Effect of metformin and rosiglitazone on lipid metabolism in HIV infected patients receiving protease inhibitor containing HAART.
OBJECTIVE
Insulin resistance may be the primary event in the protease inhibitor-associated metabolic syndrome. Treatment with insulin sensitizers (metformin, rosiglitazone) can ameliorate insulin resistance. So far, the effects of these agents on blood lipids have not been well determined. The aim of the present study was to evaluate the effects of metformin and rosiglitazone treatment on lipid metabolism in HIV infected patients receiving protease inhibitors containing HAART.


METHODS
HIV infected male patients (>18 years) were eligible for the study if they had impaired glucose tolerance with insulin resistance, characterized by fasting insulin concentration greater then 20 mIU/L and if they were on stable antiretroviral therapy regimen including a protease inhibitor for at least 12 months prior to the study enrolment. The patients were randomly assigned to receive either 1g/day metformin (metformin group, n=30) or 4 mg/day rosiglitazone maleate (rosiglitazone group, n=30) or no treatment (control group, n=30). The primary efficacy parameters were fasting plasma lipids, glucose levels and fasting insulin levels compared between baseline and week 48, by treatment groups.


RESULTS
The total cholesterol concentration in rosiglitazone group increased from 5.76 -/+1.2 to 7.1-/+1.6 mmol/l (23% increase, p<0.05), HDL levels increased from 0.91-/+0.44 to 1.3-/+0.2 (38% increase, p<0.01) and LDL levels increased from 3.5-/+0.98 to 4.5-/+1.0 (28% increase, p<0.05). Treatment with metformin had no significant effect on total, HDL and LDL cholesterol. After 48 weeks of treatment, the fasting triglycerides concentration in the metformin group declined from 4.1-/+1.6 to 3.2-/+1.3 mmol/l (22% decrease,p<0.05) but in the rosiglitazone group no statistically significant effect on plasma triglycerides was noted. Furthermore, after 48 weeks of treatment the fasting insulin concentration in the rosiglitazone group declined by 49% and in the metformin group by 28%. This improvement in insulin secretion could be clearly demonstrated when the sums of insulin concentrations after oral glucose tolerance test were compared: 548-/+13 to 345-/+11.8 mIU/l in the rosiglitazone group (37% decrease, p<0.01) and from 552-/+15 to 420-/+12 mIU/l in the metformin group (24% decrease, p<0.01).


CONCLUSIONS
The study demonstrates that both therapies improve insulin resistance. However, treatment with metformin has no effect on total, HDL and LDL cholesterol, but significantly reduces triglycerides, which has beneficial effect on the lipid status in these patients. Rosiglitazone causes significant increases in total cholesterol, HDL and LDL, but has no effect on triglycerides concentrations.
Tomazic
Janez
J
Dept. of Infectious Diseases and febrile Illnesses, University Medical Centre Ljubljana, Japljeva 2, 1000, Ljubljana, Slovenia.
Karner
Primoz
P
Vidmar
Ludvik
L
Maticic
Mojca
M
Sharma
Prem M
PM
Janez
Andrej
A
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007333:Insulin Resistance / Q000502:physiology; D008055:Lipids / Q000097:blood*; D008297:Male; D008687:Metformin / Q000494:pharmacology*; D008875:Middle Aged; D011446:Prospective Studies; D011480:Protease Inhibitors / Q000627:therapeutic use*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D007004:Hypoglycemic Agents; D008055:Lipids; D011480:Protease Inhibitors; D045162:Thiazolidinediones; D014280:Triglycerides; D000077154:Rosiglitazone; D008687:Metformin