Dr Sharon Rees @reesprescribe
#metformin is the 1st line drug for type 2 diabetes mellitus (T2DM), and has been available in UK since 1958 and the US from the mid-1990s. It was discovered after French lilac extracts yielded clinical precursors trialled for flu and malaria, with incidental finding of lowering blood glucose #prescribing
Dr Sharon Rees @reesprescribe
#metformin is formed from 2 guanidines bonded to make biguanide. The brand name Glucophage = gluco (sugar) and phage (to eat) #prescribing
Dr Sharon Rees @reesprescribe
#metformin is licensed for prevention (Glucophage sustained release) and T2DM. Its off-license use is for PCOS, as metabolic disturbance linked to insulin resistance and hyperinsulinaemia. It is also unlicensed for 1st-line gestational diabetes mellitus #prescribing
Dr Sharon Rees @reesprescribe
The UK NICE guideline includes #metformin as adjunct to insulin for type I diabetes, if control needs to be improved and BMI >25 kg/m2 or >23 kg/m2 for South Asian/related populations #prescribing
Dr Sharon Rees @reesprescribe
#metformin is licensed for age 10+ (10–17 specialist use). Typical T2DM regimen is slow titration up to 1.5–2 g/day in divided doses. Can be used at all intensification stages and can be combined with other diabetic agents if tolerated #prescribing
Dr Sharon Rees @reesprescribe
Key kinetics: no metabolism/excreted whole and t ½ ~6.5 hours. Impaired clearance causes increases plasma concentration, so regular GFR measurement necessary, especially for elderly or initiation of new drug with renal effects. Avoid <30, caution eGFR <45 #prescribing
Dr Sharon Rees @reesprescribe
#metformin reduces hepatic glucose output and enhances muscle glucose uptake. This lowers blood glucose and insulin resistance. Its mechanism of action (MOA) is to activate activates liver kinase B, which regulates AMPK. AMPK inactivates gluconeogenic enzymes, so up-regulation of AMPK means less liver release of stored glycogen #prescribing
Dr Sharon Rees @reesprescribe
MOA of #metformin (cont): Action on gut wall to reduce intestinal glucose absorption may contribute to weight stabilisation/minor weight loss. These multiple actions on glucose pathways lead to lowered basal and post-meal glucose levels #prescribing
Dr Sharon Rees @reesprescribe
Long-term benefits of #metformin include being weight neutral, less hypoglycaemia risk, some cardiovascular protection and lowered all-cause mortality, all of which make #metformin an ideal 1st-line agent. Also, there is a low number of ‘mild’ drug-drug interactions with dolutegravir only ‘severe’ drug-drug interaction. #prescribing
Dr Sharon Rees @reesprescribe
#metformin is mostly well-tolerated. Common adverse drug reactions are GI, minimised by gentle titration and modified release, if GI intolerance (lowers local concentration). Altered gut wall function can cause low vitamin B12 and folate levels; this can cause/exacerbate peripheral neuropathy #prescribing
Dr Sharon Rees @reesprescribe
Interesting fact: #metformin is being trialled as ‘anti-aging’ agent. ‘Geroprotection’ is possibly from anti-hyperglycaemic effect, correction of blood lipids and general cardio protection. Metformin is mooted to protect from DNA damage via oxidative stress and less inflammation via modulation of the AMPK pathway #prescribing