A programme of cardiovascular and resistance exercise and use of the anti-diabetes drug metformin resulted in significantly greater reductions in risk factors for cardiovascular disease in HAART-treated HIV-positive patients than treatment with metformin alone, according to a US study published in the February 20th edition of AIDS. The investigators, from the Massachusetts General Hospital and the Harvard Medical School, also established that patients undertaking exercise at the same time as taking metaformin experienced an improvement in their body strength and reduction in their waist-to-hip ratio.
Metformin has been shown to reduce cardiovascular risk factors and improve insulin sensitivity in HIV-positive patients who developed insulin resistance and experienced fat accumulation around the trunk after the initiation of highly active antiretroviral therapy (HAART). Disturbances in glucose levels, insulin resistance and fat redistribution have been reported in people treated with a wide range of HAART regimens.
An exercise regimen consisting of both cardiovascular and resistance training has been shown to moderate many of the potential risk factors for cardiovascular disease in HAART-treated patients with lipodystrophy, including the lowering of blood pressure, a reduction in weight, a reduction in blood lipids and an improvement in waist-to-hip ratio (waist-to-hip ratio indicates the severity of central fat accumulation, which appears to increase the risk of cardiovascular disease).
The Massachusetts investigators conducted a prospective randomised study between 2000 and 2002 to see if patients with body fat redistribution and insulin resistance experienced a more effective reduction in their cardiovascular disease risk factors than individuals treated with metformin alone.
A total of 37 individuals were recruited to the study. They were aged between 18 and 60 years, and all were on a stable HAART regimen. To be included in the study, it was necessary for individuals to have a fasting insulin level of above 104pmol/l and evidence of fat redistribution.
After an overnight fast, the study participants had their insulin, triglycerides and cholesterol tested and tests were also conducted to determine HIV viral load and resting lactate levels. Waist-to-hip ratio, height, and weight were also measured, and a DEXA scan was used to assess body fat redistribution. Cardiovascular fitness was also tested.
Patients were then randomised to receive treatment with metformin at a dose of 500mg twice daily, with dose escalation to 850mg twice daily after two weeks, or the same metformin regimen in combination with an exercise programme consisting of an hour of cardiovascular and weight training three times a week for twelve weeks.
The two groups of patients had comparable insulin profiles and cardiovascular disease risk factors at baseline.
A total of twelve patients (eight in the exercise group and four in the metformin only arm) withdrew from the study. One patient in each arm withdrew after increases in their resting lactic acid levels, and one patient from each group withdrew after abnormal liver function results.
Patients in the exercise arm experienced a greater fall in their median systolic (p=0.012) and diastolic (p=0.001) blood pressure than individuals in the metformin only arm. In addition, the waist-to-hip ratio improved to a greater extent in the exercise/metformin arm than in the metformin-only arm, as did the fasting insulin (p
However, improvements in lipids and resting lactate were comparable between the two groups of patients.
The investigators conclude that: “our study…suggests that a thrice-weekly aerobic and resistance training programme in combination with metformin significantly improves cardiovascular parameters and aerobic endurance in hyperinsulinemic, lipodystrophic HIV patients.”
They caution, however, that metformin, combined with exercise, is not recommended for patients with lipoatrophy and insulin resistance, due to the potential for further weight loss.
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Driscoll SD et al. Effects of exercise training and metformin on body composition and cardiovascular indices in HIV-infected patients. AIDS 18: 465 – 473, 2004.