Combination therapy with insulin glargine plus metformin but not insulin glargine plus sulfonylurea provides similar glycemic control to triple oral combination therapy in patients with type 2 diabetes uncontrolled with dual oral agent therapy.
OBJECTIVE
Evaluate substituting insulin glargine (GLAR) for a thiazolidinedione (TZD) versus adding a third oral antidiabetes drug (OAD) in patients with uncontrolled type 2 diabetes mellitus (T2DM) on TZD+metformin or TZD+sulfonylurea.


METHODS
In this multicenter, open-label study, 337 T2DM patients with a glycated hemoglobin A1c (A1C) of 7.5-12.0% despite≥3months of treatment with a TZD plus metformin or a sulfonylurea were randomized to a third OAD (3OAD; metformin or glyburide) or GLAR+1 OAD (metformin or sulfonylurea) with TZD cessation, titrated to a fasting blood glucose≤94mg/dL.


RESULTS
Substitution of GLAR for a TZD led to an adjusted mean A1C change from baseline of-1.66% versus-1.86% in the 3OAD arm (adjusted mean difference 0.20 [95% confidence interval, - 0.11, 0.51], not meeting the noninferiority criteria). This difference was driven by the GLAR+sulfonylurea stratum. GLAR+metformin was as effective as 3OAD in achieving glycemic control but with greater improvements in lipid parameters, less weight gain, and lower hypoglycemia rates.


CONCLUSIONS
These findings favor substitution of GLAR for a TZD in T2DM patients not controlled on TZD+metformin. GLAR+sulfonylurea was less effective at lowering A1C than 3OAD and not associated with the benefits observed with GLAR+metformin.
Baylor University Medical School, Dallas, TX, USA. Electronic address: priscilh@BaylorHealth.edu.
Priscilla
P
Hollander
Cedar-Crosse Research Center, Chicago, IL, USA.
Danny
D
Sugimoto
Sanofi US, Inc., Bridgewater, NJ, USA.
Aleksandra
A
Vlajnic
Washington University School of Medicine, St Louis, MO, USA.
Charles
C
Kilo
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D016903:Drug Monitoring; D004351:Drug Resistance; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005905:Glyburide / Q000009:adverse effects / Q000627:therapeutic use; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control*; D006949:Hyperlipidemias / Q000150:complications / Q000517:prevention & control; D007003:Hypoglycemia / Q000139:chemically induced / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000069036:Insulin Glargine / Q000009:adverse effects / Q000627:therapeutic use*; D057194:Intention to Treat Analysis; D008687:Metformin / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D010352:Patient Dropouts; D013453:Sulfonylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use; D045162:Thiazolidinediones / Q000009:adverse effects / Q000627:therapeutic use; D015430:Weight Gain / Q000187:drug effects
D001786:Blood Glucose; D005905:Glyburide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069036:Insulin Glargine; D008687:Metformin; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones; C517652:hemoglobin A1c protein, human
Glycemic control; Hypoglycemia; Insulin glargine; Oral antidiabetes drug; Type 2 diabetes mellitus