ArticleDiabetology & metabolic syndrome2019
Low dose chloroquine decreases insulin resistance in human metabolic syndrome but does not reduce carotid intima-media thickness.
Article in Diabetology & metabolic syndrome, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Systematic review and meta-analysis of the safety of chloroquine and hydroxychloroquine from randomized controlled trials on malarial and non-malarial conditions.Systematic reviews · 2021Pooled it
- Trial
- Ultrasound Core Laboratory for the Household Air Pollution Intervention Network Trial: Standardized Training and Image Management for Field Studies Using Portable Ultrasound in Fetal, Lung, and Vascular Evaluations.Ultrasound in medicine & biology · 2021Trial
- The contrasting effects of two antimalarial drugs on insulin secretion.Cellular and molecular life sciences : CMLS · 2025Article
- Hydroxychloroquine as an Adjunct Therapy for Diabetes in Pregnancy.International journal of molecular sciences · 2024Review
- Native High-Density Lipoproteins (HDL) with Higher Paraoxonase Exerts a Potent Antiviral Effect against SARS-CoV-2 (COVID-19), While Glycated HDL Lost the Antiviral Activity.Antioxidants (Basel, Switzerland) · 2021Article
- Repurposing Chloroquine Against Multiple Diseases With Special Attention to SARS-CoV-2 and Associated Toxicity.Frontiers in pharmacology · 2021Review
- COVID-19 and diabetes mellitus: from pathophysiology to clinical management.Nature reviews. Endocrinology · 2021Review
- Repurposing New Use for Old Drug Chloroquine against Metabolic Syndrome: A Review on Animal and Human Evidence.International journal of medical sciences · 2021Review
- Chronic inflammatory diseases, myocardial function and cardioprotection.British journal of pharmacology · 2020Review
- The past, present and future of RNA respiratory viruses: influenza and coronaviruses.Pathogens and disease · 2020Review
- Heart failure and diabetes: role of ATM.Current opinion in pharmacology · 2020Review
- Are the Clinical Presentations (Phenotypes) of Gitelman's and Bartter's Syndromes Gene Mutations Driven by Their Effects on Intracellular pH, Their "pH" Enotype?International journal of molecular sciences · 2020Review
- The Effects of Chloroquine and Hydroxychloroquine on ACE2-Related Coronavirus Pathology and the Cardiovascular System: An Evidence-Based Review.Function (Oxford, England) · 2020Article
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15 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundMetabolic syndrome, an obesity-related condition associated with insulin resistance and low-grade inflammation, leads to diabetes, cardiovascular diseases, cancer, osteoarthritis, and other disorders. Optimal therapy is unknown. The antimalarial drug chloroquine activates the kinase ataxia telangiectasia mutated (ATM), improves metabolic syndrome and reduces atherosclerosis in mice. To translate this observation to humans, we conducted two clinical trials of chloroquine in people with the metabolic syndrome.
methodsEligibility included adults with at least 3 criteria of metabolic syndrome but who did not have diabetes. Subjects were studied in the setting of a single academic health center. The specific hypothesis: chloroquine improves insulin sensitivity and decreases atherosclerosis. In Trial 1, the intervention was chloroquine dose escalations in 3-week intervals followed by hyperinsulinemic euglycemic clamps. Trial 2 was a parallel design randomized clinical trial, and the intervention was chloroquine, 80 mg/day, or placebo for 1 year. The primary outcomes were clamp determined-insulin sensitivity for Trial 1, and carotid intima-media thickness (CIMT) for Trial 2. For Trial 2, subjects were allocated based on a randomization sequence using a protocol in blocks of 8. Participants, care givers, and those assessing outcomes were blinded to group assignment.
resultsFor Trial 1, 25 patients were studied. Chloroquine increased hepatic insulin sensitivity without affecting glucose disposal, and improved serum lipids. For Trial 2, 116 patients were randomized, 59 to chloroquine (56 analyzed) and 57 to placebo (51 analyzed). Chloroquine had no effect on CIMT or carotid contrast enhancement by MRI, a pre-specified secondary outcome. The pre-specified secondary outcomes of blood pressure, lipids, and activation of JNK (a stress kinase implicated in diabetes and atherosclerosis) were decreased by chloroquine. Adverse events were similar between groups.
conclusionsThese findings suggest that low dose chloroquine, which improves the metabolic syndrome through ATM-dependent mechanisms in mice, modestly improves components of the metabolic syndrome in humans but is unlikely to be clinically useful in this setting.
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