JANUVIA®

(sitagliptin) tablets

Efficacy Profile

Initiating basal insulin

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

In a study comparing the efficacy and safety of continuing JANUVIA during insulin glargine initiation and uptitration vs discontinuation of JANUVIA in patients with type 2 diabetes

Greater A1C reductions when JANUVIA® (sitagliptin) and metformin were maintained during insulin glargine initiation and uptitration1

Primary end point: A1C reductions at week 30 (mean baseline A1C: 8.8%)a,b,c

A1C Data for Sitagliptin and Metformin and Adding Insulin Glargine

Placebo + insulin glargine

(withdrawl of JANUVIA) n=370

JANUVIA + insulin glargine

100 mg once daily n=370

All patients were on a stable dose of metformin ≥ 1500 mg/day. JANUVIA was maintained at 100 mg once daily. All patients initiated insulin glargine at a starting dose of 10 units.

aFAS population.

bLS mean (95% CI) change from baseline.

cThe between-group difference (95% CI) and P-value are model-based.

LS, least squares; FAS, full-analysis-set.

Back to top  | Study design below

More patients reached A1C goal of <7% when JANUVIA® (sitagliptin) and metformin were maintained during insulin glargine initiation and uptitration1

Secondary end point: A1C <7% at week 30a

A1C Goal Data for Sitagliptin and Metformin and Adding Insulin Glargine

All patients were on a stable dose of metformin ≥ 1500 mg/day. JANUVIA was maintained at 100 mg once daily. All patients initiated insulin glargine at a starting dose of 10 units.

aFAS population.

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

12.2% for patients treated with JANUVIA + glimepiride ± metformin vs 1.8% for placebo + glimepiride ± metformin; 15.5% for patients treated with JANUVIA + 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.

Study Design:

30-week study comparing the maintenance of sitagliptin plus metformin during insulin glargine initiation and uptitration vs withdrawal of sitagliptin:
A multinational, randomized, double-blind, placebo-controlled, parallel-group study to assess the effect of continuing sitagliptin at a dose of 100 mg once daily (n=373) relative to withdrawing sitagliptin (n=370) was conducted in patients ≥18 years of age with type 2 diabetes, eGFR ≥60 mL/min/1.73 m2, and inadequate glycemic control who were initiating and uptitrating insulin glargine over 30 weeks. The primary efficacy end point was A1C change from baseline relative to placebo (sitagliptin withdrawal). All patients were on a stable dose of metformin ≥1500 mg/day throughout the study. The mean duration of diabetes was >10 years.1

eGFR, estimated glomerular filtration rate.

Indication

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 Safety Information

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.

An association between dipeptidyl peptidase-4 (DPP-4) inhibitor treatment and heart failure has been observed in cardiovascular outcomes trials for two other members of the DPP-4 inhibitor class. These trials evaluated patients with type 2 diabetes mellitus and atherosclerotic cardiovascular disease. Consider the risks and benefits of JANUVIA prior to initiating treatment in patients at risk for heart failure, such as those with a prior history of heart failure and a history of renal impairment, and observe these patients for signs and symptoms of heart failure during therapy. Advise patients of the characteristic symptoms of heart failure and to immediately report such symptoms. If heart failure develops, evaluate and manage according to current standards of care and consider discontinuation of 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 impairment 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 impairment, 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 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.

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.

Reference

1. Roussel R, Duran-Garcia S, Zhang Y, et al. Double-blind, randomized clinical trial comparing the efficacy and safety of continuing or discontinuing the dipeptidyl peptidase-4 inhibitor sitagliptin when initiating insulin glargine therapy in patients with type 2 diabetes: The CompoSIT-I Study. Diabetes Obes Metab. 2019;21(4):781-790.

US-DIA-0169004/20