Effect of rosiglitazone and metformin on insulin resistance in patients infected with human immunodeficiency virus receiving highly active antiretroviral therapy containing protease inhibitor: randomized prospective controlled clinical trial.
OBJECTIVE
To evaluate and compare effects of 48-week treatment with rosiglitazone and metformin on insulin resistance in patients infected with Human Immunodeficiency Virus (HIV) receiving highly active antiretroviral therapy (HAART), containing a protease inhibitor.


METHODS
Randomized prospective controlled clinical trial enrolled 90 male patients infected with HIV and having impaired glucose tolerance and insulin resistance (fasting insulin concentration >20 mIU/L). The patients were randomly assigned into three groups; the first group receiving 4 mg rosiglitazone once a day, the second group receiving 500 mg metformin two times a day, and the third group serving as control without hypoglycemic treatment. The primary efficacy parameters were fasting plasma glucose and insulin levels compared between baseline and week. Data on insulin resistance and beta cell function were analyzed by the Homeostasis Model Assessment (HOMA).


RESULTS
After 48 weeks of treatment, the fasting insulin concentration (+/-standard deviation) in rosiglitazone group significantly declined from 39.0+/-3.35 to 19.7+/-3.99 mIU/L (P<0.001; 49% decrease) and in metformin group from 40.3+/-2.29 to 29.2+/-2.82 mIU/L (P<0.001; 27% decrease). HOMA indicated that rosiglitazone significantly reduced insulin resistance from 11.3+/-1.03 to 4.0+/-0.95 (P<0.001), compared with metformin which reduced it from 11.9+/-0.73 to 5.7+/-0.62 (P<0.001). Insulin resistance was significantly lower in the rosiglitazone group after 48 weeks (P<0.001). Metformin significantly improved beta cell function (from 257.3+/-21.91 to 707.4+/-207.32; P<0.001), as did rosiglitazone as well (from 261.3+/-27.98 to 403.3+/-162.50; P<0.001), but the improvement in the metformin group was significantly better (P<0.001). However, metformin was more efficient in improving beta cell function (from 257.3+/-21.91 to 707.4+/-207.32) than rosiglitazone (from 261.3+/-27.98 to 403.3+/-162.50).


CONCLUSIONS
Both rosiglitazone and metformin were effective and well tolerated in HIV treated with protease inhibitor-containing HAART. Rosiglitazone significantly more reduced insulin resistance, while beta cell function was significantly better in patients on metformin. Both drugs may be considered as an appropriate therapy, with rosiglitazone being a better alternative in treating insulin resistance in this patient population. ClinicalTrials.gov trial registration number: NCT00483392.
Silic
Anja
A
Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia.
Janez
Andrej
A
Tomazic
Janez
J
Karner
Primoz
P
Vidmar
Ludvik
L
Sharma
Prem
P
Maticic
Mojca
M
D000293:Adolescent; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D001786:Blood Glucose / Q000378:metabolism; D004334:Drug Administration Schedule; D005215:Fasting; D005500:Follow-Up Studies; D005951:Glucose Tolerance Test; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D011446:Prospective Studies; D011480:Protease Inhibitors / Q000627:therapeutic use*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D011480:Protease Inhibitors; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D008687:Metformin