SGLT-2 Inhibitors and GLP-1 Receptor Agonists: Comprehensive List and Clinical Applications
SGLT-2 inhibitors and GLP-1 receptor agonists are two medication classes that significantly reduce cardiovascular and renal events in patients with type 2 diabetes, with benefits extending beyond glycemic control to include mortality reduction and improved quality of life.
SGLT-2 Inhibitors
Available Medications
- Dapagliflozin
- Empagliflozin
- Canagliflozin
- Ertugliflozin
- Sotagliflozin (dual SGLT-1/SGLT-2 inhibitor)
Mechanism of Action
- Inhibit sodium-glucose cotransporter-2 in renal tubules
- Reduce glucose reabsorption from urine
- Lower renal glucose threshold
- Promote urinary glucose excretion 1
Clinical Benefits
- Reduce HbA1c by 0.5-1.0%
- Reduce body weight by 1.5-3.5 kg
- Lower systolic blood pressure by 3-5 mmHg
- Reduce major cardiovascular adverse events
- Decrease hospitalization rates for heart failure
- Slow progression of kidney disease 1, 2
Dosing Considerations
- Empagliflozin: 10-25 mg daily
- Canagliflozin: 100-300 mg daily
- Dapagliflozin: Standard dosing based on indication
- Ertugliflozin: Standard dosing based on indication 1
Renal Dosing
- eGFR ≥45 mL/min/1.73m²: No dose adjustment required
- eGFR <45 mL/min/1.73m²: Generally not recommended for glucose control (though may be used for cardiorenal benefits at lower eGFR) 1, 2
Adverse Effects
- Genitourinary tract infections
- Risk of euglycemic diabetic ketoacidosis
- Volume depletion/hypotension
- Canagliflozin: increased risk of lower limb amputations and bone fractures 2, 3
GLP-1 Receptor Agonists
Available Medications
- Exenatide (short and extended-release)
- Liraglutide
- Lixisenatide
- Beinaglutide
- Semaglutide (oral and injectable)
- Dulaglutide
- Tirzepatide (dual GIP/GLP-1 receptor agonist) 1
Mechanism of Action
- Activate GLP-1 receptors
- Enhance insulin secretion (glucose-dependent)
- Inhibit glucagon secretion
- Delay gastric emptying
- Reduce food intake via central appetite suppression 1
Clinical Benefits
- Effective glucose lowering
- Significant weight reduction
- Reduce major adverse cardiovascular events
- Protective effects in patients with established cardiovascular disease
- Renoprotective benefits 1, 4
Administration
- All require subcutaneous injection except oral semaglutide
- Dosing frequency varies from twice daily to once weekly depending on agent 1
Adverse Effects
- Gastrointestinal symptoms (nausea, vomiting)
- Risk of pancreatitis (rare)
- Caution with history of medullary thyroid cancer
- Semaglutide: caution with proliferative retinopathy 1
Clinical Decision Algorithm for Selection
When to Choose SGLT-2 Inhibitors
- Patient with heart failure (especially with reduced ejection fraction)
- Chronic kidney disease with or without diabetes
- Need for weight loss with minimal hypoglycemia risk
- Established cardiovascular disease requiring additional protection
- Patient preference for oral medication 1, 2, 4
When to Choose GLP-1 Receptor Agonists
- Need for substantial weight loss
- Established atherosclerotic cardiovascular disease
- Need for significant HbA1c reduction without hypoglycemia risk
- Patients with renal insufficiency where SGLT-2 inhibitors may be less effective
- Patient preference for once-weekly dosing (for applicable agents) 1, 4
Combination Therapy Considerations
- Combination of GLP-1 receptor agonists and SGLT-2 inhibitors provides complementary mechanisms
- Cardiovascular and kidney benefits of GLP-1 receptor agonists are consistent regardless of concurrent SGLT-2 inhibitor use 5
- Combined therapy offers additive effects on weight loss and glycemic control
Special Considerations
Cardiovascular Risk Reduction
- Both classes reduce major adverse cardiovascular events by 12-14%
- GLP-1 receptor agonists may provide superior stroke reduction
- SGLT-2 inhibitors provide greater benefit for heart failure hospitalization (3× more effective than GLP-1 receptor agonists) 6
Perioperative Management
- SGLT-2 inhibitors should be discontinued 3-4 days before scheduled surgery to reduce risk of diabetic ketoacidosis 1
Monitoring Recommendations
- When initiating either class in patients on insulin or sulfonylureas:
- Reduce sulfonylurea dose by 50% or basal insulin by 20%
- Monitor blood glucose more closely for 4 weeks
- Educate patients about hypoglycemia symptoms 1
Both medication classes represent significant advances in diabetes management with benefits extending beyond glycemic control to include improvements in cardiovascular and renal outcomes, making them valuable additions to the therapeutic armamentarium for patients with type 2 diabetes.