Saxagliptin overview: special focus on safety and adverse effects

@article{Ali2013SaxagliptinOS,
  title={Saxagliptin overview: special focus on safety and adverse effects},
  author={Shamsa Ali and Vivian A. Fonseca},
  journal={Expert Opinion on Drug Safety},
  year={2013},
  volume={12},
  pages={103 - 109}
}
Introduction: Saxagliptin (see drug summary box) is a glucose-lowering agent that belongs to the class of Dipeptidylpeptidase-4 (DDP-4) inhibitors used in the treatment of T2DM. Clinical efficacy of saxagliptin as single agent as well as in combination with other medications used for the treatment of T2DM has been well established in several randomized trials. Treatment with saxagliptin is effective, generally safe and well tolerated, apart from a small increase in the incidence of infections… 

Saxagliptin for the treatment of diabetes - a focus on safety

The tolerability and safety profile of Saxagliptin, a potent and selective DPP-4 inhibitor that has emerged as a therapeutic option for T2D, is discussed, including cardiovascular, renal, pancreatic, hepatic and bone adverse events.

SAXAGLIPTIN: A SYSTEMATIC REVIEW ON ITS PHARMACOLOGICAL POTENTIAL AND ANALYTICAL ASPECTS

The selective, reversible dipeptidyl peptidase-4 inhibitor Saxagliptin and its active metabolite M2 are used to improve the glycaemic control in type 2 diabetic patients.

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All currently available dipeptidyl peptidase-4 (DPP-4) inhibitors appear to be appropriate pharmacotherapeutic choices in patients with declining renal function, with linagliptin affording the added advantage of not requiring dose adjustment or periodic monitoring of drug-related kidney function, while caution is warranted with the use of glucagon-like peptide-1 (GLP-1) receptor agonists in Patients with moderate or severe renal impairment.

Pharmacokinetics, safety, and efficacy of DPP-4 inhibitors and GLP-1 receptor agonists in patients with type 2 diabetes mellitus and renal or hepatic impairment. A systematic review of the literature

All currently available dipeptidyl peptidase-4 (DPP-4) inhibitors appear to be appropriate pharmacotherapeutic choices in patients with declining renal function, with linagliptin affording the added advantage of not requiring dose adjustment or periodic monitoring of drug-related kidney function, while caution is warranted with the use of glucagon-like peptide-1 (GLP-1) receptor agonists in Patients with moderate or severe renal impairment.

Pharmacokinetics and Clinical Use of Incretin-Based Therapies in Patients with Chronic Kidney Disease and Type 2 Diabetes

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The already large reassuring experience with DPP-4 inhibitors in patients with CKD offers new opportunities to the clinician, whereas more caution is required with GLP-1 receptor agonists because of the limited experience in this population.

References

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This post-hoc analysis in a cohort of US patients with T2DM uncontrolled on monotherapy suggests that saxagliptin 2.5 or 5 mg as add-on therapy to OADs results in improvement across key glycemic parameters compared with placebo add- on and was generally safe and well tolerated.

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This review analyses the pro and contra of using a combination of saxagliptin and metformin (separately or as a fixed-dose combination) in type 2 diabetic patients with moderate or severe RI.

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Clinical trials have demonstrated that treatment with saxagliptin lowers blood glucose levels, with good tolerability and safety, making once-daily treatment feasible, effective and safe.

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In treatment-naïve patients with T2DM, saxagliptin monotherapy demonstrated statistically significant improvement in HbA1c compared with placebo at 24 weeks and was generally well tolerated for up to 76‬weeks.

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Besides their pharmacodynamic properties leading to effective glucose‐lowering effect without inducing hypoglycaemia or weight gain, DPP‐4 inhibitors show favourable PK properties, which contribute to a good efficacy/safety ratio for the management of T2DM in clinical practice.

Influence of Renal or Hepatic Impairment on the Pharmacokinetics of Saxagliptin

One-half the usual dose of saxagliptin 5mg (i.e. 2.5 mg orally once daily) is recommended for patients with moderate (CLCR 30–50 mL/min) or severe renal impairment or ESRD, but no dose adjustments are recommended for those with mild kidney impairment or any degree of hepatic impairment.

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Saxagliptin, when coadministered with simvastatin, diltiazem extended-release, or ketoconazole, was safe and generally well tolerated in healthy subjects and a limitation to the lowest clinical dose of saxagli leptin (2.5 mg) is proposed when it is coadministering with a potent CYP3A4 inhibitor such as ketconazole.

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Metformin is considered to be the first-line drug therapy for the management of Type 2 diabetes. Incretin-based therapies, and especially dipeptidyl peptidase-4 inhibitors, offer new opportunities

Effect of saxagliptin monotherapy in treatment-naïve patients with type 2 diabetes

Once-daily saxagliptin monotherapy for 24 weeks was generally well tolerated and demonstrated clinically meaningful reductions in key parameters of glycemic control vs. placebo.

The Efficacy and Safety of Saxagliptin When Added to Metformin Therapy in Patients With Inadequately Controlled Type 2 Diabetes With Metformin Alone

Saxagliptin once daily added to meetformin therapy was generally well tolerated and led to statistically significant improvements in glycemic indexes versus placebo added to metformin in patients with type 2 diabetes inadequately controlled with met formin alone.