How does Metformin (metformin hydrochloride) induce weight loss?

From the Guidelines

Metformin leads to weight loss through several mechanisms, including decreased inflammation, increased insulin and leptin sensitivity, and decreased hunger and ghrelin levels, with approximately 3% weight loss and 25% to 50% of participants achieving at least 5% weight loss, as seen in the most recent study from 2023 1.

Mechanisms of Weight Loss

The weight loss effects of metformin can be attributed to several factors, including:

• Decreased hunger and ghrelin levels, especially with twice-daily dosing 1
• Increased insulin and leptin sensitivity, which helps regulate blood sugar and reduces fat storage
• Decreased inflammation, which can contribute to weight gain and metabolic disorders
• Changes in gut bacteria composition to favor beneficial bacteria that help with weight management

Clinical Evidence

The most recent study from 2023 found that metformin was associated with approximately 3% weight loss, and approximately 25% to 50% of participants achieved at least 5% weight loss 1. The study also found that doses of metformin greater than 1500 mg are associated with the greatest weight loss. Another study from 2022 found that metformin may be beneficial for patients with prediabetes, especially those with a higher baseline fasting glucose and A1C 1.

Clinical Implications

The use of metformin for weight loss should be considered in patients with prediabetes, especially those with a higher baseline fasting glucose and A1C, as well as those with a history of gestational diabetes mellitus 1. Additionally, metformin may be beneficial for patients who need to lose weight, especially those with a BMI ≥35 kg/m2. However, it is essential to monitor patients for potential side effects, such as gastrointestinal issues, and to consider periodic measurement of vitamin B12 levels in metformin-treated patients, especially in those with anemia or peripheral neuropathy 1.

From the FDA Drug Label

Mean change in body weight from baseline to week 29 was -1.4 lbs and -2. 4 lbs in the metformin hydrochloride tablets and placebo arms, respectively. Mean change in body weight from baseline to week 29 was 0.9 lbs, -0.7 lbs, and -8. 4 lbs in the metformin hydrochloride tablets /glyburide, glyburide, and metformin hydrochloride tablets arms, respectively. Mean change in body weight from baseline to week 16 was -3.3 lbs and -2. 0 lbs in the metformin hydrochloride tablets and placebo arms, respectively. Mean change in body weight from baseline to week 24 was 0.9 lbs, 1.1 lbs and 0.9 lbs, respectively.

Metformin leads to weight loss due to a decrease in body weight, as shown in the studies. The exact mechanism is not explicitly stated in the drug label, but the data suggests that metformin is associated with a reduction in body weight compared to placebo or other treatments.

• Key points:
  • Metformin hydrochloride tablets resulted in a mean change in body weight of -1.4 lbs to -8.4 lbs in different studies.
  • The placebo arm resulted in a mean change in body weight of -2.4 lbs to 0.9 lbs in different studies.
  • The combination of metformin hydrochloride tablets and glyburide resulted in a mean change in body weight of 0.9 lbs. 2

From the Research

Mechanisms of Metformin-Induced Weight Loss

• Metformin decreases appetite and opposes unfavorable fat storage in peripheral tissues, leading to weight loss 3.
• The effect of metformin on appetite is likely to be multifactorial, involving changes in hypothalamic physiology, including leptin and insulin sensitivity 3.
• Metformin also affects gastrointestinal physiology and circadian rhythm, regulating food intake, fat oxidation, and storage in liver, skeletal muscle, and adipose tissue 3, 4.
• Modulation of hypothalamic appetite regulatory centers, alteration in the gut microbiome, and reversal of consequences of aging are also proposed mechanisms for metformin-associated weight loss 4.

Clinical Evidence for Metformin-Induced Weight Loss

• Metformin induces modest weight loss in overweight and obese individuals at risk for diabetes 3, 5.
• A study of 154 consecutive patients with a body mass index ≥27 kg/m(2) found that metformin treatment resulted in a mean weight loss of 5.8±7.0 kg (5.6±6.5%) over 6 months 5.
• Patients with severe insulin resistance lost significantly more weight than insulin-sensitive patients 5.
• Weight loss with metformin is directly related to decreased insulin secretory demand and increased compensatory insulin secretion, with greater effects seen with intensive lifestyle intervention 6.

Comparison with Other Weight Loss Interventions

• A 3-month randomized prospective open-label study found that orlistat resulted in greater weight loss and improvement in body composition compared to metformin, while metformin resulted in a reduction of android fat 7.
• Both metformin and orlistat produced comparable improvements in insulin/glucose homeostasis, with greater benefits seen in insulin-resistant women 7.