Januet xr
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The document discusses Januet XR, a new extended-release formulation combining sitagliptin and metformin for the treatment of type 2 diabetes. Januet XR provides glycemic control through the complementary mechanisms of action of sitagliptin and metformin. Studies showed Januet XR has similar pharmacokinetic properties to immediate-release sitagliptin and provides effective reduction in blood sugar levels with once-daily dosing. Its extended-release formulation aims to improve adherence by reducing dosing frequency compared to the individual components.
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Januet xr
- 1. The New Generation of the DPP-4 Inhibitors: Januet XR ד"ראייזיקוביץאלכס קופתאשדוד מאוחדת חולים
- 2. The History of Treatment for Type 2 Diabetes Adapted from: Kahn et al. lancet, 2014
- 3. Sitagliptin FDA/EMA 2006 Vildagliptin EMA 2010 Linagliptin FDA/EMA 2013 Saxagliptin FDA/EMA 2011 DPP-4 inhibitors for treatment of type 2 diabetes – long term experience
- 5. 5 Effect of DPP-4 inhibitors in monotherapy with comparable baseline Treatment duration: * 18 weeks; † 24 weeks; ‡ 26 weeks. Morning dosing. Source: US prescribing information (linagliptin, saxagliptin, sitagliptin and alogliptin); EU summary of product characteristics (saxagliptin, vildagliptin). Vildagliptin† 50 mg BID 8.6% Saxagliptin†,§ 5 mg OD >=7%-<=10% Linagliptin* 5 mg OD 8.1% Vildagliptin† 50 mg BID 8.4% Sitagliptin* 100 mg OD 8% Sitagliptin† 100 mg OD 8% Saxagliptin† 5 mg OD 8% Linagliptin† 5 mg OD 8.0% -0.6 -0.7 -0.4 -0.6 -0.6 -0.8 -0.5 -0.7 Placebo-corrected, adjusted mean change from baseline HbA1c
- 6. None of the Major Oral Monotherapies Are Able to Address All 3 Core Defects in Type 2 Diabetes Oral Monotherapies Lowers hepatic glucose production SUs Glinides TZDs Improves insulin resistance Improves insulin secretion DPP-4 InhibitorsMetformin MechanismsofAction
- 7. Januet combines two OHAs with complementary mechanisms of action >7 years in market ~60 million prescriptions all over the world FDA and EMA approval www.accessdata.fda.gov/scripts/cder; www.ema.europa.eu/ema/index.jsp
- 8. ProportionsofpatientswithHbA1C <7%atweek104 0 10 20 30 40 50 60 70 Sitagliptin 100 mg qd Metformin 1,000 mg bid Metformin 500 mg bid Sitagliptin 50 mg bid + metformin 1,000 mg bid Sitagliptin 50 mg bid + metformin 500 mg bid 32% 28% 45% 45% 60%
- 10. Januet XR tablet consists of an XR metformin core tablet Metformin XR core is coated with an immediate-release layer of Sitagliptin Sitagliptin layer is coated with a soluble polymeric film MSD data on file
- 11. The extended release formulation allows slow and controlled release of metformin into the GI tract
- 12. Januet (50/500) Januet XR (50/500) 3777 ~= 3666 AUC 0-∞ (nM•hr) 304 ~= 273 Cmax (nM) 3.5 ~= 4 Tmax (hr) MSD data on file Plasma Pharmacokinetic Parameters of Sitagliptin Januet XR group: n=11 healthy adult subjects Januet group: n=12 healthy adult subjects The AUC0-∞ and Cmax for sitagliptin after administration of a single tablet of Januet XR or a single tablet of Januet were similar In the field of pharmacokinetics, the area under the curve (AUC) is the area under the curve (mathematically known as definite integral) in a plot of concentration of drug in blood plasma against time. This is useful when trying to determine whether two formulations of the same dose (for example a capsule and a tablet) release the same dose of drug to the body. Cmax is a term used in pharmacokinetics refers to the maximum (or peak) serum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administrated and prior to the administration of a second dose. Tmax is the term used in pharmacokinetics to describe the time at which the Cmax is observed.
