ArticleAging2018
Metformin reduces glucose intolerance caused by rapamycin treatment in genetically heterogeneous female mice.
Article in Aging, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 39 citations in OpenAlex.
- Calorie restriction mimetics against aging and inflammation.Biogerontology · 2025Review
- Dapagliflozin combined with metformin improves blood glucose, bone metabolism and bone mineral density in elderly patients with type 2 diabetes mellitus complicated with osteoporosis.The Kaohsiung journal of medical sciences · 2025Article
- eNODAL: an experimentally guided nutriomics data clustering method to unravel complex drug-diet interactions.Briefings in bioinformatics · 2024Article
- Combinatorial interventions in aging.Nature aging · 2023Review
- Metformin protects against pulmonary hypertension-induced right ventricular dysfunction in an age- and sex-specific manner independent of cardiac AMPK.American journal of physiology. Heart and circulatory physiology · 2023Article
- Dietary Walnuts Preserve Aspects of Health Span and Alter the Hippocampal Lipidome in Aged High-Fat Diet-Fed Mice.International journal of molecular sciences · 2023Article
- Effect of Sirolimus/Metformin Co-Treatment on Hyperglycemia and Cellular Respiration in BALB/c Mice.International journal of molecular sciences · 2023Article
- Rapamycin treatment early in life reprograms aging: hyperfunction theory and clinical practice.Aging · 2022Article
- Rapamycin/metformin co-treatment normalizes insulin sensitivity and reduces complications of metabolic syndrome in type 2 diabetic mice.Aging cell · 2022Article
- Metformin Can Enhance the Inhibitory Effect of Olaparib in Bladder Cancer Cells.Disease markers · 2022Article
- Anti-aging: senolytics or gerostatics (unconventional view).Oncotarget · 2021Review
- Article
- Sarcopenia: What Is the Origin of This Aging-Induced Disorder?Frontiers in genetics · 2021Review
- Combining a High Dose of Metformin With the SIRT1 Activator, SRT1720, Reduces Life Span in Aged Mice Fed a High-Fat Diet.The journals of gerontology. Series A, Biological sciences and medical sciences · 2020Article
- Post-Transplantation Diabetes Mellitus.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2020Review
- Brain Protein Synthesis Rates in the UM-HET3 Mouse Following Treatment With Rapamycin or Rapamycin With Metformin.The journals of gerontology. Series A, Biological sciences and medical sciences · 2020Article
- Rapamycin for longevity: opinion article.Aging · 2019Article
- Fasting and rapamycin: diabetes versus benevolent glucose intolerance.Cell death & disease · 2019Review
- Taming expectations of metformin as a treatment to extend healthspan.GeroScience · 2019Review
- The Cutting Edge: The Role of mTOR Signaling in Laminopathies.International journal of molecular sciences · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
The use of rapamycin to extend lifespan and delay age-related disease in mice is well-established despite its potential to impair glucose metabolism which is driven partially due to increased hepatic gluconeogenesis. We tested whether a combination therapeutic approach using rapamycin and metformin could diminish some of the known metabolic defects caused by rapamycin treatment in mice. In genetically heterogeneous HET3 mice, we found that chronic administration of encapsulated rapamycin by diet caused a measurable defect in glucose metabolism in both male and female mice as early as 1 month after treatment. In female mice, this defect was alleviated over time by simultaneous treatment with metformin, also by diet, such that females treated with both drugs where indistinguishable from control mice during glucose tolerance tests. While rapamycin-mediated glucose intolerance was unaffected by metformin in males, we found metformin prevented rapamycin-mediated reduction in insulin and leptin concentrations following 9 months of co-treatment. Recently, the Interventions Testing Program showed that mice treated with metformin and rapamycin live at least as long as those treated with rapamycin alone. Together, our data provide compelling evidence that the pro-longevity effects of rapamycin can be uncoupled from its detrimental effects on metabolism through combined therapeutic approaches.
Indexed as
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What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.