Endocrinology · USMLE Step 1 and Step 2

Metformin song

Metformin - Mechanism, Uses & Lactic Acidosis, as a song. Hear the short teaser here. The full song is on YouTube and Spotify.

Metformin

Full song on YouTube ↗Spotify ↗

Key points in this song10

Metformin is a biguanide that works primarily by inhibiting complex I of the mitochondrial electron transport chain in hepatocytes, decreasing hepatic gluconeogenesis and reducing fasting glucose.
It is the first-line pharmacologic agent for type 2 diabetes mellitus, preferred due to its weight-neutral or weight-reducing effect, low hypoglycemia risk when used as monotherapy, and cardiovascular benefit shown in the UKPDS trial.
The most feared adverse effect is lactic acidosis, a type B (non-hypoxic) lactic acidosis caused by accumulation of lactate from impaired mitochondrial oxidation.
Major contraindications include an eGFR below 30 mL/min/1.73m² (dose reduction required if eGFR 30–45), active or excessive alcohol use, acute heart failure, and hepatic impairment due to increased lactic acidosis risk.
Metformin must be held 48 hours before and after iodinated contrast administration in patients with eGFR below 60 to prevent contrast-induced nephropathy and subsequent drug accumulation.
Long-term metformin use causes vitamin B12 malabsorption by interfering with the calcium-dependent binding of the intrinsic factor–B12 complex in the terminal ileum, leading to megaloblastic anemia and peripheral neuropathy.
Unlike sulfonylureas and insulin, metformin does not stimulate insulin secretion and therefore does not cause hypoglycemia as monotherapy.
Metformin also increases peripheral glucose uptake and utilization in skeletal muscle and reduces intestinal glucose absorption as secondary mechanisms.
It is used off-label for polycystic ovary syndrome (PCOS) to improve insulin resistance, restore ovulation, and reduce androgen levels.
Metformin decreases triglycerides and LDL modestly and does not cause weight gain, distinguishing it from thiazolidinediones and insulin-secretagogues.