From the Research
For a type 2 diabetic with an A1C of 11%, the best three-drug non-insulin regimen would be metformin 1000 mg twice daily, an SGLT-2 inhibitor such as empagliflozin 10-25 mg daily, and a GLP-1 receptor agonist like semaglutide 0.25 mg weekly (titrated up to 1 mg weekly over time). This combination is supported by the most recent and highest quality study available, which compared the effectiveness of empagliflozin and dapagliflozin in patients with type 2 diabetes inadequately controlled with metformin, glimepiride, and dipeptidyl peptide 4 inhibitors 1. The study found that empagliflozin was more effective in reducing HbA1c and improving other cardiometabolic parameters than dapagliflozin.
Key Components of the Regimen
- Metformin reduces hepatic glucose production and improves insulin sensitivity as the foundation of therapy
- The SGLT-2 inhibitor works independently of insulin by increasing glucose excretion through the kidneys, offering cardiovascular and renal benefits
- The GLP-1 agonist stimulates insulin secretion, suppresses glucagon, delays gastric emptying, and reduces appetite, providing powerful A1C reduction
Implementation and Monitoring
Start with metformin and gradually add the other medications over 4-8 weeks to minimize side effects. Regular blood glucose monitoring is essential during this intensive treatment phase, and the patient should be reassessed after 3 months to determine if the regimen is effective or if insulin therapy should be considered. The potential benefits of this combination, including improved glycemic control and reduced risk of cardiovascular events, must be weighed against the potential risks, such as increased risk of genital mycotic infections and urinary tract infections associated with SGLT-2 inhibitors 2, 3.
Rationale for Choice
The choice of empagliflozin over other SGLT-2 inhibitors is based on its demonstrated efficacy and safety in clinical trials, including the study by 1. The addition of a GLP-1 receptor agonist, such as semaglutide, provides a powerful A1C reduction and has been shown to be effective in combination with SGLT-2 inhibitors and metformin. This combination targets multiple pathophysiological defects of diabetes and can potentially lower A1C by 2-3.5%.