Insulin resistance is a relatively common finding in chronic HIV infection and its treatment. The cycle of insulin resistance affects not only blood sugars and glucose tolerance but also fat metabolism and fat deposits. Thus, insulin resistance has been the topic of a lot of interest for treatment of the chronic ills associated with changes in glucose and fat metabolism. After discouraging results from previous studies on the insulin-sensitizing drugs rosiglitazone and metformin to improve the fat changes seen in chronic HIV infection, especially with a history of stavudine use, there is some encouraging news on the potential for these therapies to improve insulin sensitivity. While the medications may be used to improve blood sugar control for patients with diabetes, they both have interesting effects on fat metabolism and accumulation.
Both medications can improve insulin sensitivity. However, they have somewhat different effects on lipodystrophy because they target different aspects of fat metabolism. [See the accompanying comparison of effects below.]
Metformin works primarily in the liver to reduce the production of fat, while rosiglitazone works more in the peripheral areas of the body to improve the deposits of fat in subcutaneous areas (the pinchable kind). Because of this, metformin might contribute to the reduction of visceral fat accumulation (bellies and other central fat deposits) and rosiglitazone (and pioglitazone) may potentially improve fat deposits to bring back those lovely body shapes in the legs and arms. We might even see some future studies on the effect of fat maintenance in the face.
On the topic of glitazones, a study of pioglitazone treatment showed improvement in limb fat that was considered significant in participants who were not using stavudine, which seems to have a limiting effect on the potential for glitazone therapy to reverse fat losses. However, on the upside, patients using pioglitazone didn't see any real further losses of fat, which suggests that its prevention potential might be worthy of investigation.
It would be nice to think that all is beneficial, but we know better at this point than to expect only good things with as much experience as we have all had with multiple medications over long periods of time. Metformin may lower the 'bad' LDL cholesterol and raise the 'good' HDL cholesterol somewhat, while rosiglitazone may increase LDL. Metformin use has its downsides, such as the small potential for lactic acidosis. Patients taking metformin did not see benefit in gaining limb fat and may have even experienced continued losses. Varying results in the ability of metformin to reduce visceral fat volume suggests that its best use will be in cases of significant insulin resistance with a good amount of limb fat at baseline. The glitazones can be used without significant insulin resistance but should be watched for their contributions to changing blood-fat levels that may contribute to risk for heart disease.
There are some limitations, and as you can imagine, there's need for more study in this area. Studies on these medications have involved relatively small numbers and were short in duration. It may take some time for each of these medications to show results that you can see in the mirror.
Meanwhile, as you look over the options presented by this latest round of hopeful research with your health care team, it is a good time to renew your vow to take a look at your diet and exercise options to control the effects of insulin resistance. The benefits could be even better than expected if you start your own campaign to improve insulin resistance by combining any medication efforts with diet and exercise.
Drug Effects on the BodyMetformin
Weight: Lowers it
Body mass index: Lowers it
Waist circumference: Lowers it
Subcutaneous fat mass: Lowers it
Visceral fat mass: Lowers it
LDL cholesterol: Lowers it
HDL cholesterol: Increases it
Weight: Increases it
Body mass index: Increases it
Waist circumference: No significant change
Subcutaneous fat mass: Increases it
Visceral fat mass: No significant change
LDL cholesterol: Increases it
HDL cholesterol: Increases it
Fields-Gardner is the director of services for the HIV nutrition company Cutting Edge and is a member of the International AIDS Society and the American Dietetic Association's Dietetic Practice Group on HIV and AIDS. E-mail her at email@example.com.