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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?
💥Let’s review the following about

⚡️Mechanism of action
⚡️Safety profile
⚡️Cardiovascular benefits
💥How does Metformin work?

⚡️It inhibits gluconeogenesis in the liver by mitochondrial inhibition & by ⬆️ activation of AMP-kinase👇🏽
⚡️It ⬆️ insulin sensitivity
⚡️It may have additional pleiotropic
💥Merformin is an effective anti-glycemic agent
⚡️⬇️ A1C by 1-1.5%
⚡️Does not cause weight gain
⚡️⬇️ risk of hypoglycemia
⚡️Low cost

Additionally it:
☄️⬇️ incidence of T2DM in high- risk pts.👇🏽
☄️Effective in Rx of Gestational DM & PCOS👇🏽
💥Metformin has been used for 60+ years
⚡️Generally safe
⚡️Risk 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 <30👇🏽
💥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 mortality
☄️39% ⬇️ in MI
💥10-year follow-up study of UKPDS Cohort showed that the Metformin group had micro/macrovascular benefits even in post-trial period👇🏽

But UKPDS Trial has limitations
☄️~80% pts. white
☄️Small: N=342 Met. ,N=411 Diet
☄️Metformin used only in over-wt pts.
💥What do the meta-analyses show regarding the CV benefits of Metformin in T2DM?

⚡️Results are conflicting - some show benefit & some don’t👇🏽
⚡️Meta-analyses have included retrospective/observational studies which impacts the strength of these findings
💥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 conducted
💥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
💥Current trials have used SGLT2 Inhibitors and GLP-1 RA as ‘add-on’ therapy to metformin in T2DM
💥Lack of recent & large trials in diverse pt. populations has caused some uncertainty re: the CV benefits associated w/ metformin use in T2DM

💥But as things stand, Metformin remains the 1st line drug therapy for all T2DM patients

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