As an adjunct to diet and exercise for appropriate patients with type 2 diabetes

JANUVIA: Similar A1C lowering and goal achievement with significantly lower incidence of hypoglycemia and no weight gain, compared with glimepiride + metformin1,2

A1C Goal Achievement for JANUVIA® (sitagliptin) Compared With Glipizide + Metformin A1C Goal Achievement for JANUVIA® (sitagliptin) Compared With Glipizide + Metformin

aLeast squares (LS) mean between-group difference: 0.07% (95% confidence interval [CI], –0.03, 0.16); bJANUVIA + metformin was noninferior to glimepiride + metformin at week 30. Noninferiority was based on the criterion of having an upper bound of the 95% CI less than the prespecified noninferiority bound of 0.4%.

PP = per-protocol.

This is an electronic version of a figure published in Diabetes, Obesity and Metabolism. Volume 13, Issue 2, pages 160–168, February 2011. Lead author: Arechavaleta. Published by Wiley.

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Primary end point: A1C LS mean change from baseline at week 30 for both sitagliptin + metformin was –0.47% (n=443; mean baseline 7.5%) vs –0.54% for glimepiride + metformin (n=436; mean baseline 7.5%); PP population

  • In the full-analysis-set population, patients treated with JANUVIA 100 mg once daily + metformin ≥1500 mg/day (n=509) achieved LS mean A1C reductions from baseline comparable to glimepiride 1–6 mg/day + metformin ≥1500 mg/day (n=509): JANUVIA –0.5% (mean baseline A1C 7.5%); glimepiride –0.5% (mean baseline A1C 7.5%). The mean dose of glimepiride in the all-patients-randomized population was 2.0 mg/day
  • In the PP analysis, from a mean baseline A1C of 7.5%, similar LS mean A1C reductions were seen: JANUVIA 100 mg once daily –0.47% (n=443); glimepiride 1 to 6 mg/day (2.1 mg mean dose) –0.54% (n=436), when added to metformin ≥1500 mg/day
    Note: The PP population included patients without major protocol violations who had observations at baseline and week 30
  • A conclusion in favor of the noninferiority of JANUVIA to glimepiride may be limited to patients with baseline A1C comparable to those included in the study (>70% of patients had baseline A1C <8%)

Established tolerability profile: Significantly lower incidence of hypoglycemia and no weight gain compared with glimepiride + metformin

Tolerability Profile for JANUVIA® (sitagliptin) Compared With Glimepiride + Metformin Tolerability Profile for JANUVIA® (sitagliptin) Compared With Glimepiride + Metformin

cPercentage for patients (APaT population) reporting 1 or more episodes of hypoglycemia; dP<0.001 for between-group difference; eLS mean (± SE) change from baseline in the APaT population; fn values at 30 weeks: 461 for glimepiride + metformin and 465 for JANUVIA + metformin; gFor between-treatment-group comparison at 30 weeks.

APaT = all-patients-as-treated; SE = standard error; LS = least squares.

This is an electronic version of a figure published in Diabetes, Obesity and Metabolism. Volume 13, Issue 2, pages 160–168, February 2011. Lead Author: Arechavaleta. Published by Wiley.

View Study Design 2 >

When added to a sulfonylurea (glimepiride) or insulin, patients treated with sitagliptin experienced increased incidence of hypoglycemia and a mean increase in body weight

  • Hypoglycemia: 12.2% for patients treated with sitagliptin + glimepiride ± metformin vs 1.8% for placebo + glimepiride ± metformin; 15.5% for patients treated with sitagliptin + insulin ± metformin vs 7.8% for placebo + insulin ± metformin. A lower dose of sulfonylurea or insulin may be required to reduce the risk of hypoglycemia
  • Weight gain: +1.8 lb for patients treated with JANUVIA + glimepiride ± metformin vs –0.9 lb for placebo + glimepiride ± metformin; +0.2 lb for patients treated with JANUVIA + insulin ± metformin vs +0.2 lb for placebo + insulin ± metformin

References: 1. Arechavaleta R, Seck T, Chen Y, et al. Efficacy and safety of treatment with sitagliptin or glimepiride in patients with type 2 diabetes inadequately controlled on metformin monotherapy: a randomized, double-blind, non-inferiority trial. Diabetes Obes Metab. 2011;13(2):160–168. 2. Data available on request from Merck Professional Services-DAP, WP1-27, PO Box 4, West Point, PA 19486-0004. Please specify information package DIAB-1086695-0003.

