Further improvement in postprandial glucose control with addition of exenatide or sitagliptin to combination therapy with insulin glargine and metformin: a proof-of-concept study.
OBJECTIVE
To assess the effect of a 4-week adjunctive therapy of exenatide (EXE) (5-10 microg b.i.d.) or sitagliptin (SITA) (100 mg once daily) in response to a standardized breakfast meal challenge in 48 men or women with type 2 diabetes receiving insulin glargine (GLAR) + metformin (MET).


METHODS
This was a single-center, randomized, open-label, active comparator-controlled study with a three-arm parallel group design, consisting of: screening, 4- to 8-week run-in period, 4-week treatment period, and follow-up. In all three groups, the GLAR dose was titrated according to an algorithm (fasting blood glucose <or=100 mg/dl).


RESULTS
The unadjusted 6-h postprandial blood glucose excursion of both GLAR + MET + EXE and GLAR + MET + SITA was statistically significantly smaller than that of GLAR + MET (606 +/- 104 vs. 612 +/- 133 vs. 728 +/- 132 mg/dl/h; P = 0.0036 and 0.0008). A1C significantly decreased in all three groups (P < 0.0001), with the greatest reduction of -1.9 +/- 0.7 under GLAR + MET + EXE (GLAR + MET + SITA -1.5 +/- 0.7; GLAR + MET -1.2 +/- 0.5%-points; GLAR + MET + EXE vs. GLAR + MET P = 0.0154). The American Diabetes Association A1C target of <7.0% was reached by 80.0, 87.5, and 62.5% of subjects, respectively. GLAR + MET + EXE had the highest number (47) of adverse events, mostly gastrointestinal (56%) with one dropout. GLAR + MET or GLAR + MET + SITA only had 10 and 12 adverse events, respectively, and no dropouts. Hypoglycemia (blood glucose <50 mg/dl) rates were low and comparable among groups. Weight decreased with GLAR + MET + EXE (-0.9 +/- 1.7 kg; P = 0.0396) and increased slightly with GLAR + MET (0.4 +/- 1.5 kg; NS; GLAR + MET + EXE vs. GLAR + MET P = 0.0377).


CONCLUSIONS
EXE or SITA added to GLAR + MET further substantially reduced postprandial blood glucose excursions. Longer-term studies in a larger population are warranted to confirm these findings.
Arnolds
Sabine
S
Profil Institut für Stoffwechselforschung, Neuss, Germany. sabine.arnolds@profil-research.de
Dellweg
Sibylle
S
Clair
Janina
J
Dain
Marie-Paule
MP
Nauck
Michael A
MA
Rave
Klaus
K
Kapitza
Christoph
C
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D000077270:Exenatide; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007328:Insulin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D014688:Venoms / Q000008:administration & dosage* / Q000009:adverse effects
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D049528:Insulin, Long-Acting; D010455:Peptides; D014688:Venoms; D000069036:Insulin Glargine; D008687:Metformin; D000077270:Exenatide