From the FDA Drug Label
Saxagliptin 2.5 mg and 5 mg add-on to metformin HCl provided significant improvements in A1C, FPG, and PPG compared with placebo add-on to metformin HCl (Table 5). To qualify for enrollment, patients were required to be on a stable dose of metformin HCl (1,500 to 2,550 mg daily) for at least 8 weeks. Following the lead-in period, eligible patients were randomized to 2.5 mg, 5 mg, or 10 mg of saxagliptin or placebo in addition to their current dose of open-label metformin HCl.
The recommended dosing for Saxagliptin and Metformin is:
- Saxagliptin: 2.5 mg or 5 mg daily
- Metformin: 1,500 to 2,550 mg daily, with patients required to be on a stable dose for at least 8 weeks prior to enrollment 1 Key points:
- Saxagliptin can be added to metformin HCl for patients with inadequate glycemic control
- The dose of saxagliptin can be either 2.5 mg or 5 mg daily
- Metformin HCl should be at a stable dose of 1,500 to 2,550 mg daily for at least 8 weeks prior to adding saxagliptin.
From the Research
Saxagliptin-metformin combination therapy should be dosed once daily with meals, with a typical starting dose of 2.5 mg saxagliptin/500 mg metformin, which can be titrated up based on glycemic control and tolerability, as saxagliptin has been shown to be effective in combination with metformin in reducing HbA1c levels, with a low risk of hypoglycemia and a favorable cardiovascular profile 2, 3.
Key Considerations
- The maximum recommended daily dose is 5 mg saxagliptin/2000 mg metformin, given as 2.5 mg/1000 mg twice daily is not supported by the most recent evidence, instead, saxagliptin can be given once daily 4, 5.
- Patients should take the medication with food to reduce gastrointestinal side effects from metformin.
- Dose adjustments are necessary for patients with renal impairment; saxagliptin-metformin is not recommended when eGFR is below 45 mL/min/1.73m².
- For patients transitioning from separate tablets, match the current total daily doses of each component.
Mechanism of Action
- Saxagliptin inhibits DPP-4 to increase incretin hormones that stimulate insulin secretion, while metformin decreases hepatic glucose production and improves insulin sensitivity.
Side Effects and Monitoring
- Common side effects include headache, diarrhea, and upper respiratory infections.
- Patients should be monitored for hypoglycemia, especially when used with other glucose-lowering medications.
Evidence Summary
- The clinical efficacy of saxagliptin 5 mg/day in combination with metformin has been demonstrated in several randomized, double-blind, placebo-controlled, multicentre, phase III trials, with significant reductions in HbA1c levels and a low risk of hypoglycemia 2, 3.
- Saxagliptin has been shown to be well tolerated, with a favorable cardiovascular profile, and may have additional non-glycemic benefits, such as reducing the risk of major adverse cardiovascular events 3, 6.