 
Selected Important Risk Information About JANUVIA® (sitagliptin) tablets

JANUVIA is contraindicated in patients with a history of a serious hypersensitivity reaction to sitagliptin, such as anaphylaxis or angioedema.

There have been postmarketing reports of acute pancreatitis, including fatal and nonfatal hemorrhagic or necrotizing pancreatitis, in patients taking JANUVIA. After initiating JANUVIA, observe patients carefully for signs and symptoms of pancreatitis. If pancreatitis is suspected, promptly discontinue JANUVIA and initiate appropriate management. It is unknown whether patients with a history of pancreatitis are at increased risk of developing pancreatitis while taking JANUVIA.

Assessment of renal function is recommended prior to initiating JANUVIA and periodically thereafter. A dosage adjustment is recommended in patients with moderate or severe renal insufficiency and in patients with end-stage renal disease requiring hemodialysis or peritoneal dialysis. Caution should be used to ensure that the correct dose of JANUVIA is prescribed.

There have been postmarketing reports of worsening renal function, including acute renal failure, sometimes requiring dialysis. A subset of these reports involved patients with renal insufficiency, some of whom were prescribed inappropriate doses of sitagliptin.

When JANUVIA was used in combination with a sulfonylurea or insulin, medications known to cause hypoglycemia, the incidence of hypoglycemia was increased over that of placebo. Therefore, a lower dose of sulfonylurea or insulin may be required to reduce the risk of hypoglycemia.

The incidence (and rate) of hypoglycemia based on all reports of symptomatic hypoglycemia were: 12.2% (0.59 episodes/patient-year) for JANUVIA 100 mg in combination with glimepiride (with or without metformin), 1.8% (0.24 episodes/patient-year) for placebo in combination with glimepiride (with or without metformin), 15.5% (1.06 episodes/patient-year) for JANUVIA 100 mg in combination with insulin (with or without metformin), and 7.8% (0.51 episodes/patient-year) for placebo in combination with insulin (with or without metformin).

There have been postmarketing reports of serious hypersensitivity reactions in patients treated with JANUVIA, such as anaphylaxis, angioedema, and exfoliative skin conditions including Stevens-Johnson syndrome. Onset of these reactions occurred within the first 3 months after initiation of treatment with JANUVIA, with some reports occurring after the first dose. If a hypersensitivity reaction is suspected, discontinue JANUVIA, assess for other potential causes for the event, and institute alternative treatment for diabetes.

Angioedema has also been reported with other dipeptidyl peptidase-4 (DPP-4) inhibitors. Use caution in a patient with a history of angioedema with another DPP-4 inhibitor because it is unknown whether such patients will be predisposed to angioedema with JANUVIA.

There have been postmarketing reports of severe and disabling arthralgia in patients taking DPP-4 inhibitors. The time to onset of symptoms following initiation of drug therapy varied from 1 day to years. Patients experienced relief of symptoms upon discontinuation of the medication. A subset of patients experienced a recurrence of symptoms when restarting the same drug or a different DPP-4 inhibitor. Consider DPP-4 inhibitors as a possible cause for severe joint pain and discontinue drug if appropriate.

Postmarketing cases of bullous pemphigoid requiring hospitalization have been reported with DPP-4 inhibitor use. In reported cases, patients typically recovered with topical or systemic immunosuppressive treatment and discontinuation of the DPP-4 inhibitor. Tell patients to report development of blisters or erosions while receiving JANUVIA. If bullous pemphigoid is suspected, JANUVIA should be discontinued and referral to a dermatologist should be considered for diagnosis and appropriate treatment.

There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with JANUVIA or with any other antidiabetic drug.

In clinical studies, the adverse reactions reported, regardless of investigator assessment of causality, in ≥5% of patients treated with JANUVIA as monotherapy and in combination therapy and more commonly than in patients treated with placebo, were upper respiratory tract infection, nasopharyngitis, and headache.

Before prescribing JANUVIA® (sitagliptin) tablets, please read the accompanying Prescribing Information. The Medication Guide also is available.

