Metformin

Metformin is a real drug with real effects, real benefits, and a real, dose-dependent risk of a life-threatening complication that the establishment downplays.

Metformin lowers blood sugar. The evidence here is consistent across dozens of trials, mostly funded by manufacturers of drugs tested on top of metformin, not by independent bodies. A 2007 study showed it drops HbA1c by about 1.4 percentage points (from 9.3% to 7.9%) [3]. A 2003 trial found a combination pill with glyburide dropped A1c by 2.27 percentage points from a baseline of 8.78% [11]. It works. The question is the net effect on the whole person.

The serious risk is metformin-associated lactic acidosis (MALA). This is not a theoretical concern. A 2018 study of 75,413 patients found the risk of hospitalization for acidosis only rose significantly when kidney function dropped below an eGFR of 30 [17]. But a 2016 case series of 16 MALA patients reported a 31% mortality rate, with lactate levels averaging 9.58 mmol/L [21]. A 2025 Thai cohort of 143 patients with MALA and acute kidney injury found an overall in-hospital mortality of 20.3%, with kidney replacement therapy cutting that risk by about 70% compared to supportive care alone [43]. The mechanism is clear: metformin accumulates when kidneys cannot clear it, and the resulting acidosis kills roughly 1 in 5 to 1 in 3 of those who develop it. The establishment's framing of "rare but serious" hides the fact that when it happens, it is a medical emergency with a high death rate.

The evidence also shows metformin may reduce cancer risk. A 2010 study found metformin use was associated with an over 80% reduction in hepatocellular carcinoma risk [16]. A 2015 review found it lowered the Ki-67 proliferation index in endometrial cancer by 16.9% over 20 days [44]. These are promising signals, but they come from observational studies and small presurgical trials, not from large randomized trials designed to prove cancer prevention. The mechanism—lowering insulin and IGF-1—is plausible, but the evidence is not yet definitive.

My call: metformin is a useful drug for lowering blood sugar in type 2 diabetes, but it carries a real risk of fatal lactic acidosis that is concentrated in patients with kidney impairment, acute illness, or alcohol abuse. The benefit in cancer prevention is suggestive but unproven. The evidence base is dominated by industry-funded add-on trials, not independent long-term safety studies. Confidence: moderate for glycemic benefit, low for cancer prevention, high for the existence and severity of MALA risk.