Trial reportThe Journal of clinical endocrinology and metabolism2016
Metformin Increases Cortisol Regeneration by 11βHSD1 in Obese Men With and Without Type 2 Diabetes Mellitus.
Trial report in The Journal of clinical endocrinology and metabolism, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
What it found
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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
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.
- Individual differences in glucocorticoid regulation: Does it relate to disease risk and resilience?Frontiers in neuroendocrinology · 2020Pooled it
- Effects of Obesity and Insulin on Tissue-Specific Recycling Between Cortisol and Cortisone in Men.The Journal of clinical endocrinology and metabolism · 2021Trial
- Diet-induced weight loss alters hepatic glucocorticoid metabolism in type 2 diabetes mellitus.European journal of endocrinology · 2020Trial
- Osteoporosis in Adrenal Insufficiency: Could Metformin be Protective?Indian journal of clinical biochemistry : IJCB · 2025Review
- Combination of Metformin and Epigallocatechin-3-Gallate Lowers Cortisol, 11β-Hydroxysteroid Dehydrogenase Type 1, and Blood Glucose Levels in Sprague Dawley Rats with Obesity and Diabetes.Journal of obesity & metabolic syndrome · 2024Article
- ATP-binding cassette family C member 1 constrains metabolic responses to high-fat diet in male mice.The Journal of endocrinology · 2024Article
- Uncovering antiobesity-related hypertension targets and mechanisms of metformin, an antidiabetic medication.Bioengineered · 2021Article
- Lower Renal Function Is Associated With Derangement of 11-Journal of the Endocrine Society · 2018Article
- Quantification of 11β-hydroxysteroid dehydrogenase 1 kinetics and pharmacodynamic effects of inhibitors in brain using mass spectrometry imaging and stable-isotope tracers in mice.Biochemical pharmacology · 2018Article
- Neonatal overfeeding induced glucocorticoid overexposure accelerates hepatic lipogenesis in male rats.Nutrition & metabolism · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
contextThe mechanism of action of metformin remains unclear. Given the regulation of the cortisol-regenerating enzyme 11βhydroxysteroid dehydrogenase 1 (11βHSD1) by insulin and the limited efficacy of selective 11βHSD1 inhibitors to lower blood glucose when co-prescribed with metformin, we hypothesized that metformin reduces 11βHSD1 activity.
objectiveTo determine whether metformin regulates 11βHSD1 activity in vivo in obese men with and without type 2 diabetes mellitus.
designDouble-blind, randomized, placebo-controlled, crossover study.
settingA hospital clinical research facility.
participantsEight obese nondiabetic (OND) men and eight obese men with type 2 diabetes (ODM).
interventionParticipants received 28 days of metformin (1 g twice daily), placebo, or (in the ODM group) gliclazide (80 mg twice daily) in random order. A deuterated cortisol infusion at the end of each phase measured cortisol regeneration by 11βHSD1. Oral cortisone was given to measure hepatic 11βHSD1 activity in the ODM group. The effect of metformin on 11βHSD1 was also assessed in human hepatocytes and Simpson-Golabi-Behmel syndrome adipocytes.
main outcome measuresThe effect of metformin on whole-body and hepatic 11βHSD1 activity.
resultsWhole-body 11βHSD1 activity was approximately 25% higher in the ODM group than the OND group. Metformin increased whole-body cortisol regeneration by 11βHSD1 in both groups compared with placebo and gliclazide and tended to increase hepatic 11βHSD1 activity. In vitro, metformin did not increase 11βHSD1 activity in hepatocytes or adipocytes.
conclusionsMetformin increases whole-body cortisol generation by 11βHSD1 probably through an indirect mechanism, potentially offsetting other metabolic benefits of metformin. Co-prescription with metformin should provide a greater target for selective 11βHSD1 inhibitors.
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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 OpenQuestion graph.