In the news: metformin



Metformin, one of the most commonly prescribed medical drugs in the world, is mainly used for traiter type 2 diabetes. week. While several avenues appear promising, some results, including those of a recently published landmark trial, are highly disappointing (see infographic).

Disappointing results in breast cancer

The results of the clinical trial MA.32 published in the JAMA[1] “indicate 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 discontinued,” researcher Dr. Pamela said in a news release. Goodwin, director and medical oncologist (Lunenfeld – 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 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 with metformin versus 2.74 with placebo (hazard ratio [HR], 1.01; p = 0.93). Among 1,116 patients with hormone receptor-negative disease, the incidence of invasive disease-free survival was 3.58 with metformin versus 3.60 with placebo (HR, 1.01; P=.92).

The only potential bright spot: Among a small subset of patients who had HER2-positive disease (17% overall), 1.93 disease-free survival events were associated with metformin versus 3.05 events with placebo (HR, 0.64; p=0.03), with 0.78 deaths per 100 patient-years 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 need to be confirmed by a randomized trial, but it is possible that metformin “may be an additional treatment option for HER2-positive breast cancer,” said Dr. Goodwin.

Diabetic cancer patients

The results of recent studies in older patients with cancer and type 2 diabetes are more encouraging. An analysis of 7,725 patients with lung, breast, prostate, pancreatic, or colorectal cancer reported that 38.5% of them (2,981 patients) had been prescribed metformin. [2] Metformin-treated patients had significantly better overall survival in unadjusted (HR, 0.73; 95% CI, 0.69-0.76; P < .001) and adjusted models (adjusted HR, 0.77; CI 95%. CI, 0.73-0.81; p<0.001). Hazard ratios in persons who received metformin were 0.78 (95% CI, 0.69-0.88; P<.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.

Attenuate antipsychotic-induced weight gain

Metformin has also shown promise in mitigating antipsychotic-induced weight gain. New evidence-based recommendations from Ireland suggest that psychiatrists promptly prescribe metformin to patients who have more than a 7% increase in their baseline weight during the first month of antipsychotic treatment. [3] They also recommend the prescription of metformin when weight gain is established. The suggested starting dose is 500 mg twice daily with food, with increases of 500 mg every 1 to 2 weeks until a target dose of 2000 mg/day is reached. In the case of early intervention, the recommendations propose first to stabilize the weight gained or, if possible, to reverse the overweight. When weight gain is established, the goal is to lose at least 5% of the weight in the next 6 months.

neuroprotective effects?

Other studies suggest that metformin may have neuroprotective effects. According to a preliminary study, the use of the antidiabetic could reduce the risk of Alzheimer’s disease in the general population.[4] The use of metformin, equivalent to a 6.75 mmol/mol (1.09%) reduction in HbA1c, was associated with a 4% lower 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. [5] Pooled data showed that the relative risk associated with the development of neurodegenerative diseases was 0.77 (95% CI, 0.67-0.88) in diabetic patients taking metformin. The effect was greater with prolonged use, with a relative risk of 0.29 (95% CI, 0.13-0.44) for those who had been taking metformin for 4 years or more.

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