Metformin, a medication primarily used to treat type 2 diabetes, has garnered attention for its potential off-label benefits, particularly for women experiencing menopause. This article delves into the role of metformin in managing weight, improving metabolic health, and addressing other health concerns during menopause.
Understanding Menopause and Its Impact on Blood Sugar
Menopause, characterized by the decline of estrogen and progesterone, brings about various physiological changes. Estrogen plays a crucial role in insulin regulation, and its decline during menopause can lead to insulin resistance and elevated blood sugar levels. This hormonal shift increases the risk of cardiovascular disease, abdominal fat accumulation, high blood pressure, and high cholesterol.
Dr. Kathleen Jordan, Chief Medical Officer at Midi, emphasizes the association between estrogen and progesterone depletion during midlife and worsening insulin sensitivity. Elevated blood sugars, in turn, contribute to poor cellular repair, increased inflammation, and cardiovascular disease, the leading cause of death in women.
Metformin: A Potential Tool for Managing Menopause-Related Issues
Metformin, approved by the FDA in 1995 for treating type 2 diabetes, has been found to offer additional benefits beyond blood sugar control. It is often prescribed off-label during menopause to:
- Treat polycystic ovary syndrome (PCOS)
- Manage obesity and facilitate mild weight loss
- Reduce risk factors for stroke, cardiovascular disease, and certain cancers
- Stave off cognitive decline
- Slow aging
Research suggests that metformin can extend lifespan by improving insulin sensitivity, reducing inflammation, and protecting cognitive function.
Read also: Berberine and Metformin
The Science Behind Metformin's Longevity Benefits
Metformin's anti-aging properties are linked to its ability to reduce inflammation, improve insulin sensitivity, and prevent DNA damage. Telomeres, protective caps at the ends of DNA strands, tend to break down over time, making DNA vulnerable to disease. Metformin has been shown to protect telomeres, reduce cellular death, and ultimately exert an anti-aging effect.
A study in Nature assessed the gene expression of 79 tissues and organs, revealing that metformin impacted age-related pathways and improved DNA repair, which is related to longer lifespan.
Metformin and Weight Loss
Evidence suggests that metformin can contribute to weight loss, particularly in individuals with prediabetes, obesity, or those taking antipsychotic medications.
- Diabetes Prevention Program (DPP): In this study, participants with prediabetes experienced an average weight loss of 2.1 kg in the metformin group compared to 0.1 kg in the placebo group over 2.8 years.
- Biguanides and Prevention of the Risks in Obesity (BigPRO): After 12 months, participants receiving metformin experienced a significantly better effect on weight compared to placebo.
- Real-World Study: Patients with obesity and no diabetes experienced a mean weight loss of 5.8 kg in the metformin group compared to a gain of 0.8 kg in the control group.
A meta-analysis of 21 trials found that metformin reduced BMI in patients with obesity, particularly those with a BMI greater than 35 kg/m2, at doses higher than 1,500 mg/day for at least 6 months.
Metformin's Effectiveness in Diabetes Prevention in Postmenopausal Women
Global Prediabetes and Diabetes Prevalence reports indicate that the prevalence of prediabetes has more than doubled over the past two decades. For women going through menopause, the situation is even more serious. From the age of 70 to 74, the rates of diabetes in women surpass those in men. This may be because menopause reduces levels of protective hormones like estrogen and progesterone, which help guard against type 2 diabetes (T2D). Metformin's effectiveness seems to increase when combined with lifestyle changes, such as diet and exercise.
Read also: Ingredients in Menopause Gummies
Metformin's Role in Polycystic Ovary Syndrome (PCOS)
In women with polycystic ovary syndrome, metformin therapy has been shown to increase ovulation, menstrual frequency, fertility, and rates of live birth. A meta-analysis comparing orlistat with metformin in women with polycystic ovary syndrome found that both had similar favorable effects on BMI, with a mean decrease in BMI of 3.4 to 4.55 with metformin, and 4.48 to 5.7 with orlistat (difference −0.65%, 95% CI −2.03 to 0.73).
Potential Mechanisms of Action
The mechanisms underlying metformin's effects on body weight extend beyond its insulin-sensitizing properties. These include:
- Appetite suppression through increased secretion of glucagon-like peptide 1 and peptide YY
- Alteration of the gut microbiome
- Induced expression and secretion of growth-differentiating factor 15, which reduces food intake, body mass, fasting insulin, and glucose intolerance
Pros and Cons of Metformin During Menopause
When considering metformin for menopause, it's crucial to weigh the potential benefits against the possible drawbacks.
Pros:
- Improved insulin levels and metabolic health
- Improved heart health
- Reduced risk of certain cancers
- Potential for longer lifespan
- Inexpensive (metformin is generic)
Cons:
- Potential side effects, including nausea, gas, and diarrhea
- May have contraindications
- Risk of blood glucose levels dropping too low
Who Should Consider Metformin During Menopause?
Metformin might be a suitable option for women experiencing insulin resistance or prediabetes, those with a family history of diabetes, or those experiencing metabolic shifts like weight gain during menopause.
Alternatives and Complementary Approaches
HRT vs. Metformin
Hormone replacement therapy (HRT) is an alternative to metformin, particularly for managing hot flashes, night sweats, and genitourinary symptoms. Research suggests that individualized HRT can promote healthier body composition, decrease total fat mass and abdominal fat, and improve insulin resistance and blood lipid levels.
Read also: Facial Hair Growth During Menopause
Lifestyle Changes
Lifestyle modifications can also improve insulin levels and alleviate menopause-related symptoms. These include:
- Healthy Diet: A diet rich in fruits, vegetables, healthy fats, and lean proteins
- Regular Exercise: Physical activity reduces inflammation, stimulates human growth hormone levels, and aids DNA repair.
- Adequate Sleep: Aim for seven hours of quality sleep per night.
- Supplements: NAD, vitamin D, vitamin K, magnesium, and omega-3s may help with menopause symptoms and healthy aging.
Metformin and Ovariectomized Rats: A Model for Menopause
Studies on ovariectomized rats, a model for menopause, have shown that metformin can prevent early metabolic dysfunction. Ovariectomized rats exhibit increased body mass, insulin resistance, and changes in lipid profiles, mimicking the effects of estrogen deficiency during menopause.
Metformin treatment in these rats diminished approximately 50% of the mass gain, reduced serum and hepatic triglyceride levels, and increased the levels of phosphorylated AMP-activated protein kinase (pAMPK) in the liver.
Mechanism of Metformin for Weight Loss
An "anti-hunger" molecule produced after vigorous exercise is responsible for the moderate weight loss caused by the diabetes medication metformin, according to a new study in mice and humans. The finding, made jointly by researchers at Stanford Medicine and at Harvard Medical School, further cements the critical role the molecule, called lac-phe, plays in metabolism, exercise and appetite. The researchers found that obese laboratory mice given metformin had increased levels of lac-phe in their blood. They saw significant increases in the levels of lac-phe in people after metformin compared with their levels before treatment.
Safety and Side Effects
Metformin is generally safe when used appropriately. Common side effects include gastrointestinal issues like diarrhea, nausea, and abdominal discomfort. Serious adverse events are rare, but the main contraindication is severe renal impairment.
Chronic metformin use has been associated with a decrease in serum vitamin B12 levels, which can be addressed with supplementation.
Cost-Effectiveness
Metformin is widely available and inexpensive, making it an accessible option for many individuals.