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Current American Diabetes Association guidelines recommend Metformin as the 1st line therapy for all T2DM patients
But should Metformin be the 1st line therapy in T2DM patients with cardiovascular disease?1/
#Metformin
#endotwitter
#cardiotwitter
Let’s review the following about Metformin:
Mechanism of actionSafety profileCardiovascular benefits2/
How does Metformin work?It inhibits gluconeogenesis in the liver by mitochondrial inhibition & by 
activation of AMP-kinaseIt insulin sensitivity It may have additional pleiotropic effects
3/
Merformin is an effective anti-glycemic agent 
A1C by 1-1.5%Does not cause weight gain risk of hypoglycemia Low costAdditionally it:
incidence of T2DM in high- risk pts.Effective in Rx of Gestational DM & PCOS4/
Metformin has been used for 60+ years Generally safeRisk of Metformin-associated Lactic Acidosis(MALA) is very low Risk for MALA: in systemic hypoperfusion In CKD: use Metformin w/ caution if GFR b/w 30-45 & don’t use it if GFR <305/
What are the CV benefits associated with Metformin use in T2DM?Strongest data for Metformin use comes from the UKPDS Group
Metformin vs Diet Rx in over- weight T2DM pts.
Metformin group had:
36% all-cause mortality39% in MI6/
10-year follow-up study of UKPDS Cohort showed that the Metformin group had micro/macrovascular benefits even in post-trial periodBut UKPDS Trial has limitations
~80% pts. white Small: N=342 Met. ,N=411 DietMetformin used only in over-wt pts.7/
What do the meta-analyses show regarding the CV benefits of Metformin in T2DM?Results are conflicting - some show benefit & some don’tMeta-analyses have included retrospective/observational studies which impacts the strength of these findings 8/
Would Metformin show CV benefits if the trial were to be conducted today in a large & diverse cohort?Especially given that the drugs/therapies to Rx CV disease have changed considerably since the 1980s/90s when UKPDS Trial was conducted9/
FDA now requires all new anti-diabetic drugs to have proven non-inferiority compared to standard treatment in major CV outcomes before the new drug approval New DM drugs, SGLT2 Inh. & GLP-1 RA, have shown superiority as they CV events/mortality 10/
Current trials have used SGLT2 Inhibitors and GLP-1 RA as ‘add-on’ therapy to metformin in T2DM11/
Lack of recent & large trials in diverse pt. populations has caused some uncertainty re: the CV benefits associated w/ metformin use in T2DMBut as things stand, Metformin remains the 1st line drug therapy for all T2DM patients12/
