Intranasal Insulin Reduces Body Fat in Men but not in Women
Open accessAbstract
Insulin acts in the central nervous system to reduce food intake and body weight and is considered a major adiposity signal. After intranasal administration, insulin enters the cerebrospinal fluid compartment and alters brain functions in the absence of substantial absorption into the blood stream. Here we report the effects of 8 weeks of intranasal administration of insulin (4 × 40 IU/day) or placebo to two groups of healthy human subjects (12 men and 8 women in each group). The insulin-treated men lost 1.28 kg body wt and 1.38 kg of body fat, and their waist circumference decreased by 1.63 cm. Plasma leptin levels dropped by an average of 27%. In contrast, the insulin-treated women did not lose body fat and gained 1.04 kg body wt due to a rise in extracellular water. Our results provide a strong, first confirmation in humans that insulin acts as a negative feedback signal in the regulation of adiposity and point to a differential sensitivity to the catabolic effects of insulin based on sex.
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Intranasal insulin reduces body fat in men but not in women.
“Indeed, intranasal insulin—which reaches the brain directly along olfactory perivascular channels—reduces body fat in men but not in women [33].”
From Sex differences in metabolic homeostasis, diabetes, and obesity (2015) · cites this paper as [33]
The study summary reports that after eight weeks of intranasal insulin, healthy men lost body fat while healthy women did not. The paper also says intranasal insulin reaches the brain, but our copy does not specify the olfactory perivascular channels named in the citing sentence. (LLM, conf=0.87)
Experimental — accuracy not yet measuredExperimental studies suggest considerable sex differences in brain insulin sensitivity.
“Of note, experimental studies suggest considerable sex differences in brain insulin sensitivity.”
From Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase (2023) · cites this paper as [26]
Daily nasal insulin administration over 8 weeks reduced body weight and body fat content only in men, whereas women showed no reduction in body adiposity.
“Nevertheless, daily nasal insulin administration over 8 weeks reduced body weight and body fat content only in men, whereas women showed no reduction in body adiposity26.”
From Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase (2023) · cites this paper as [26]
Delivery schedules synced to food intake might be necessary for the catabolic impact of IN insulin to emerge.
“suggesting that delivery schedules synced to food intake 39,42,44,47 might be necessary for the catabolic impact of IN insulin to emerge.”
From Intranasal insulin (2021) · cites this paper as [42]
In healthy, normal-weight humans, IN insulin administration for 8 weeks at 4 × 40 IU per day reduced body weight and body fat content in men, but not women.
“In healthy, normal-weight humans, IN insulin administration for 8 weeks (4 × 40 IU day -1 ) reduced body weight and body fat content in men, but not women.”
From Intranasal insulin (2021) · cites this paper as [42]
The loss of body fat in men after 8-week IN insulin was associated with a 27% reduction in circulating leptin concentrations.
“The loss of body fat in the men was associated with a 27% reduction in the circulating concentrations of leptin.”
From Intranasal insulin (2021) · cites this paper as [42]
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Self-citation
- Authors
- Hallschmid, M., Benedict, C., Schultes, B., Fehm, H.-L., Born, J., & Kern, W.
- Affiliations
- University of Lübeck (DE)
- Institute of Neuroendocrinology, University of Lübeck, Lübeck, Germany
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2004-11-01
- Volume
- 53
- Issue
- 11
- Pages
- 3024-3029
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2157247104
- Cited by
- 281
- References
- 32
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 7 · 2023: 8 · 2022: 10 · 2021: 14 · 2020: 9 · 2019: 12 · 2018: 20 · 2017: 11 · 2016: 16 · 2015: 17 · 2014: 10 · 2013: 24 · 2012: 21
- FWCI
- 3.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- intranasal insulin, fat loss, sex differences, leptin, waist circumference, plasma leptin, extracellular water, weight loss
- MeSH terms
- Adipose Tissue, Administration, Intranasal, Body Weight, Extracellular Space, Female, Humans, Insulin, Male, Placebos, Reference Values, Sex Characteristics, Body Mass Index
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