- 13. Januet (50/500) Januet XR (50/500) 9454 ~= 9148 AUC 0-∞ (ng•hr/ml) 1010 < 709 Cmax (ng/ml) 4.0 > 8.0 Tmax (hr) Plasma Pharmacokinetic Parameters of Metformin MSD data on file Januet XR group: n=11 healthy adult subjects Januet group: n=12 healthy adult subjects The mean Cmax value of metformin is 30% lower and the median Tmax value occurs 4 hours later in Januet XR compared with Januet
- 14. Efficacy- Metformin XR Provided Effective reduction in HbA1c Met-XR 1500mg qd Met-XR 2000mg qd Met-XR 1500mg bid Met-IR 1500mg bid Met-XR 1500mg bid Met-IR 1500mg bid Met-XR 2000mg qd Met-XR 1500mg qd 24w endpoint Shwartz et al., Diabetes Care, 2006; Shwartz et al., Expert Opin Drug Metab Toxicol, 2008
- 16. Age Perception and duration of disease Psychological factors Safety Dosing regime: Once daily vs. twice/three times a day Tolerability Polytherapy Cost
- 17. Adapted from Paes et al., Diabetes Carer 1997 98.7 83.1 65.8 0 20 40 60 80 100 1 2 3 Compliance(%) פעםביום פעמיים ביום שלושפעמים ביום Adherence: Once Daily is Better Than Twice Daily
- 18. Age Perception and duration of disease Psychological factors Safety Dosing regime: Once daily vs. twice/three times a day Tolerability Polytherapy Cost
- 19. Frequency of GI AEs During the First Year of treatment within the SAME population Blonde et al., Curr Med Res Opin, 2004
- 20. Age Perception and duration of disease Psychological factors Safety Dosing regime: Once daily vs. twice/three times a day Tolerability Polytherapy Cost
- 21. TECOS
- 22. N= 129 patients with T2DM and ESRD who were on dialysis therapy Arjona Ferreira et al., Am J Kidney Dis. , 2013
- 23. Met DPP4i SGLT2i GLP1RA TZD AGI SU/ GLN Insulin Hypo Neutral Neutral Neutral Neutral Neutral Neutral Moderate- severe/ mild Moderate- severe Weight Slight loss Neutral Loss Loss Gain Neutral Gain Gain Renal/ GU Contraindicated stage 3B, 4,5 Dose adjustme nt maybe required Infections Exenatide BID contraindicate d CrCl<30 May worsen fluid retention Neutral More hypo risk More hypo risk & fluid retention GI AE Moderate Neutral Neutral Moderate Neutral Moderate Neutral Neutral CHF Neutral Neutral Neutral Neutral Moderate Neutral Neutral Neutral CVD Benefit Neutral Increased LDL Neutral Neutral Neutral Neutral Bone Neutral Neutral Neutral Neutral Moderate bone mass loss Neutral Neutral Neutral Profiles of antidiabetic agents Few AE or possible benefits Use with precaution Likelihood of adverse events Adapted from Garber et al. AACe comprehensive diabetes management algorithm 2013. +/- n e u t r a l
- 24. The primary goal: To Achieve Glycemic Control Improved Toleability Improved Pill Burden Improved HbA1C
- 26. SitagliptinMetformin XR Once-daily Fixed-Dose-Combination will provide better glycemic control Powerful efficacy Superior inhibition • Better tolerability • Lower dosing regime -> Possibly Increase Adherence
- 27. Januet XR Dosages מינוןיומירצוי (/סיטגליפטין )מטפורמין הטבליותאותןישליטול תדירות מספרטבליות באריזה 100 /ג"מ 2000 ג"מ 2 טבליות יחד פעםביום 60 100 /ג"מ 1000 ג"מ טבליהאחת פעםביום 30 50"מ ג"מ0001/ג50"מ ג"מ0001/ג 100"מ ג"מ0001/ג /סיטגליפטין מטפורמיןXR:50"מ ג"מ0001/ג50"מ ג"מ005/ג 100"מ ג"מ0001/ג
- 28. The New Generation of the DPP-4 Inhibitors: Januet XR
Editor's Notes
- The proportion of patients that achieved the HbA1C<7 goal was largest in the group that received fixed dose combination therapy The proportions of patients with an HbA1c <7% at week 104 were 60, 45, 45, 28 and 32% for the higher dose coadministration, lower dose co-administration, higher dose metformin, lower dose metformin and sitagliptin groups, respectively.
- JANUET XR is a fixed-dose combination (FDC) product that contains sitagliptin, a dipeptidyl peptidase 4 (DPP-4) inhibitor, in combination with an extended release formulation of the biguanide metformin (metformin XR), which provides for convenient once-daily dosing. Approval of JANUET XR is based on bioequivalence studies and clinical studies evaluating the efficacy and safety of combination therapy with sitagliptin and metformin as separate tablets.
