Included as part of the "PRECAUTIONS" Section
Risk Of Thyroid C-Cell Tumors
Liraglutide, one of the components of XULTOPHY 100/3.6, causes dose-dependent and treatment-durationdependent
thyroid C-cell tumors (adenomas and/or carcinomas) at clinically relevant exposures in both
genders of rats and mice [see Nonclinical Toxicology]. Malignant thyroid C-cell carcinomas were
detected in rats and mice. It is unknown whether XULTOPHY 100/3.6 will cause thyroid C-cell tumors,
including medullary thyroid carcinoma (MTC), in humans, as the human relevance of liraglutide-induced
rodent thyroid C-cell tumors has not been determined.
Cases of MTC in patients treated with liraglutide have been reported in the postmarketing period; the data in
these reports are insufficient to establish or exclude a causal relationship between MTC and liraglutide use in
XULTOPHY 100/3.6 is contraindicated in patients with a personal or family history of MTC or in patients
with MEN 2. Counsel patients regarding the potential risk for MTC with the use of XULTOPHY 100/3.6 and
inform them of symptoms of thyroid tumors (e.g. a mass in the neck, dysphagia, dyspnea, persistent
Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection
of MTC in patients treated with XULTOPHY 100/3.6. Such monitoring may increase the risk of unnecessary
procedures, due to low test specificity for serum calcitonin and a high background incidence of thyroid
disease. Significantly elevated serum calcitonin may indicate MTC and patients with MTC usually have
calcitonin values >50 ng/L. If serum calcitonin is measured and found to be elevated, the patient should be
further evaluated. Patients with thyroid nodules noted on physical examination or neck imaging should also
be further evaluated.
Based on spontaneous postmarketing reports, acute pancreatitis, including fatal and non-fatal hemorrhagic or
necrotizing pancreatitis, has been observed in patients treated with liraglutide, one of the components of
XULTOPHY 100/3.6. In glycemic control trials of liraglutide, there have been 13 cases of pancreatitis
among liraglutide-treated patients and 1 case in a comparator (glimepiride) treated patient (2.7 vs. 0.5 cases
per 1000 patient-years). Nine of the 13 cases with liraglutide were reported as acute pancreatitis and four
were reported as chronic pancreatitis. In one case in a liraglutide-treated patient, pancreatitis, with necrosis,
was observed and led to death; however clinical causality could not be established. Some patients had other
risk factors for pancreatitis, such as a history of cholelithiasis or alcohol abuse.
After initiation of XULTOPHY 100/3.6, observe patients carefully for signs and symptoms of pancreatitis
(including persistent severe abdominal pain, sometimes radiating to the back and which may or may not be
accompanied by vomiting). If pancreatitis is suspected, XULTOPHY 100/3.6 should promptly be
discontinued and appropriate management should be initiated. If pancreatitis is confirmed, restarting
XULTOPHY 100/3.6 is not recommended.
Liraglutide, one of the components of XULTOPHY 100/3.6, has been studied in a limited number of patients
with a history of pancreatitis. It is unknown if patients with a history of pancreatitis are at higher risk for
development of pancreatitis on liraglutide.
Never Share A Xultophy 100/3.6 Pen Between Patients
XULTOPHY 100/3.6 pen must never be shared between patients, even if the needle is changed. Sharing of
the pen poses a risk for transmission of blood-borne pathogens.
Hyperglycemia Or Hypoglycemia With Changes In Xultophy 100/3.6 Regimen
Changes in XULTOPHY 100/3.6 regimen may affect glycemic control and predispose to hypoglycemia or
hyperglycemia [see Overdose Due To Medication Errors]. These changes should be made cautiously and only
under medical supervision and the frequency of blood glucose monitoring should be increased. Adjustments
in concomitant oral anti-diabetic treatment may be needed. When initiating XULTOPHY 100/3.6, follow
dosing recommendations [see DOSAGE AND ADMINISTRATION].
Overdose Due To Medication Errors
XULTOPHY 100/3.6 contains two drugs: insulin degludec and liraglutide. Administration of more than 50
units of XULTOPHY 100/3.6 daily can result in overdose of the liraglutide component. Do not exceed the
1.8 mg maximum recommended dose of liraglutide or use with other glucagon-like peptide-1 receptor
Accidental mix-ups between insulin products have been reported. To avoid medication errors between
XULTOPHY 100/3.6 (an insulin containing product) and other insulin products, instruct patients to always
check the label before each injection.
