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Cited by 188Pharmacology and Obesity TreatmentDiabetes, Cardiovascular Risks, and LipoproteinsAdipokines, Inflammation, and Metabolic Diseases

Metformin reduces weight, centripetal obesity, insulin, leptin, and low-density lipoprotein cholesterol in nondiabetic, morbidly obese subjects with body mass index greater than 30

Glueck, C.J., Fontaine, R.N., Wang, Ping, Subbiah, M.T.R., Weber, K., Illig, E., Streicher, P., Sieve-Smith, Luann +3 more·2001·Metabolism
DOI 10.1053/meta.2001.24192
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Abstract

We studied 31 nondiabetic, habitually (> or =5 years) morbidly obese subjects (mean +/- SD body mass index [BMI] 43 +/- 8.7, median 43). Our specific aim was to determine whether metformin (2.55 g/d for 28 weeks) would ameliorate morbid obesity and reduce centripetal obesity; lipid and lipoprotein cholesterol, insulin, and leptin levels; and plasminogen activator inhibitor activity (PAI-Fx), risk factors for coronary heart disease (CHD). The patients were instructed to continue their prestudy dietary and exercise regimens without change. After 2 baseline visits 1 week apart, the 27 women and 4 men began receiving metformin, 2.55 g/d, which was continued for 28 weeks with follow-up visits at study weeks 5, 13, 21, and 29. Daily food intake was recorded by patients for 7 days before visits then reviewed with a dietitian. Kilocalories per day and per week were calculated. At each visit, fasting blood was obtained for measurement of lipid profile, insulin, leptin, and PAI-Fx. The mean +/- SD kilocalories consumed per day, 1,951 +/- 661 at entry, fell by week 29 to 1,719 +/- 493 (P =.014) but did not differ at weeks 5, 13, and 21 from that at week 29 (P >.2). Weight fell from 258 +/- 62 pounds at entry to 245 +/- 54 pounds at week 29 (P =.0001). Girth was reduced from 51.8 +/- 6.2 to 49.2 +/- 4.5 inches (P =.0001). Waist circumference fell from 44.0 +/- 6.4 inches to 41.3 +/- 5.9 (P =.0001). The waist/hip ratio fell from 0.85 +/- 0.09 to 0.84 +/- 0.09 (P =.04). Fasting serum insulin, 28 +/- 15 microU/mL at entry, fell to 21 +/- 11 microU/mL at week 29 (P =.0001), and leptin fell from 79 +/- 33 ng/mL to 55 +/- 27 ng/mL (P =.0001). On metformin, there were linear trends in decrements in weight, girth, waist circumference, waist/hip ratio, insulin, and leptin throughout the study period (P <.007). Low-density lipoprotein (LDL) cholesterol, 126 +/- 34 mg/dL at study entry, fell to 112 +/- 43 mg/dL at week 29 (P =.001), with a linear trend toward decreasing levels throughout (P =.036). By stepwise linear regression, the higher the entry weight, the larger the reduction in weight on metformin therapy (partial R(2) = 31%, P =.001). The greater the reduction in kilocalories consumed per day, the greater the decrease in weight on metformin therapy (partial R(2) = 15%, P =.011). The higher the waist/hip ratio at entry, the greater its reduction on metformin therapy (partial R(2) = 11%, P =.004). The higher the entry serum leptin, the greater its reduction on metformin therapy (partial R(2) = 29%, P =.002). The greater the reduction in insulin on metformin, the greater the reduction in leptin (partial R(2) = 8%, P =.03). The higher the entry PAI-Fx, the greater the reduction in PAI-Fx on metformin (partial R(2) = 43%, P =.0001). Metformin safely and effectively reduces CHD risk factors (weight, fasting insulin, leptin, LDL cholesterol, centripetal obesity) in morbidly obese, nondiabetic subjects with BMI > 30, probably by virtue of its insulin-sensitizing action.

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  • Many different mechanisms beyond glycemic control have been implicated in vascular protection induced by metformin, including improvements in the inflammatory pathway, coagulation, oxidative stress and glycation, endothelial dysfunction, haemostasis, insulin resistance, lipid profiles, and fat redistribution.

    “Many different mechanisms, beyond glycemic control, have been implicated in vascular protection induced by metformin such as improvements in the inflammatory pathway [86], coagulation [87], oxidative stress and glycation [88-92], endothelial dysfunction [88-90], haemostasis [88,91-93], insulin resistance improvement [94], lipid profiles [95,96], and fat redistribution [97,98].”

    From Metformin: An Old But Still the Best Treatment for Type 2 Diabetes (2013) · cites this paper as [95]

  • Metformin is associated with improvements in lipoprotein metabolism, including decreases in LDL-C, fasting and postprandial triglycerides, and free fatty acids.

    “Metformin is associated with improvements in lipoprotein metabolism, including decreases in LDL-C [95], fasting and postprandial TGs, and free fatty acids [106].”

    From Metformin: An Old But Still the Best Treatment for Type 2 Diabetes (2013) · cites this paper as [95]

  • Metformin may contribute to weight loss through reduction of leptin and ghrelin levels after glucose overload.

    “reduction of leptin [95] and ghrelin levels after glucose overload [96]”

    From Metformin: An Old But Still the Best Treatment for Type 2 Diabetes (2013) · cites this paper as [95]

  • Metformin may contribute to weight loss through reduction in gastrointestinal absorption of carbohydrates and insulin resistance.

    “The mechanisms by which metformin contributes to weight loss may be explained through the reduction in gastrointestinal absorption of carbohydrates and insulin resistance [95]”

    From Metformin: An Old But Still the Best Treatment for Type 2 Diabetes (2013) · cites this paper as [95]

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Authors
Glueck, C. J., Fontaine, R. N., Wang, P., Subbiah, M. T. R., Weber, K., Illig, E., Streicher, P., Sieve-Smith, L., Tracy, T. M., Lang, J. E., & McCullough, P.
Affiliations
Jewish Hospital (US)
ORCID
Venue
Metabolism
Publisher
Elsevier BV
Published
2001-07
Volume
50
Issue
7
Pages
856-861
ISSN
0026-0495 (ISSN-L)
DOI
10.1053/meta.2001.24192
OpenAlex
W1963764475
Cited by
188
References
33
Citations by year
2026: 2 · 2025: 6 · 2024: 4 · 2023: 6 · 2022: 12 · 2021: 4 · 2020: 5 · 2019: 7 · 2018: 7 · 2017: 14 · 2016: 12 · 2015: 11 · 2014: 15 · 2013: 10 · 2012: 12
FWCI
3.53
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Keywords
metformin, morbid obesity, weight loss, waist circumference, waist-to-hip ratio, insulin, leptin, LDL cholesterol, lipid profile, plasminogen activator inhibitor, coronary risk factors, dietary intake, physical activity
MeSH terms
Adult, Aged, Body Weight, Coronary Disease, Fasting, Female, Humans, Hypoglycemic Agents, Insulin, Cholesterol, LDL, Male, Metformin, Middle Aged, Obesity, Tissue Plasminogen Activator, Risk Factors, Body Mass Index, Leptin

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