Exenatide suppresses postprandial elevations in lipids and lipoproteins in individuals with impaired glucose tolerance and recent onset type 2 diabetes mellitus.
OBJECTIVE
Chronic exenatide treatment in type 2 diabetes is associated with improved glucose control and fasting lipid levels, as well as weight loss. Less established is whether exenatide directly reduces postprandial lipid and lipoprotein levels without the reduction in body weight or fasting glucose and triglycerides levels that frequently occur with prolonged therapy. Therefore, the effect of a single injection of exenatide on postprandial lipids, remnant lipoproteins, and apolipoproteins was studied.


METHODS
A double-blinded, randomized, placebo-controlled, crossover study was conducted in 35 subjects (31 men and 4 women) with impaired glucose tolerance (n=20) or recent onset type 2 diabetes (n=15). A single subcutaneous injection of exenatide (10 microg) or normal saline was administered just prior to a high-calorie, fat-enriched breakfast meal. Concentrations of triglycerides (TG), apolipoproteins B-48 and CIII, non-esterified fatty acids (NEFA), and remnant lipoprotein (RLP) cholesterol and TG in serum or plasma were measured prior to the injection and for up to 8 h postprandially.


RESULTS
Exenatide markedly reduced postprandial elevation of TG, apolipoproteins B-48 and CIII, RLP-cholesterol and RLP-triglyceride (all p<0.001). Postprandial declines in NEFA were less pronounced but persisted longer with exenatide compared to placebo (p<0.05). These effects of exenatide were not affected either by glucose tolerance status or by treatment with statins.


CONCLUSIONS
These results demonstrate that exenatide acutely and profoundly inhibits postprandial excursions of proatherogenic lipids and lipoproteins and may offer additional cardiovascular risk reduction (NCT00974272).
Schwartz
Eric A
EA
Department of Endocrinology, Phoenix VA Health Care System, 650 E. Indian School Road (111E), Phoenix, AZ 85012-1892, USA. eric.schwartz@va.gov
Koska
Juraj
J
Mullin
Michael P
MP
Syoufi
Iyad
I
Schwenke
Dawn C
DC
Reaven
Peter D
PD
D000328:Adult; D000368:Aged; D053283:Apolipoprotein B-48 / Q000097:blood; D053305:Apolipoprotein C-III / Q000097:blood; D001130:Arizona; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004041:Dietary Fats / Q000008:administration & dosage / Q000378:metabolism; D004311:Double-Blind Method; D002149:Energy Intake; D000077270:Exenatide; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D018149:Glucose Intolerance / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000097:blood*; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage / Q000627:therapeutic use*; D019518:Postprandial Period; D013997:Time Factors; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood; D014688:Venoms / Q000008:administration & dosage / Q000627:therapeutic use*
D053283:Apolipoprotein B-48; D053305:Apolipoprotein C-III; D015415:Biomarkers; D001786:Blood Glucose; D004041:Dietary Fats; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D007328:Insulin; D008055:Lipids; D008074:Lipoproteins; D010455:Peptides; D014280:Triglycerides; D014688:Venoms; C112017:remnant-like particle cholesterol; D002784:Cholesterol; D000077270:Exenatide