No, Trulicity is NOT an SGLT2 Inhibitor
Trulicity (dulaglutide) is a GLP-1 receptor agonist, not an SGLT2 inhibitor—these are two completely different drug classes with distinct mechanisms of action. 1
Drug Classification
Trulicity (dulaglutide):
- Class: Glucagon-like peptide-1 (GLP-1) receptor agonist 2, 3
- Mechanism: Binds to GLP-1 receptors to enhance glucose-dependent insulin secretion, suppress glucagon, slow gastric emptying, and reduce appetite 1, 4
- Administration: Subcutaneous injection once weekly 2, 5
- Primary effects: Improves glycemic control through insulin-dependent pathways, promotes weight loss (1.5–3.5 kg), and reduces major adverse cardiovascular events by 12–26% 6, 5
SGLT2 Inhibitors (e.g., dapagliflozin, empagliflozin, canagliflozin):
- Class: Sodium-glucose cotransporter-2 inhibitors 7
- Mechanism: Block renal glucose reabsorption in the proximal tubule, causing glucosuria (glucose excretion in urine) through an insulin-independent pathway 7
- Primary effects: Lower blood glucose by eliminating glucose through urine, reduce heart failure hospitalizations, and slow chronic kidney disease progression 7
Key Mechanistic Differences
| Feature | Trulicity (GLP-1 RA) | SGLT2 Inhibitors |
|---|---|---|
| Site of action | Pancreatic β-cells, brain, GI tract [1,4] | Kidney proximal tubule [7] |
| Insulin dependence | Glucose-dependent insulin secretion [6] | Insulin-independent [7] |
| Weight effect | Moderate loss (2–4 kg) [6] | Modest loss via calorie loss in urine [7] |
| CV benefit mechanism | Anti-inflammatory, improved lipid profiles [6] | Hemodynamic effects, reduced preload [7] |
| Renal function impact | Efficacy retained even at eGFR <30 [6] | Glucose-lowering lost below eGFR 45, but cardiorenal benefits persist [7] |
Clinical Implications
When to use Trulicity (GLP-1 RA):
- Type 2 diabetes with established cardiovascular disease or high CV risk (proven MACE reduction of 12% with dulaglutide) 5
- Obesity (BMI >35 kg/m²) requiring significant weight loss 6
- Chronic kidney disease with eGFR 20–60 mL/min/1.73 m² when additional glucose-lowering is needed 6
- Patients requiring cardiovascular protection alongside glycemic control 1
When to use SGLT2 inhibitors:
- Heart failure (with reduced or preserved ejection fraction) to reduce hospitalizations 7
- Chronic kidney disease (eGFR 20–60 mL/min/1.73 m²) to slow progression 7
- Type 2 diabetes when cardiorenal protection is the priority, even if glucose-lowering is minimal 7
Combination therapy:
- GLP-1 receptor agonists and SGLT2 inhibitors can be used together for complementary benefits—GLP-1 RAs provide superior MACE reduction, while SGLT2 inhibitors excel at heart failure and CKD protection 6
Common Pitfall to Avoid
Do not confuse the two classes simply because both are injectable or used in diabetes. Trulicity works through the incretin system (enhancing insulin, suppressing glucagon), while SGLT2 inhibitors work through the kidneys (blocking glucose reabsorption). 1, 7 They are often used together precisely because their mechanisms are complementary, not redundant. 6