DIAB-1080639-0011 12/14

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Important Information

JANUVIA is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

JANUVIA should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis.

JANUVIA has not been studied in patients with a history of pancreatitis. It is unknown whether patients with a history of pancreatitis are at increased risk of developing pancreatitis while taking JANUVIA.

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Selected Important Risk Information About JANUVIA® (sitagliptin) tablets

JANUVIA is contraindicated in patients with a history of a serious hypersensitivity reaction to sitagliptin, such as anaphylaxis or angioedema.

There have been postmarketing reports of acute pancreatitis, including fatal and nonfatal hemorrhagic or necrotizing pancreatitis, in patients taking JANUVIA. After initiating JANUVIA, observe patients carefully for signs and symptoms of pancreatitis. If pancreatitis is suspected, promptly discontinue JANUVIA and initiate appropriate management. It is unknown whether patients with a history of pancreatitis are at increased risk of developing pancreatitis while taking JANUVIA.

Assessment of renal function is recommended prior to initiating JANUVIA and periodically thereafter. A dosage adjustment is recommended in patients with moderate or severe renal insufficiency and in patients with end-stage renal disease requiring hemodialysis or peritoneal dialysis. Caution should be used to ensure that the correct dose of JANUVIA is prescribed.

There have been postmarketing reports of worsening renal function, including acute renal failure, sometimes requiring dialysis. A subset of these reports involved patients with renal insufficiency, some of whom were prescribed inappropriate doses of sitagliptin.

When JANUVIA was used in combination with a sulfonylurea or insulin, medications known to cause hypoglycemia, the incidence of hypoglycemia was increased over that of placebo. Therefore, a lower dose of sulfonylurea or insulin may be required to reduce the risk of hypoglycemia.

The incidence (and rate) of hypoglycemia based on all reports of symptomatic hypoglycemia were: 12.2% (0.59 episodes/patient-year) for JANUVIA 100 mg in combination with glimepiride (with or without metformin), 1.8% (0.24 episodes/patient-year) for placebo in combination with glimepiride (with or without metformin), 15.5% (1.06 episodes/patient-year) for JANUVIA 100 mg in combination with insulin (with or without metformin), and 7.8% (0.51 episodes/patient-year) for placebo in combination with insulin (with or without metformin).

There have been postmarketing reports of serious hypersensitivity reactions in patients treated with JANUVIA, such as anaphylaxis, angioedema, and exfoliative skin conditions including Stevens-Johnson syndrome. Onset of these reactions occurred within the first 3 months after initiation of treatment with JANUVIA, with some reports occurring after the first dose. If a hypersensitivity reaction is suspected, discontinue JANUVIA, assess for other potential causes for the event, and institute alternative treatment for diabetes.

Angioedema has also been reported with other dipeptidyl peptidase-4 (DPP-4) inhibitors. Use caution in a patient with a history of angioedema with another DPP-4 inhibitor because it is unknown whether such patients will be predisposed to angioedema with JANUVIA.

There have been postmarketing reports of severe and disabling arthralgia in patients taking DPP-4 inhibitors. The time to onset of symptoms following initiation of drug therapy varied from 1 day to years. Patients experienced relief of symptoms upon discontinuation of the medication. A subset of patients experienced a recurrence of symptoms when restarting the same drug or a different DPP-4 inhibitor. Consider DPP-4 inhibitors as a possible cause for severe joint pain and discontinue drug if appropriate.

Postmarketing cases of bullous pemphigoid requiring hospitalization have been reported with DPP-4 inhibitor use. In reported cases, patients typically recovered with topical or systemic immunosuppressive treatment and discontinuation of the DPP-4 inhibitor. Tell patients to report development of blisters or erosions while receiving JANUVIA. If bullous pemphigoid is suspected, JANUVIA should be discontinued and referral to a dermatologist should be considered for diagnosis and appropriate treatment.

There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with JANUVIA or with any other antidiabetic drug.

In clinical studies, the adverse reactions reported, regardless of investigator assessment of causality, in ≥5% of patients treated with JANUVIA as monotherapy and in combination therapy and more commonly than in patients treated with placebo, were upper respiratory tract infection, nasopharyngitis, and headache.

Before prescribing JANUVIA® (sitagliptin) tablets, please read the accompanying Prescribing Information. The Medication Guide also is available.