One of the world’s most prescribed drugs, metformin is primarily used to treat type 2 diabetes. New research into its potential impact on other pathologies has made this molecule the hottest topic of the week. While several avenues appear promising, some results, including those of a recently published landmark study, are very disappointing (see infographic).
Disappointing results in breast cancer
The results of the clinical study MA.32, published in the JAMA “Point out that metformin is not effective against the most common types of breast cancer and that any off-label use of this drug in this setting should be halted,” said investigator Dr. Pamela Goodwin in a press release -Tanenbaum Research Institute, Toronto, Canada). The study involved 3,649 patients with hormone receptor positive or negative breast cancer who did not have diabetes. Patients were randomized to receive either placebo or metformin (850 mg twice daily) for 5 years. Among 2533 patients with hormone receptor-positive cancer, the incidence of invasive disease-free survival was 2.78 per 100 patient-years on metformin versus 2.74 on placebo (risk ratio [HR], 1.01; p=0.93). Among 1116 patients with hormone receptor-negative disease, the incidence of invasive disease-free survival was 3.58 on metformin versus 3.60 on placebo (HR 1.01; p=0.92).
The only potential bright spot: In a small subset of patients with HER2-positive disease (17% of total), 1.93 disease-free survival events were associated with metformin versus 3.05 events with placebo (HR, 0.64; p=0 .03) and 0.78 deaths per 100 patient-years were reported in the metformin group versus 1.43 in the placebo group (HR 0.54; p=0.04). The benefit was limited to patients with a C allele of the single nucleotide variant rs11212617. The results have yet to be confirmed by a randomized trial, but it’s possible that metformin “could be an additional treatment option for HER2-positive breast cancer,” said Dr. Goodwin.
Diabetic cancer patients
The results of recent studies in older cancer patients with type 2 diabetes are more encouraging. An analysis of 7,725 patients with lung, breast, prostate, pancreas, or colon cancer found that 38.5% of them (2,981 patients) had been prescribed metformin.  Patients on metformin had significantly better overall survival in unadjusted (HR 0.73; 95% CI 0.69-0.76; p<0.001) and adjusted (adjusted HR 0.77; 95% CI) models, IC 0.73 -0.81; p<0.001). The hazard ratios in subjects receiving metformin were 0.78 (95% CI, 0.69-0.88; p<0.001) for colorectal cancer, 0.77 (95% CI, 0.72-0.82; p<0.001) for lung cancer, 0.82 (95% CI). , 0.72-0.93; p<0.001) for pancreatic cancer and 0.74 (95% CI, 0.62-0.88; p=0.002) for prostate cancer.
Dampen antipsychotic-induced weight gain
Metformin has also shown promise in relieving antipsychotic-induced weight gain. New evidence-based recommendations from Ireland suggest that psychiatrists are quick to prescribe metformin to patients who gain more than 7% weight in the first month of antipsychotic treatment.  They also recommend prescribing metformin if weight gain is noted. The recommended starting dose is 500 mg twice daily with meals, increasing by 500 mg every 1 to 2 weeks until a target dose of 2000 mg/day is reached. With early intervention, the recommendations first suggest stabilizing weight gain or, if possible, reversing the excess weight. If weight gain is noticed, the goal is to lose at least 5% of the weight over the next 6 months.
Other studies suggest that metformin may have neuroprotective effects. According to a preprint study, the use of the antidiabetic could reduce the risk of Alzheimer’s in the general population. Taking metformin, which corresponds to a 6.75 mmol/mol (1.09%) reduction in HbA1c, was associated with a 4% reduced risk of Alzheimer’s disease in people without diabetes (p = 1.06 × 10-4 ).
Another systematic review and meta-analysis of longitudinal data showed that metformin may be associated with a greater reduction in the risk of neurodegenerative disease.  The pooled data showed that the relative risk associated with developing neurodegenerative disease in diabetics taking metformin was 0.77 (95% CI, 0.67-0.88). The effect was greater with longer use, with a relative risk of 0.29 (95% CI, 0.13-0.44) for those who had taken metformin for 4 years or more.
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