- Tablet Design: JANUET XR tablets consist of an extended-release metformin core tablet coated with an immediate-release layer of sitagliptin and are formulated to gradually release metformin to the upper gastrointestinal (GI) tract . The sitagliptin layer is coated with a soluble polymeric film.
- The tablet absorb water from the stomach. This process results with a slow and controlled release of metformin into the GI tract, while the tablet stays in the stomach. A slow and controlled release results with absorption of most of the metformin into the bloodstream.
- Comparisons for the Plasma Pharmacokinetic Parameters of Sitagliptin after Administration of a Single Januet XR 50 mg/500 mg or administration of a Single Januet 50 mg/500 mg Tablet in Healthy Adult Subjects. The AUC0-∞ and Cmax for sitagliptin after administration of a single Januet XR 50 mg/500 mg tablet and administration of a single Januet 50 mg/500 mg tablet are similar.
- Comparisons for the Plasma Pharmacokinetic Parameters of Metformin after administration of a Single Januet XR 50 mg/500 mg Tablet or Administration of a Januet 50 mg/500 mg Tablet in Healthy Adult Subjects. The AUC0-∞ for metformin after administration of a single Januet XR 50 mg/500 mg tablet and administration of a single Januet 50 mg/500 mg tablet are similar. After administration of a single Januet XR 50 mg/500 mg tablet, the mean Cmax value for metformin is 30% lower and the median Tmax value occurs 4 hours later compared with corresponding values after administration of a single Januet 50 mg/500 mg tablet, which is consistent with the expected modified-release characteristics for metformin associated with the Januet XR formulation.
- Significant (P <0.001) reductions in mean A1C concentrations were observed by week 12 in all treatment groups. A1C levels continued to decline until week 20 and were maintained for the duration of the study (left). The mean changes in A1C concentrations from baseline to end point in all extended-release metformin groups were noninferior to those in the immediate-release metformin group. The reduction in HbA 1c in the Metformin XR 2000 mg q.d. group was greater than for the other groups, indicating greater efficacy at higher doses, which may be related to the linearity of the dose proportionality data for Metformin XR.
- Adherence is influenced by many factors. Here we will show how Januet XR can improve adherence in two forms: Improved dosing regime Improved tolerability
- היעילות בהורדת A1C צפויה להיות זהה, אך מכיוון שההיענות לטיפול גבוהה יותר, זה עשוי להוביל לאיזון גליקמי טוב יותר, וליותר חולים שיגיעו למטרה. היענות החולה לטיפול יורדת ככל שמספר הנטילות של התרופה עולה. במחקר שבוצע בחולי סוכרת בהולנד (כ-90 חולים) נצפתה היענות של כ-2/3 בלבד במטופלים תחת משטר נטילה של 3 פעמים ביום- כלומר כשליש מהכדורים לא נצרכו. בקרב מטופלים תחת משטר נטילה של פעם ביום ההיענות היתה כמעט מלאה.
- Frequency of gastrointestinal adverse events reported in ≥ 1% of 205 patients taking immediate-release metformin (metformin-IR) before switching to metformin-XR. For this analysis, only those symptoms reported in the first year of therapy with immediate-release metformin were compared to the symptoms reported during the year following a switch to metformin-XR. There was a statistically significant reduction in GI AE in patients switched to metformin XR.
- ג'אנואט XR זמין במספר מינונים משולבים: טבליה המשלבת 50 מ"ג סיטהגליפטין עם 1000 מ"ג מטפורמין בשחרור מושהה. טבליה המשלבת 50 מ"ג סיטהגליפטין עם 500 מ"ג מטפורמין בשחרור מושהה. טבליה המשלבת 1000 מ"ג סיטהגליפטין עם 1000 מ"ג מטפורמין בשחרור מושהה. חולים המקבלים 2000 מ"ג מטפורמין ליום יוכלו לקחת 2 טבליות של 50/1000, ביחד, פעם ביום חולים המקבלים 1500 מ"ג מטפורמין ליום יוכלו לקחת טבליה אחת של 50/1000 וטבליה אחת של 50/500, ביחד, פעם ביום חולים המקבלים 1000 מ"ג מטפורמין ליום יוכלו לקחת טבליה אחת של 100/1000, פעם ביום יש לקחת 2 טבליות בבת אחת במינונים הגבוהים, מפאת גודל הכדור. שימו לב יש 60 טבליות באריזה או 30 (במינון הנמוך ). ליעילות מירבית , יש לקחת ג'נואט XR עם האוכל (כלומר לא בצום, לא בבוקר).