Metformin Increases HDL3–Cholesterol and Decreases Subcutaneous Truncal Fat in Nondiabetic Patients with HIV-Associated Lipodystrophy

Abstract

The purpose of this study was to assess metformin effects on high-density lipoprotein (HDL) composition of patients with HIV-associated lipodystrophy (LDHIV). Twenty-four adult outpatients were enrolled to receive metformin (1700 mg/d) during 6 months, but 2 were lost to follow-up and 6 stopped the drug due to adverse events (gastrointestinal in 5, and excessive weight loss in 1). From the 16 subjects who completed the study, 69% were female. At baseline, 3 and 6 months, we assessed: weight, waist and hip circumferences, blood pressure, fasting glucose and insulin, homeostasis model assessment of insulin resistance (HOMA2-IR), lipids, and HDL subfractions by microultracentrifugation. At 0 and 6 months, body fat distribution was assessed by computed tomography (CT) scan (L4 and middle femur). Metformin use was associated with reduction of mean weight (-2.4Kg at 6 months; p < 0.001), body mass index, waist, waist-to-hip ratio and a marked decrease in blood pressure (p < 0.001). Subcutaneous (p = 0.01) and total abdominal fat (p = 0.002) were reduced, but no change was found in visceral or thigh fat. No difference was detected on plasma glucose, insulin, HOMA2-IR, cholesterol or triglycerides, except for an increase in HDL3-cholesterol (from 21 mg/dL to 24 mg/dL, p = 0.002) and a reduction of nascent HDL (the fraction of plasma HDL-cholesterol not associated to subfractions HDL2 or HDL3) (p = 0.008). Adverse effects were very common, but most were gastrointestinal and mild. Thus, metformin use in LDHIV increases HDL3-cholesterol (probably due to improved maturation of HDL) and decreases blood pressure, weight, waist, and subcutaneous truncal fat, making this an attractive option for preventing cardiovascular disease in this population.

Searching for biomarkers of comorbidities in sera of treated HIV‐infected patients by isoelectric focusing

“…AMPK activation may be a defense mechanism to counteract chronic inflammation and alteration in lipid metabolism. In agreement, treatment of patients infected with HIV with the antidiabetic drug metformin, an AMPK activator, has been associated with sustained benefits on markers of cardiovascular risk and improvement of lipoatrophy . Chronic comorbidities could explain levels of AMPK, which remained elevated over time during our follow‐up studies.…”

Lipodystrophy: pathophysiology and advances in treatment

“…Metformin is safe and generally well-tolerated; although gastrointestinal symptoms are common, they are mild and usually transient. However, not all subsequent studies have shown consistent improvements in insulin resistance, lipid profile, or anthropometric features 81,82 . Furthermore, metformin may worsen peripheral fat loss, and should therefore be used with caution in lipoatrophic patients 83 .…”

Metformin (dimethyl-biguanide) induced DNA damage in mammalian cells

“…It is prescribed for patients suffering from a variety of insulin-resistant and prediabetic states, including impaired glucose tolerance, obesity (Tankova et al , 2003; Rotella et al , 2006; Hirsch et al , 2009) and metabolic abnormalities associated with HIV disease (Hadigan et al , 2000; Johnson et al , 2005; Diehl et al , 2008). Furthermore, metformin is also used regulating anovulation, and induce and sustain pregnancy in polycystic-ovary syndrome patients (Jakubowicz et al , 2002; De Leo et al , 2006; Lilja and Mathiesen, 2006; Brassard et al , 2008).…”