Effect of pioglitazone versus insulin glargine on cardiac size, function, and measures of fluid retention in patients with type 2 diabetes.
BACKGROUND
Both insulin and thiazolidinediones (TZDs) are effective in the treatment of hyperglycaemia and amelioration of insulin resistance in type 2 diabetes but have side effects including weight gain and fluid retention. The use of TZDs has been further hampered by the risk of adverse cardiovascular events including heart failure. The present study evaluated the effect of pioglitazone or insulin glargine on cardiac function and size as well as on surrogate markers of fluid retention such as weight, haemoglobin and natriuretic peptides.


METHODS
Thirty patients with inadequate glycaemic control on metformin and sulfonylurea were randomised to receive add-on therapy with insulin glargine or pioglitazone for 26 weeks. Echocardiographic data and blood samples were collected from the two groups before the start of the treatment and after 26 weeks. Left ventricular end-diastolic and left atrial end-systolic volumes were quantified, weight measured and blood samples analyzed.


RESULTS
After 26 weeks of treatment, the changes in HbA1c, weight and haemoglobin were similar between the two groups. HDL increased significantly in the pioglitazone group. While there was an increase in natriuretic peptides in the pioglitazone group (NT-proBNP 11.4 +/- 19.6 to 22.8 +/- 44.0, p = 0.046), the difference between the treatment groups was not significant. Left ventricular end-diastolic volume increased by 11% and left atrial end-systolic volume by 17% in the pioglitazone group (Both, p < 0.05, between treatment groups). There was a borderline significant increase in ejection fraction in the pioglitazone group.


CONCLUSIONS
This randomised pilot-study showed that six-month treatment with pioglitazone induced significant increases in natriuretic peptides and alterations of cardiac size. These changes were not observed with insulin glargine, which also is known to induce fluid retention. Larger randomised trials are warranted to confirm these findings.
Dorkhan
Mozhgan
M
Department of Clinical Sciences, Division of Diabetes & Endocrinology, Lund University, Malmö University Hospital, Malmö, Sweden. mozhgan.dorkhan@med.lu.se
Dencker
Magnus
M
Stagmo
Martin
M
Groop
Leif
L
D000368:Aged; D016279:Atrial Function, Left / Q000187:drug effects / Q000502:physiology*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004487:Edema / Q000139:chemically induced / Q000473:pathology; D004562:Electrocardiography / Q000379:methods; D005260:Female; D006801:Humans; D007328:Insulin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology; D009929:Organ Size; D010865:Pilot Projects; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology*
D007328:Insulin; D049528:Insulin, Long-Acting; D045162:Thiazolidinediones; D000069036:Insulin Glargine; D000077205:Pioglitazone