / Q000032:analysis; D014688:Venoms / Q000627:therapeutic use*; D055815:Young Adult
D001786:Blood Glucose; D002097:C-Reactive Protein; D000077270:Exenatide; D005905:Glyburide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D054795:Incretins; D008687:Metformin; D010455:Peptides; D011384:Proinsulin; D052243:Resistin; D054839:Retinol-Binding Proteins, Plasma; D014688:Venoms; C101326:RBP4 protein, human