Onglyza Saxagliptin

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Onglyza - Saxagliptin

• Manufacturer Bristol Myers Squibb
• FDA Approval Date July 31, 2009

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Onglyza - Saxagliptin Clinical Application

• Indication
• Adjunct to diet and exercise for glycemic control
  in type 2 diabetes mellitus
• Place in therapy
• Monotherapy
• Combination therapy with other oral agents
  including metformin, sulfonylureas, and
  thiazolidinediones
• Has not been studied in combination with insulin

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Onglyza - Saxagliptin Clinical Application

• Contraindications
• None
• Warnings
• Children safety and efficacy has not been
  established
• Precaution
• Pregnancy Category B
• Impaired renal function 2.5 mg daily for CrCl
  lt/ 50 ml/min
• May require a lower dose of insulin secretagoges
  (i.e. sulfonylureas) due to increased risk of
  hypoglycemia

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Onglyza - Saxagliptin Drug Facts

• Pharmacology
• Dipeptidyl peptidase 4 (DPP4) inhibitor
• Incretin hormones (i.e. GLP-1, GIP) released from
  small intestine in response to meal ? stimulate
  insulin release from pancreatic beta cells
  ?incretin hormones degraded by DPP4
• T2DM reduced concentration of GLP-1
• Inhibition of DPP4 increases GLP-1 concentrations

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Onglyza - Saxagliptin Drug Facts

• Pharmacokinetics
• A Tmax of 2 hours for saxagliptin and 4 hours
  for its active metabolite (following 5 mg
  once daily dose) 27 increase in
  AUC when given with food
• D negligible protein binding
• M primarily CYP3A4/5 active metabolite is ½ as
  potent
• E t1/2 saxaglitptin 2.5 hrs t1/2 active
  metabolite 3.1 hrs (following 5 mg once
  daily dose). 24, 36, and 75 excreted in
  urine as saxagliptin, active metabolite,
  and total radioactivity, respectively with some
  active renal excretion 22 recovered
  in feces

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Onglyza - Saxagliptin Drug Interactions

• Object Drugs
• Saxagliptin is a substrate of CYP3A4/5 and Pgp
  however, it does not exhibit any induction or
  inhibitory effects

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Onglyza - Saxagliptin Drug Interactions -
Precipitants

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Onglyza - Saxagliptin Adverse Effects

• Common Adverse Effects (5 mg)
• For patients treated with 2.5 mg, headache was
  the only adverse effect that occurred at a rate
  gt5 and more frequently than the placebo

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Onglyza - Saxagliptin Monitoring Parameters

• Efficacy Monitoring
• Plasma glucose (individualized monitoring)
• A1c
• Toxicity Monitoring
• Plasma glucose (hypoglycemia)
• Renal function

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Onglyza - Saxagliptin Prescription Information

• Dosing
• 2.5 5mg po once daily
• 2.5 mg CrCl lt/ 50 ml/min
• Dose reduction may be required in combination
  therapy
• Cost
• 30 tablets 189.98
• 90 tablets 519.95

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Onzyga - Saxagliptin Trial Information

• The Efficacy and Safety of Saxagliptin when Added
  to Metformin Therapy in Patients with
  Inadequately Controlled Type 2 Diabetes with
  Metformin Alone
• DeFronzo RA et al. Diabetes Care 2009
  3216491655
• Design Randomized, double-blind,
  placebo-controlled trial.
• Objective To assess the efficacy of and safety
  of saxagliptin add on therapy in type 2 diabetes
  patients uncontrolled on metformin alone.
• Primary Endpoint Change in A1c from baseline to
  week 24
• Secondary Endpoints Change in FPG from baseline
  to week 24, percentage of pts at A1c lt7, PPG 3-h
  AUC during a 75-g OGTT

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Onzyga - Saxagliptin Trial Information

• Inclusion Criteria
• Men and women with T2DM
• Age 18 77 years
• Inadequate glycemic control (A1C 7.0 10)
• taking a stable dose of metformin (1,500mg 2,
  550 mg/day) for at least 8 weeks before screening
• fasting C-peptide concentration 1.0 ng/ml,
• BMI 40 kg/m2.

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Onzyga - Saxagliptin Trial Information

• Exclusion Criteria
• Symptoms of poorly controlled diabetes
• Hx of DKA or hyperosmolar nonketotic coma
• Use of any other antihyperglycemic medication (8
  weeks before) or insulin (1 year before)
• A cardiovascular event within 6 months before
  study entry
• NYHA stage III/IV CHF and/or known left
  ventricular EF 40
• Chronic or repeated intermittent corticosteroid
  treatment
• Hx of alcohol or drug abuse within the previous
  year
• Tx with potent systemic cytochrome P450 3A4
  inhibitors or inducers
• Active liver disease and/or clinically
  significant abnormalities on screening tests of
  hepatic, renal, endocrine, metabolic, or
  hematologic function, or assessment of an
  immunocompromised state
• Pregnant or breastfeeding

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Onzyga - Saxagliptin Trial Information

• Intervention
• Metformin Saxagliptin 2.5 mg qday
• Metformin Saxagliptin 5 mg qday
• Metformin Saxagliptin 10 mg qday
• Metformin Placebo
• Treatment duration
• 24 weeks

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Onzyga - Saxagliptin Trial Information

• Primary Endpoint Change in A1c from baseline to
  week 24
• P 0.0001

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Onzyga - Saxagliptin Trial Information

• Primary Endpoint Change in A1c from baseline to
  week 24
• P 0.0001 for each combo group

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Onzyga - Saxagliptin Trial Information

• Secondary Endpoint Change in FPG from baseline
  to week 24
• P 0.0001 for each combo group

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Onzyga - Saxagliptin Trial Information

• Secondary Endpoint Percentage of patients
  reaching A1c 7
• P0.0007

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Onzyga - Saxagliptin Trial Information

• Secondary Endpoint PPG 3-h AUC during a 75-g
  OGTT
• P0.0007 for all combo groups

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Onzyga - Saxagliptin Trial Information

• Adverse Effect Analysis

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Onzyga - Saxagliptin Trial Information

• Conclusion
• Saxagliptan is safe and effective at reducing
  A1c, FPG, and PPG versus placebo when added in
  patients with T2DM uncontrolled on metformin.

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Onglyza - Saxagliptin Summary

• Onglyza (Saxagliptin) is a dipeptidyl peptidase
  4 (DPP4) inhibitor indicated (adjunct to diet
  and exercise) as monotherapy or combination
  therapy for glycemic control in type 2 diabetes
  mellitus
• Saxagliptin has not been evaluated in combination
  with insulin exercise caution
• Drug-Drug interactions may occur when
  administered concomitantly with potent CPY3A4
  inducers or inhibitors dose-adjustment may be
  warranted.
• Renal dosing adjustment necessary if CrCl 50
  ml/min

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Onglyza - Saxagliptin References

• http//www.onglyza.com
• Onglyza package insert. Bristol Myers Squibb
  and AstraZeneca Pharmaceuticals. July 2009.
  http//packageinserts.bms.com/pi/pi_onglyza.pdf
• LexiComp Online. http//online.lexi.com/crlsql/ser
  vlet/crlonline
• Facts and Comparisons (eFacts).
  http//online.factsandcomparisons.com.libproxy.lib
  .unc.edu/