, 15 tweets, 11 min read Read on Twitter

For my first #Tweetorial, I will start with a question:

Which of the following medications from the SGLT2 inhibitor class have been shown to decrease cardiovascular morbidity and mortality?

#Diabetes #EndoTwitter #MedEd #MedTwitter #DM2 #T2D #CardioTwitter

Sodium glucose transporters (SGLT) in proximal tubules mediate glucose reabsorption.

Na/K ATPase moves Na out & K into the cell ➡️gradient for Na to flow intracellular

SGLT uses this potential to move glucose against its gradient from the tubular fluid into the cell.

SGLT2 inhibitors block glucose reabsorption
➡️renal glucose excretion
➡️glucose levels⬇️

Because this has nothing to do with insulin, they usually don’t cause hypoglycemia or weight gain.

Actually, because of the osmotic diuresis, they decrease blood pressure & weight.

Remember they arent 1st line therapy for most w/ type 2 DM.

Initial therapy usually starts w/ diet, weight reduction, exercise, & metformin.

Consider adding if:
✅not at goal on metformin + lifestyle
✅cardiovascular disease (see later tweets)
✅obesity or hypertension

Because they cause mild volume depletion, use carefully with NSAIDs, ACE inhibitors, ARBs, diuretics, hypovolemia, heart failure, & liver injury.

Also, because the warm, dark, & sugar-filled urine is a breeding ground, careful in patients w/ UTIs or GU yeast infections.

Following the CV concerns with rosiglitazone, in ‘08 @US_FDA said for new #T2D meds, “sponsors should demonstrate that the therapy will not result in an unacceptable increase in cardiovascular risk.”

There have since been many trials looking at CV safety – see next tweets.

The EMPA-REG from @Boehringer & @LillyPad looked at 7K patients with DM2 and CVD, randomized to EMPAGLIFLOZIN or placebo. No surprise, these patients were also on many other meds for HTN, lipids, & DM (incl. metformin & insulin).

The CANVAS trials (2 of them) from @JannsenUS also looked at high-risk patients with DM2 with established CVD or CVD risk factors. Patients were randomized to CANAGLIFLOZIN or placebo. These patients were similarly taking many other meds for HTN, lipids, & DM.

DECLARE-TIMI trial from @AstraZeneca & @BMSNews also looked at high-risk patients w/ DM2 & with CVD or at risk for CVD. Patients were randomized to DAPAGLIFLOZIN or placebo.

Important to note that fewer patients here had established CVD compared with the other 2 trials.

All of the studies lead to reductions in weight, systolic & diastolic BP (without a change in HR), and uric acid. All lead to an increase in LDL and HDL, as well as in genital infections.

The differences among them are depicted in the table here:

What's fascinating is the minimal A1c reduction, suggesting CV benefit is not from glycemic control.
So why the benefit? Some proposed mechanisms are
⬇️ BP without ⬆️ HR
⬇️ plasma volume
⬇️ arterial stiffness
⬇️ SNS activity
⬆️ ketones (more readily utilizable ATP source)

So, back to original question:

Which of the following #diabetes medications have been shown to decrease cardiovascular morbidity & mortality?

#EndoTwitter #MedTwitter #MedEd #CardioTwitter #DM2 #T2D

While Dapagliflozin has shown improvement in heart failure hospitalization, only Canagliflozin & Empagliflozin have been shown to decrease cardiovascular morbidity and mortality.

In response to this (and to recent data about GLP-1 receptor agonists), the @ADA released new “Standards of Medical Care in Diabetes” earlier this year.

Check out the awesome, updated #diabetes treatment algorithm.
Missing some Tweet in this thread?
You can try to force a refresh.

Like this thread? Get email updates or save it to PDF!

Subscribe to David A. Cohen
Profile picture

Get real-time email alerts when new unrolls are available from this author!

This content may be removed anytime!

Twitter may remove this content at anytime, convert it as a PDF, save and print for later use!

Try unrolling a thread yourself!

how to unroll video

1) Follow Thread Reader App on Twitter so you can easily mention us!

2) Go to a Twitter thread (series of Tweets by the same owner) and mention us with a keyword "unroll" @threadreaderapp unroll

You can practice here first or read more on our help page!

Follow Us on Twitter!

Did Thread Reader help you today?

Support us! We are indie developers!

This site is made by just three indie developers on a laptop doing marketing, support and development! Read more about the story.

Become a Premium Member ($3.00/month or $30.00/year) and get exclusive features!

Become Premium

Too expensive? Make a small donation by buying us coffee ($5) or help with server cost ($10)

Donate via Paypal Become our Patreon

Thank you for your support!