Effects of colesevelam, rosiglitazone, or sitagliptin on glycemic control and lipid profile in patients with type 2 diabetes mellitus inadequately controlled by metformin monotherapy.
OBJECTIVE
To evaluate the glycemic effect of colesevelam, rosiglitazone, or sitagliptin when added to metformin monotherapy in patients with type 2 diabetes mellitus (DM) and to examine the effects of these antidiabetes agents on lipid and lipoprotein levels.


METHODS
This 16-week, open-label pilot study conducted between May 2007 and April 2008 at 20 sites in the United States, 7 sites in Mexico, and 6 sites in Colombia, enrolled adults with inadequately controlled type 2 DM (glycated hemoglobin [HbA1c], 7.0%-10.0%) on a stable metformin regimen (1500-2550 mg daily for > or = 3 months). At Week 0, participants were randomly assigned 1:1:1 to open-label colesevelam hydrochloride, 3.75 g daily; open-label rosiglitazone maleate, 4 mg daily; or open-label sitagliptin phosphate, 100 mg daily, in addition to existing metformin therapy. The primary efficacy variable was the change in HbA1c from baseline to Week 16 with last (post-baseline) observation carried forward.


RESULTS
In total, 169 participants were randomly assigned to treatment groups (colesevelam, n = 57; rosiglitazone, n = 56; and sitagliptin, n = 56), and 141 participants (83.4%) completed the study. Least-squares mean reductions in HbA1c from baseline were observed in all groups at Week 16 last observation carried forward (colesevelam, -0.3% [P<.031]; rosiglitazone: -0.6% [P<.001]; sitagliptin: -0.4% [P<.009]) At study end, 10 of 56 participants (17.9%) in the colesevelam group, 19 of 54 (35.2%) in the rosiglitazone group, and 15 of 55 (27.3%) in the sitagliptin group achieved HbA1c <7.0%. Colesevelam significantly reduced mean low-density lipoprotein (LDL)-cholesterol levels relative to baseline (11.6%), whereas levels were significantly increased with rosiglitazone and sitagliptin at Week 16 last observation carried forward (7.8% and 7.7%, respectively). Twenty-two of 52 participants (42.3%) in the colesevelam group, 12 of 51 (23.5%) in the rosiglitazone group, and 13 of 53 (24.5%) in the sitagliptin group achieved LDL cholesterol <100 mg/dL at Week 16 last observation carried forward.


CONCLUSIONS
All 3 antidiabetes agents significantly improved glycemic control, but only colesevelam also significantly reduced LDL-cholesterol levels in patients with type 2 DM.
Rigby
Scott P
SP
Summit Research Group, Stow, Ohio 44224, USA. srigby@neo.rr.com
Handelsman
Yehuda
Y
Lai
Yu-Ling
YL
Abby
Stacey L
SL
Tao
Ben
B
Jones
Michael R
MR
D000328:Adult; D000499:Allylamine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000069472:Colesevelam Hydrochloride; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D011719:Pyrazines / Q000627:therapeutic use*; D000077154:Rosiglitazone; D000068900:Sitagliptin Phosphate; D045162:Thiazolidinediones / Q000627:therapeutic use*; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use*
D007004:Hypoglycemic Agents; D008055:Lipids; D011719:Pyrazines; D045162:Thiazolidinediones; D014230:Triazoles; D000077154:Rosiglitazone; D000499:Allylamine; D008687:Metformin; D000069472:Colesevelam Hydrochloride; D000068900:Sitagliptin Phosphate