Adding Dapagliflozin to Metformin in Type 2 Diabetes
Start dapagliflozin 10 mg once daily immediately, taken in the morning with or without food, while continuing metformin 850 mg twice daily. 1
Rationale for This Approach
Your patient's A1C of 7.2% exceeds the recommended target of <7.0% for most adults with type 2 diabetes, indicating the need for treatment intensification. 2 The current metformin dose of 850 mg twice daily (1700 mg total) is below the optimal therapeutic range of 2000 mg daily, but adding dapagliflozin is the appropriate next step rather than simply increasing metformin. 2, 3
Dapagliflozin provides complementary glucose-lowering through a unique insulin-independent mechanism—blocking renal glucose reabsorption—that works synergistically with metformin's reduction of hepatic glucose production. 4, 5 This combination addresses multiple pathophysiologic defects in type 2 diabetes simultaneously.
Expected Glycemic Benefit
Adding dapagliflozin 10 mg to metformin will reduce A1C by an additional 0.5–0.8%, bringing your patient's A1C from 7.2% to approximately 6.4–6.7%, well within the target range. 2, 5
Fasting plasma glucose will decrease by approximately 1.1–1.5 mmol/L (20–27 mg/dL) within the first few weeks. 5, 6
This glucose-lowering effect is sustained for at least 102 weeks based on long-term extension studies. 5
Additional Cardiovascular and Renal Benefits
Dapagliflozin provides cardiovascular and renal protection that is independent of its glucose-lowering effect, making it valuable even beyond glycemic control. 2, 1 The FDA-approved indications include reducing the risk of cardiovascular death, heart failure hospitalization, and progression of chronic kidney disease. 1
For patients with type 2 diabetes and cardiovascular risk factors, the American College of Cardiology gives a Class I recommendation for SGLT2 inhibitors like dapagliflozin. 7, 2
Weight and Blood Pressure Effects
Expect modest weight loss of 2–5 kg over 24–52 weeks, contrasting with the weight gain associated with sulfonylureas or insulin. 5, 8, 9
Systolic blood pressure typically decreases by 2–5 mmHg due to osmotic diuresis and natriuresis. 4, 9
Dosing Specifics
The recommended starting and maintenance dose is 10 mg once daily for cardiovascular and renal protection. 1 While a 5 mg dose exists for glycemic control initiation, the 10 mg dose provides superior A1C reduction (−0.89% vs −0.77% with 5 mg) and is the FDA-approved dose for cardiorenal indications. 1, 6
Take dapagliflozin in the morning with or without food. 1
No dose titration is required—start at the target dose of 10 mg. 1
Continue metformin 850 mg twice daily without interruption. 2, 5
Renal Function Considerations
Before initiating dapagliflozin, verify that your patient's eGFR is ≥25 mL/min/1.73 m². 1 For glycemic control specifically, the FDA recommends initiation only when eGFR ≥45 mL/min/1.73 m², though dapagliflozin can be started at eGFR ≥25 for cardiorenal protection. 1
If eGFR is 45–59 mL/min/1.73 m², continue metformin at the current dose but monitor renal function every 3–6 months. 3, 10
If eGFR is 30–44 mL/min/1.73 m², reduce metformin to 1000 mg daily total (500 mg twice daily). 3, 10
If eGFR falls below 30 mL/min/1.73 m², discontinue metformin but continue dapagliflozin for cardiorenal protection. 10, 1
Volume Status Assessment
Before starting dapagliflozin, assess and correct any volume depletion, particularly in elderly patients or those on diuretics. 7, 1 Dapagliflozin causes osmotic diuresis, which can lead to intravascular volume contraction in vulnerable patients. 7
Counsel your patient about symptoms of volume depletion (dizziness, lightheadedness) and advise adequate fluid intake, especially during the first week of therapy. 10
Safety Profile and Common Adverse Effects
Genital mycotic infections occur in 12–15% of patients on dapagliflozin versus 5% on placebo, but these respond to standard antifungal treatment and rarely require drug discontinuation. 5, 8, 9 Women are at higher risk than men. 4
Urinary tract infections occur in 8–13% of dapagliflozin patients versus 8% on placebo—the increase is modest. 5, 8
Hypoglycemia risk is minimal when dapagliflozin is combined with metformin alone (3.5% vs 40.8% with sulfonylureas). 8
Euglycemic diabetic ketoacidosis is a rare but serious risk; instruct patients to stop dapagliflozin and seek urgent care if they develop nausea, vomiting, abdominal pain, or dyspnea, especially during intercurrent illness. 7, 1
Monitoring Plan
Reassess A1C at 3 months after initiating dapagliflozin to confirm achievement of the <7% target. 2
Check renal function (eGFR) at 3 months, then every 3–6 months if eGFR <60 mL/min/1.73 m². 3, 10
Monitor for signs of genital or urinary infections, particularly in the first 3 months. 5, 9
Assess volume status and blood pressure at follow-up visits. 10, 1
Metformin Optimization Consideration
While your patient is on metformin 850 mg twice daily (1700 mg total), the optimal therapeutic dose is 2000 mg daily (1000 mg twice daily). 2, 3 However, adding dapagliflozin now is more appropriate than simply increasing metformin, because:
The patient's A1C is already above target, requiring dual therapy for adequate control. 2
Dapagliflozin provides complementary mechanisms plus cardiorenal protection that metformin alone cannot deliver. 2, 1
If A1C remains >7% after 3 months on metformin 1700 mg + dapagliflozin 10 mg, then increase metformin to 2000 mg daily. 2, 3
Critical Pitfalls to Avoid
Do not discontinue metformin when adding dapagliflozin—metformin remains the foundational therapy and provides cardiovascular mortality benefit. 2, 5
Do not delay dapagliflozin initiation waiting for metformin optimization alone—at A1C 7.2%, dual therapy is indicated to achieve target within 3 months. 2
Do not withhold dapagliflozin in patients with mild renal impairment (eGFR 45–59)—it remains safe and effective, though glucose-lowering efficacy diminishes as eGFR declines. 10, 1
Do not combine dapagliflozin with DPP-4 inhibitors initially—if further intensification is needed after 3 months, add a GLP-1 receptor agonist instead for superior A1C reduction and cardiovascular benefit. 2