Table 2.
Considerations for Selecting Between Glucagon-Like Peptide-1 Receptor Agonist and Sodium-Glucose Cotransporter 2 Inhibitor
| Considerations | GLP-lRAs may be a better choicea | SGLT2 inhibitors may be a better choicea | Rationale |
|---|---|---|---|
| Cardiorenal | Established atherosclerotic cardiovascular and/or cerebrovascular disease; eGFR <30 mL/min/1.73 m2 | HF or CKD predominates | GLP-lRAs primarily reduce atherosclerotic events, including myocardial infarction and stroke. SGLT2 inhibitors have shown benefits in preventing and managing HF. GLP-lRAs (semaglutide, liraglutide, and dulaglutide) can be used in eGFR <30 mL/min/1.73 m2; no SGLT2 inhibitor is currently FDA approved for use in eGFR <30 mL/min/1.73 m2. |
| Glycemic control and DKA | More HbAlc reduction needed; history of DKA | GLP-lRAs are associated with greater HbAlc reduction than SGLT2 inhibitors. SGLT2 inhibitors are associated with a rare risk of DKA. | |
| Comorbidities | Obesity; frequent genital mycotic infections; osteoporosis or history of fractures; lower-limb ulcers or amputations | Active gallbladder disease; pancreatitis; gastroparesis or delayed gastric emptying; personal or family history of MTC or MEN-2; history of proliferative retinopathy | GLP-lRAs are associated with a greater degree of weight loss compared with SGLT2 inhibitors, which are associated with genital mycotic infections (eg, balanitis and vulvovaginal candidiasis). Fournier gangrene has also been reported. CANVAS reported an increased risk of fractures and amputations with canagliflozin, although this was not seen in the CREDENCE trial and has not been seen with other SGLT2 inhibitors. GLP-lRAs are associated with a higher risk of gallbladder disease. Cases of acute and chronic pancreatitis have been reported with GLP-1RA, although this risk has not been borne out in cardiovascular outcome trials or other large studies. GLP-lRAs can slow gastric emptying and can thus exacerbate symptoms in individuals with gastroparesis or delayed gastric emptying. GLP-lRAs have been associated with an increased risk of thyroid C-cell tumors in rodents, and thus a personal or family history of MTC or MEN-2 is a contraindication for GLP-1RA. A small but substantial increase in worsening diabetic retinopathy was observed with injectable semaglutide and has been attributed to rapid lowering of blood glucose. |
| Other | Patient preference | Patient preference | NA |
Abbreviations: CANVAS, Canagliflozin Cardiovascular Assessment Study; CKD, chronic kidney disease; CREDENCE, Canagliflozin and Renal Events in Diabetes and Nephropathy Clinical Evaluation; DKA, diabetic ketoacidosis; eGFR, estimated glomerular filtration rate; FDA, US Food and Drug Administration; GLP-1RA,g lucagon-like peptide-1 receptora gonist; HbA1c, hemoglobin A1c; HF, heart failure; MEN-2, multiple endocrine neoplasia type 2; MTC, medullary thyroid cancer; NA, not applicable; SGLT2, sodium-glucose cotransporter 2.
Many patients are reasonable candidates for either a GLP-1RA or an SGLT2 inhibitor. Concurrent use should be considered among eligible patients in the absence of prohibitive polypharmacy or cost.