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

JANUVIA: Strong A1C lowering similar to glipizide in patients with moderate to severe renal insufficiency1,2

Clinical Trial Data in Patients With Moderate to Severe Renal Insufficiency

a PP population; bA –0.11% between-group difference (95% CI, –0.29% to 0.06%); cDosage of JANUVIA was 50 mg once daily for patients with moderate renal insufficiency and 25 mg once daily for patients with severe renal insufficiency; dThe mean dose of glipizide was 7.7 mg/day in the PP population.

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Similar A1C reductions vs glipizide in the FAS/LOCF population at 54 weeks2

  • In the FAS/LOCF population (n=407), patients treated with JANUVIA 25 mg or 50 mg once daily (n=202) achieved LS mean A1C reductions from baseline comparable to glipizide ≥2.5 mg/day–≤20 mg/day (n=205): JANUVIA –0.4% (mean baseline A1C: 7.8%); glipizide –0.5% (mean baseline A1C: 7.9%)
  • A conclusion in favor of the noninferiority of JANUVIA to glipizide may be limited to patients with baseline A1C comparable to those included in the study

Select adverse events reported in this study1

  • Incidences of overall adverse events were similar between the 2 treatment groups, except for neoplasms and metabolic disorders (due to differences in hypoglycemia). With regard to neoplasms, 6 patients with neoplasms were reported in the sitagliptin group and none in the glipizide group. Of the 6 events reported, 3 were confirmed malignant disease, and 3 were either nonmalignant or not histologically confirmed. Each event was identified within the first 6 months of initiating the study drug, comprised a different type of lesion (breast cancer, chronic myeloid leukemia, lung cancer, pancreatic head mass, polycythemia vera, and thyroid nodule), and determined unrelated to study drug by investigators
  • Similar decreases from baseline in estimated glomerular filtration rate (eGFR) were observed at week 54 in both treatment groups (sitagliptin, –3.9 mL/min/1.73 m2; glipizide, –3.3 mL/min/1.73 m2)
  • 28 of 149 (18.8%) patients in the sitagliptin group and 17 of 154 (11.0%) patients in the glipizide group transitioned from moderate to severe renal insufficiency status during the study

LS = least squares; PP = per-protocol; CI = confidence interval; FAS = full-analysis-set; LOCF = last-observation-carried-forward.

In the same study, significantly less hypoglycemia compared with glipizide in patients with moderate to severe renal insufficiency1

In 54 Week Study, Hypoglycemia Results vs Glipizide in Patients With Moderate to Severe Renal Insufficiency

e Percentage of patients experiencing one or more episodes of hypoglycemia; fAll-patients-as-treated (APaT) population; P=0.001 for between-group difference.

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When added to a sulfonylurea (glimepiride) or insulin, patients treated with sitagliptin experienced increased incidence of hypoglycemia

  • 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

In a separate 54-week study of patients with type 2 diabetes and ESRD on dialysis3,4

  • Provided A1C reductions (primary end point): The group treated with JANUVIA (25 mg once daily; n=59) had a 0.7% A1C reduction from baseline. The glipizide group (2.5 mg–20 mg/day; mean dose: 5.3 mg/day; n=62) had a 0.9% A1C reduction from baseline; mean baseline A1C 7.8%
  • Incidences of overall adverse events were similar between the 2 treatment groups, except for cellulitis and headache which occurred more frequently in the sitagliptin group compared to the glipizide group. A total of 10 patients died during the study: 4 in the sitagliptin group and 6 in the glipizide group

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ESRD = end-stage renal disease

References: 1. Arjona Ferreira JC, Marre M, Barzilai N, et al. Efficacy and safety of sitagliptin versus glipizide in patients with type 2 diabetes and moderate-to-severe chronic renal insufficiency. Diabetes Care. 2013;36(5):1067–1073. 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-1082334-0003. 3. Arjona Ferreira JC, Corry D, Mogensen CE, et al. Efficacy and safety of sitagliptin in patients with type 2 diabetes and ESRD receiving dialysis: a 54-week randomized trial. Am J Kidney Dis. 2013;61(4):579–587. 4. Data available on request from Merck, Professional Services-DAP, WP1-27, PO Box 4, West Point, PA 19486-0004. Please specify information package DIAB-1082335-0000.

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.

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.

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.

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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.

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.