Know When to Use a GLP-1 Agonist or SGLT2i First-Line

You’ll hear debate about whether metformin should still be first-line for all patients with type 2 diabetes.

It continues to be the gold standard for most patients based on its established efficacy and safety...and low cost.

Metformin also has possible CV benefits...and can be used in patients with eGFR down to 30 mL/min/1.73 m².

But robust evidence shows that adding a GLP-1 agonist (Ozempic, etc) or SGLT2 inhibitor (Farxiga, etc) to metformin improves cardiorenal outcomes.

And limited data suggest these benefits are independent of metformin...based on subgroups and pooled analyses of CV studies.

That’s why guidelines recommend these newer meds for “compelling indications” in type 2 diabetes...regardless of A1c goal or metformin use.

Still, weigh side effects...and prior auths or high co-pays.

GLP-1 agonists can cause GI effects...carry warnings, such as rare pancreatitis or gallbladder disease...and cost about $1,000/month. Plus most are injectable...and shortages are an ongoing issue.

SGLT2 inhibitors are linked to volume depletion, genital yeast infections, rare Fournier’s gangrene, etc...and cost about $600/month.

Don’t abandon’s still practical and often needed in combo. But tailor first-line meds based on cost, comorbidities, etc.

SGLT2 inhibitors. Consider one of these first-line in a patient with type 2 diabetes and heart failure...chronic kidney disease (CKD)...or CV disease or multiple risks.

Keep in mind, SGLT2 inhibitors can be started down to an eGFR of 20 mL/min/1.73 m² for kidney and CV benefits...and continued until dialysis starts. But glucose lowering is limited at a low eGFR.

GLP-1 agonists. For a patient with type 2 diabetes and CV disease or multiple CV risks, consider starting with a GLP-1 agonist with CV benefit...Ozempic (semaglutide), Trulicity (dulaglutide), or Victoza (liraglutide) reduce risk of CV events.

Or for CKD, think about Ozempic, Trulicity, or Victoza. These may slow CKD progression...but have less data than SGLT2 inhibitors.

Use our resource, Improving Diabetes Outcomes, to fine-tune A1c targets, BP and lipid management, monitoring, and more.

Key References

  • Diabetes Care. 2023 Jan 1;46(Suppl 1):S140-S157
  • Diabetes Care. 2023 Jan 1;46(Suppl 1):S158-S190
  • Diabetes Care. 2022 Nov 1;45(11):2753-2786
  • N Engl J Med. 2023 Jan 12;388(2):117-127
Pharmacist's Letter. February 2023, No. 390207

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