Major Research Findings

Patients with type 2 diabetes mellitus (T2DM) are at high risk for cardiovascular (CV) disease; however, conclusive evidence that glycemic control leads to improved cardiovascular outcomes is lacking. Saxagliptin is a potent, selective dipeptidyl peptidase-4 inhibitor approved as an adjunct to diet and exercise to improve glycemic control in adults with T2DM. Saxagliptin was evaluated in a series of phase III trials as monotherapy; add-on therapy to metformin, a sulfonylurea, or a thiazolidinedione; and as initial therapy in combination with metformin. Saxagliptin consistently improved glycemic control (as reflected by significant decreases in glycated hemoglobin, fasting plasma glucose, and postprandial glucose compared with controls) and was generally well tolerated. In these analyses, saxagliptin had clinically neutral effects on body weight, blood pressure, lipid levels, and other markers of CV risk compared with controls. A retrospective meta-analysis of 8 phase II and phase III trials found no evidence that saxagliptin increases CV risk in patients with T2DM (Cox proportional hazard ratio, 0.43; 95% CI, 0.23-0.80 for major adverse cardiovascular events retrospectively adjudicated). Instead, it raised the hypothesis that saxagliptin may reduce the risk of major adverse CV events. A long-term CV outcome trial, Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus-THrombolysis in Myocardial Infarction 53 (SAVOR-TIMI 53) is currently ongoing to determine whether saxagliptin reduces CV risk in T2DM. 1

Benefits and Risks

Benefits Summary

Saxagliptin has been shown to improve glycemic control in patients with type 2 diabetes and is generally well tolerated. It does not appear to negatively impact cardiovascular risk factors such as weight, blood pressure, and lipid levels. Additionally, there is a hypothesis that saxagliptin might reduce the risk of major adverse cardiovascular events. 1

Risks Summary

Currently, there is no evidence that saxagliptin increases cardiovascular risk in patients with type 2 diabetes. 1

Comparison of Studies

Similarities

These studies consistently demonstrate that saxagliptin improves glycemic control in patients with type 2 diabetes and is generally well tolerated. 1

Differences

The studies involved different uses of saxagliptin, including monotherapy, add-on therapy, and initial therapy. Some studies also evaluated the effect of saxagliptin on cardiovascular risk. 1

Consistency and Contradictions of Results

The results of these studies are consistent, demonstrating that saxagliptin improves glycemic control in patients with type 2 diabetes, is well tolerated, and does not increase cardiovascular risk. However, longer-term studies are necessary to determine if saxagliptin may reduce the risk of cardiovascular events. 1

Considerations for Real-World Application

Saxagliptin can be a helpful addition to diet and exercise for improving glycemic control in adults with type 2 diabetes. However, it is important to note that longer-term studies are needed to fully understand the impact of saxagliptin on cardiovascular events. It's crucial to consult with your doctor to discuss the best treatment options for your individual situation. 1

Limitations of Current Research

The studies included in this review are relatively short-term, not allowing for a complete evaluation of the long-term effects of saxagliptin on cardiovascular events. Additionally, these studies may not have adequately assessed the impact of saxagliptin on specific patient populations, such as individuals with other health conditions like kidney disease or heart failure. 1

Future Directions for Research

Future research should focus on evaluating the long-term impact of saxagliptin on cardiovascular events. Studies should also investigate the effects of saxagliptin on specific patient populations, taking into account the presence of other health conditions. 1

Conclusion

Saxagliptin is a medication that can improve glycemic control in patients with type 2 diabetes and is generally well tolerated. Currently, there is no evidence to suggest that saxagliptin increases cardiovascular risk. However, longer-term studies are needed to determine if saxagliptin may reduce the risk of cardiovascular events. It's important to discuss your individual treatment options with your doctor. 1