The efficacy and safety of insulin-sensitizing drugs in HIV-associated lipodystrophy syndrome: a meta-analysis of randomized trials
Open accessAbstract
BACKGROUND: HIV-associated lipodystrophy syndrome (HALS) is characterized by insulin resistance, abnormal lipid metabolism and redistribution of body fat. To date, there has been no quantitative summary of the effects of insulin sensitizing-agents for the treatment of this challenging problem. METHODS: We searched MEDLINE, the Cochrane Library, clinical trial registries, conference proceedings and references for randomized trials evaluating rosiglitazone, pioglitazone or metformin in patients with evidence of HALS (last update December 2009). Two reviewers independently abstracted data and assessed quality using a standard form. We contacted authors for missing data and calculated weighted mean differences (WMD) and 95% confidence intervals (CI) for each outcome. RESULTS: Sixteen trials involving 920 patients met inclusion criteria. Rosiglitazone modestly improved fasting insulin (WMD -3.67 mU/L; CI -7.03, -0.31) but worsened triglycerides (WMD 32.5 mg/dL; CI 1.93, 63.1), LDL (WMD 11.33 mg/dL; CI 1.85, 20.82) and HDL (WMD -2.91 mg/dL; CI -4.56, -1.26) when compared to placebo or no treatment in seven trials. Conversely, pioglitazone had no impact on fasting insulin, triglycerides or LDL but improved HDL (WMD 7.60 mg/dL; CI 0.20, 15.0) when compared to placebo in two trials. Neither drug favorably impacted measures of fat redistribution. Based on six trials with placebo or no treatment controls, metformin reduced fasting insulin (WMD -8.94 mU/L; CI -13.0, -4.90), triglycerides (WMD -42.87 mg/dL; CI -73.3, -12.5), body mass index (WMD -0.70 kg/m2; CI -1.09, -0.31) and waist-to-hip ratio (WMD -0.02; CI -0.03, 0.00). Three trials directly compared metformin to rosiglitazone. While effects on insulin were comparable, lipid levels and measures of fat redistribution all favored metformin. Severe adverse events were uncommon in all 16 trials. CONCLUSION: Based on our meta-analysis, rosiglitazone should not be used in HALS. While pioglitazone may be safer, any benefits appear small. Metformin was the only insulin-sensitizer to demonstrate beneficial effects on all three components of HALS.
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Metformin reduces visceral abdominal fat in patients with HIV lipodystrophy.
“Metformin has been shown to reduce VAT [97,98]”
From Metformin: An Old But Still the Best Treatment for Type 2 Diabetes (2013) · cites this paper as [98]
Metformin has favorable effects on insulin levels, insulin sensitivity, weight, flow-mediated vasodilation, and lipid profiles in HIV lipodystrophy.
“Favorable effects on insulin levels [98], insulin sensitivity [119], weight [97], flow-mediated vasodilation [119], and lipid profiles [98,119] have also been described.”
From Metformin: An Old But Still the Best Treatment for Type 2 Diabetes (2013) · cites this paper as [98]
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- Authors
- Sheth, S. H., & Larson, R. J.
- Affiliations
- Dartmouth Institute for Health Policy and Clinical Practice (US)
- Dartmouth College (US)
- Corresponding author
- Sheth, Siddharth H
- ORCID
- Sheth, Siddharth H
- Venue
- BMC Infectious Diseases
- Published
- 2010-06-23
- Volume
- 10
- Issue
- 1
- Pages
- 183-183
- ISSN
- 1471-2334 (ISSN-L)
- PMC
- PMC2906460
- OpenAlex
- W2011652299
- Cited by
- 58
- References
- 59
- Citations by year
- 2023: 1 · 2021: 3 · 2020: 2 · 2019: 4 · 2018: 4 · 2017: 3 · 2016: 6 · 2015: 5 · 2014: 4 · 2013: 7 · 2012: 6
- FWCI
- 1.54
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- BMC Infectious Diseases (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- U.S. Department of Veterans Affairs
- Topics
- Health Sciences › Medicine › Emergency Medicine › HIV-related health complications and treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Keywords
- HIV-associated lipodystrophy, insulin-sensitizing drugs, rosiglitazone, pioglitazone, metformin, insulin resistance, lipid metabolism, triglycerides, HDL cholesterol, LDL cholesterol, body mass index, fat redistribution, drug safety, antiretroviral therapy adverse effects, waist-to-hip ratio, fasting insulin
- MeSH terms
- Rosiglitazone, Pioglitazone, Adult, Female, Humans, Hypoglycemic Agents, Insulin Resistance, Male, Metformin, Middle Aged, Randomized Controlled Trials as Topic, HIV-Associated Lipodystrophy Syndrome, Thiazolidinediones
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