Glycaemic and nonglycaemic effects of pioglitazone in triple oral therapy of patients with type 2 diabetes.
OBJECTIVE
To examine pioglitazone as add-on to metformin and insulin secretagogues in patients with type 2 diabetes and inadequate glycaemic control and its effect on glycaemic control, surrogate measures of insulin sensitivity (adiponectin) and beta-cell function (proinsulin/insulin) and fluid retention.


METHODS
Prospective open-label study of 54 patients with type 2 diabetes and HbA1c>or=6.5% admitted to outpatient unit at Malmö University Hospital. The patients received 30-45 mg pioglitazone daily during 26 weeks in addition to their existing antidiabetic medication. After 26 weeks, one-third of patients were followed for 3 months without pioglitazone.


RESULTS
HbA1c decreased (7.8+/-0.9-6.3+/-0.9%, P<0.001) with 61% of patients achieving levels<6.5%. However, in the group followed for another 3 months HbA1c increased (6.1+/-0.73-7.1+/-0.9, n=18, P<0.001) after pioglitazone withdrawal. Adiponectin increased (6.1+/-2.8-13.2+/-5.8 microg mL-1, P<0.001) and the proinsulin to insulin ratio decreased (0.89+/-0.66-0.66+/-0.53, P<0.001). Nt-proBNP increased from 487.3+/-252.2 to 657.8+/-392.1 pmol L-1 (P<0.001).


CONCLUSIONS
Pioglitazone is effective in achieving glycaemic targets and reducing risk factors involved in atherosclerosis and improving beta-cell function when used as part of triple oral therapy in patients with type 2 diabetes and secondary drug failure. Nt-proBNP increase with concomitant decrease in haemoglobin suggests a subclinical sign of fluid retention.
Dorkhan
M
M
Division of Diabetes & Endocrinology, Department of Clinical Sciences, Malmö University Hospital, Lund University, Malmö, Sweden. mozhgan.dorkhan@med.lu.se
Magnusson
M
M
Frid
A
A
Grubb
A
A
Groop
L
L
Jovinge
S
S
D052242:Adiponectin / Q000097:blood; D000284:Administration, Oral; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D016022:Case-Control Studies; D055316:Cystatin C; D015891:Cystatins / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D005905:Glyburide / Q000008:administration & dosage; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000097:blood; D008297:Male; D008687:Metformin / Q000008:administration & dosage; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D000077205:Pioglitazone; D011384:Proinsulin / Q000097:blood; D011446:Prospective Studies; D018709:Statistics, Nonparametric; D045162:Thiazolidinediones / Q000008:administration & dosage* / Q000627:therapeutic use
D052242:Adiponectin; D015415:Biomarkers; D001786:Blood Glucose; D055316:Cystatin C; D015891:Cystatins; D005905:Glyburide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin; D020097:Natriuretic Peptide, Brain; D010446:Peptide Fragments; D000077205:Pioglitazone; D011384:Proinsulin; D045162:Thiazolidinediones; C525030:CST3 protein, human; C109794:pro-brain natriuretic peptide (1-76)