From the Guidelines
Saxagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor that works by blocking the enzyme DPP-4, which normally breaks down incretin hormones like glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), as reported in the most recent study 1.
Mechanism of Action
The mechanism of action of saxagliptin involves inhibiting the DPP-4 enzyme, which increases the levels and prolongs the action of incretin hormones in the bloodstream. This enhanced incretin effect leads to several beneficial actions in diabetes management, including:
- Increased insulin secretion from pancreatic beta cells in a glucose-dependent manner
- Decreased glucagon secretion from pancreatic alpha cells, which reduces hepatic glucose production
- Slowed gastric emptying
- Increased satiety
Dosage and Efficacy
Saxagliptin is typically dosed at 2.5-5 mg once daily, with the lower dose recommended for patients with moderate to severe renal impairment, as noted in 1. The medication is effective at lowering HbA1c by approximately 0.5-0.8% and has a favorable side effect profile with minimal risk of hypoglycemia when used as monotherapy.
Safety Profile
Unlike some other antidiabetic medications, saxagliptin does not cause weight gain and may be weight neutral, as reported in 1. However, it is essential to consider the potential increased risk of heart failure hospitalization associated with saxagliptin, as observed in the SAVOR-TIMI 53 trial 1 and subsequent studies 1.
Key Points
- Saxagliptin works by inhibiting the DPP-4 enzyme, increasing incretin hormone levels and activity
- The medication has a favorable side effect profile with minimal risk of hypoglycemia when used as monotherapy
- Saxagliptin is effective at lowering HbA1c and may be weight neutral
- Potential increased risk of heart failure hospitalization should be considered when prescribing saxagliptin.
From the Research
Mechanism of Action of Saxagliptin
- Saxagliptin is a selective, reversible inhibitor of dipeptidyl peptidase-4 (DPP-4) 2, 3, 4, 5, 6
- By inhibiting DPP-4, saxagliptin reduces the degradation of endogenous incretin hormones, resulting in increased glucose-dependent insulin release and decreased glucagon secretion from the pancreas 2, 3, 4, 5, 6
- The incretin hormones affected by saxagliptin include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) 2, 3, 4, 5, 6
- Saxagliptin increases intact plasma GLP-1 and GIP concentrations, augmenting glucose-dependent insulin secretion 2
Pharmacokinetics and Pharmacodynamics
- Saxagliptin is orally absorbed and can be administered with or without food 2
- The half-life of plasma DPP-4 inhibition with saxagliptin 5 mg is ~27 h, which supports a once-daily dosing regimen 2
- Saxagliptin is metabolized by cytochrome P450 (CYP) 3A4/5 and is eliminated by a combination of renal and hepatic clearance 2
- Saxagliptin has a predictable pharmacokinetic and pharmacodynamic profile 2
Clinical Benefits
- Saxagliptin has been shown to improve glycemic control in patients with type 2 diabetes mellitus, as measured by mean glycosylated haemoglobin (HbA(1c)) levels 3, 4, 5, 6
- Saxagliptin has a low risk of hypoglycemia due to its glucose-dependent mechanism of action 3, 4, 5, 6
- Saxagliptin is generally well tolerated, with most adverse events being of mild to moderate severity 3, 4, 5, 6