Episode 372: 383. What is the GFR at which we stop metforin?

Metformin while not necessarily first line therapy for diabetes depending on the patients co-morbid conditions it is certainly highly ranked on the list of medications!

I know often metformin is stopped while coming into the hospital for fear of potentially lactic acidosis or an increase in AKI with contrast studies however this ‘belief’ is largely based on myth and misconception. Metformin's contraindications should be contraindicated - PMC

I also know that often metformin is held at discharge if the patients GFR is near or around 30

However, two new studies.

Stopping Versus Continuing Metformin in Patients With Advanced CKD: A Nationwide Scottish Target Trial Emulation Study - ClinicalKey

4,278 Scottish residents with a diagnosis of type 2 diabetes were identified as prevalent metformin users with incident CKD stage 4. (it was stopped when they reached CKD 5)

Results:

Compared with continuing metformin, stopping metformin was associated with a lower 3-year survival (63.7% [95% CI, 60.9-66.6] vs 70.5% [95% CI, 68.0-73.0]; HR, 1.26 [95% CI, 1.10-1.44]) (THAT WOULD BE ROUGHLY A NNT OF 14)

Interestingly the thing we think metformin prevents (MACE) was the same in both groups (HR, 1.05 [95% CI, 0.88-1.26]).

Could it be possible that metformin saves your life on some other mechanism that we don’t totally understand??

Discontinuing metformin was associated with a higher risk of death from respiratory diseases (HR, 1.51 [95% CI, 1.06-2.12]) MAYBE THAT IS THE SECRET!?

Trial 2

Clinical outcomes following discontinuation of metformin in patients with type 2 diabetes and advanced chronic kidney disease in Hong Kong: a territory-wide, retrospective cohort and target trial emulation study - ScienceDirect

33,586 metformin users with new-onset eGFR < 30 ml/min/1.73 m2 were included in the study and 7500 (22.3%) of whom discontinued metformin within 6 months whereas 26,086 (77.7%) continued use of metformin. They were followed for a median duration of 3.8 (IQR: 2.2–6.1) years,

This time, those in which metformin was discontinued had higher risk of MACE (weighted and adjusted HR = 1.40, 95% CI: 1.29–1.52),

AND once again if you stopped the metformin you had a higher incidence of death (HR = 1.22, 1.18–1.27).

BUT get this, if you stopped the metformin you had higher rates of progression to END STAGE KIDNEY DISEASE (HR = 1.52, 1.42–1.62)!!!

Yes, stopping metformin was associated with all the badness of the heart and kidneys

PS- no association observed for the risk of lactic acidosis (still)

Obviously, these are both observational studies so there could be unaccounted for confounders that can only truly be ruled out with an RCT. Now that metformin is $4 a month at Walmart and the new fancy diabetic drugs are $20-$40 per day it is very unlikely we will see the proper drug company run trial anytime in the near future. However it does seem possible and even reasonable we continue metformin even at smaller doses (500mg daily or 500mg BID) may actually decrease the one thing we are all trying to fight against…..death