Know When a GLP-1 Agonist or SGLT2i May Be Used First-Line

You may see more patients with type 2 diabetes taking a home med other than metformin first-line.

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

It 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 (semaglutide, etc) or SGLT2 inhibitor (dapagliflozin, 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. You may see one of these used first-line in a patient with type 2 diabetes and heart failure...chronic kidney disease (CKD)...or CV disease or multiple CV 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. You may see a GLP-1 agonist used first-line in a patient with type 2 diabetes and CV disease or multiple CV risks.

Ensure it’s a GLP-1 agonist with CV benefit...dulaglutide (Trulicity), liraglutide (Victoza), or semaglutide (Ozempic).

Be aware that dulaglutide, liraglutide, or semaglutide may slow CKD progression...but have less data than SGLT2 inhibitors.

Use our resource, Improving Diabetes Outcomes, for more on 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
  • Diabetes Care. 2022 Dec 1;45(12):3075-3090
  • Medication pricing by Elsevier, accessed Jan 2023
Hospital Pharmacist's Letter. February 2023, No. 390207

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