Metformin

Metformin is a biguanide drug whose fundamental mechanism, according to Ray Peat, involves poisoning the mitochondria so that cells are forced to waste glucose by converting it to lactic acid. 2 Peat traced its lineage to the earlier drug phenformin, which was removed from the market in the 1950s and 60s because it was killing a very high proportion of users through lactic acidosis by rendering mitochondria unable to oxidize glucose—the very problem at the core of diabetes. 2 Metformin was introduced as a reputedly safer successor, but Peat noted that even on PubMed one can find over a hundred articles warning about its production of lactic acidosis, and that it occasionally causes dangerously fatal lactic acid edema. 2 He described the drug’s apparent benefits as “surprising and perverse,” acknowledging that while it does not kill everyone quickly, it works partly through this mitochondrial impairment, though it may also have some slightly protective anti-inflammatory effects. 2

Peat argued that metformin’s glucose-lowering action is a cosmetic masking of the underlying pathology. He explained that the drug lowers blood sugar in proportion to how fast it is wasting glucose, a process that takes the form of lactic acid production. 1 He situated this within a broader critique of the diabetes treatment paradigm, noting that the death rate from diabetes actually increased after the introduction of insulin, and that the myth that sugar causes diabetes was sustained to support treatments like insulin and later the “very toxic glucose waster” phenformin and its successor metformin. 2 Peat also expressed skepticism about metformin’s promotion as an anti-aging drug, suggesting its mechanism involves blocking protective functions and wasting cholesterol, which he saw as a perverse effect since cholesterol plays a protective role against the toxicity of polyunsaturated fats (PUFAs). 3

Georgi Dinkov has extended this critique with mechanistic precision, identifying metformin as an inhibitor of Complex I of the electron transport chain (ETC), which directly causes the lactic acidosis risk that is 30%+ lethal even with emergency treatment. 10 Dinkov has written that the drug’s touted benefits are largely attributed to its activation of the enzyme AMPK, a mechanism it shares with endurance exercise, fasting, and caloric restriction, which massively increases fatty acid oxidation (FAO). 2 He argues that this increased FAO worsens insulin sensitivity and that stopping metformin after prolonged use results in an exacerbation of diabetes pathology compared to patients who never took it, making the drug a “Trojan Horse” that masks symptoms while ruining systemic health. 2 Dinkov has also highlighted that metformin’s AMPK activation increases the expression of myostatin, the primary negative regulator of muscle growth, leading to muscle atrophy and a consequent tanking of the resting metabolic rate. 5

Danny Roddy and his co-hosts have observed the drug’s practical consequences in the health community, noting that metformin’s gut-wrecking side effects and its role as a mitochondrial complex blocker have led many to abandon it, though they predict it will cyclically return to vogue. 7 They have also pointed to the rationalization required to continue prescribing metformin when a patient’s fasting blood glucose nearly doubles, framing it as a dangerous failure to understand that the drug is not addressing the underlying insulin resistance. 4 Dinkov has further warned that metformin promotes cancer growth by increasing lactate and FAO, contrasting it with therapeutic anti-lactate measures like baking soda. 2