Hypoglycemia is the most common adverse reaction of insulin containing products, including XULTOPHY
100/3.6 [see ADVERSE REACTIONS]. Severe hypoglycemia can cause seizures, may be life-threatening or
cause death. Hypoglycemia can impair concentration ability and reaction time; this may place an individual
and others at risk in situations where these abilities are important (e.g., driving or operating other
machinery). XULTOPHY 100/3.6 (an insulin-containing product) or any insulin, should not be used during
episodes of hypoglycemia [see CONTRAINDICATIONS].
Hypoglycemia can happen suddenly and symptoms may differ in each individual and change over time in the
same individual. Symptomatic awareness of hypoglycemia may be less pronounced in patients with
longstanding diabetes, in patients with diabetic nerve disease, in patients using medications that block the
sympathetic nervous system (e.g., beta-blockers) [see DRUG INTERACTIONS], or in patients who experience
Risk Factors For Hypoglycemia
The risk of hypoglycemia generally increases with intensity of glycemic control. The risk of hypoglycemia
after an injection is related to the duration of action of the insulin [see CLINICAL PHARMACOLOGY] and, in
general, is highest when the glucose lowering effect of the insulin is maximal. As with all insulin containing
products, the glucose lowering effect time course of XULTOPHY 100/3.6 may vary among different
individuals or at different times in the same individual and depends on many conditions, including the area
of injection as well as the injection site blood supply and temperature.
Other factors which may increase the risk of hypoglycemia include changes in meal pattern (e.g.,
macronutrient content or timing of meals), changes in level of physical activity, or changes to co-
administered medication [see DRUG INTERACTIONS]. Patients with renal or hepatic impairment may be at
higher risk of hypoglycemia [see Use In Specific Populations].
Risk Mitigation Strategies For Hypoglycemia
Patients and caregivers must be educated to recognize and manage hypoglycemia. Self-monitoring of blood
glucose plays an essential role in the prevention and management of hypoglycemia. In patients at higher risk
for hypoglycemia and patients who have reduced symptomatic awareness of hypoglycemia, increased
frequency of blood glucose monitoring is recommended.
Acute Kidney Injury
There have been postmarketing reports of acute renal failure and worsening of chronic renal failure, which
may sometimes require hemodialysis in patients treated with liraglutide, one of the components of
XULTOPHY 100/3.6 [see ADVERSE REACTIONS]. Some of these events were reported in patients without
known underlying renal disease. A majority of the reported events occurred in patients who had experienced
nausea, vomiting, diarrhea, or dehydration. Some of the reported events occurred in patients receiving one or
more medications known to affect renal function or hydration status. Altered renal function has been
reversed in many of the reported cases with supportive treatment and discontinuation of potentially causative
agents, including liraglutide. Advise patients of the potential risk of dehydration due to gastrointestinal
adverse reactions and take precautions to avoid fluid depletion.
Hypersensitivity And Allergic Reactions
Severe, life-threatening, generalized allergy, including anaphylaxis, angioedema, bronchospasm,
hypotension, and shock can occur with XULTOPHY 100/3.6. Allergic reactions (manifested with signs and
symptoms such as urticaria, rash, pruritus) have been reported with XULTOPHY 100/3.6. There have been
postmarketing reports of serious hypersensitivity reactions (e.g., anaphylactic reactions and angioedema) in
patients treated with liraglutide, one of the components of XULTOPHY 100/3.6 [see ADVERSE REACTIONS]. If a hypersensitivity reaction occurs, discontinue XULTOPHY 100/3.6; treat promptly per standard of
care, and monitor until signs and symptoms resolve.
Anaphylaxis and angioedema have been reported with other GLP-1 receptor agonists. Use caution in a
patient with a history of anaphylaxis or angioedema with another GLP-1 receptor agonist because it is
unknown whether such patients will be predisposed to these reactions with XULTOPHY 100/3.6.
XULTOPHY 100/3.6 is contraindicated in patients who have had hypersensitivity reactions to insulin
degludec, liraglutide or one of the excipients of these products [see CONTRAINDICATIONS].
Acute Gallbladder Disease
In a cardiovascular outcomes trial (LEADER trial) [see Clinical Studies], 3.1% of patients treated with
liraglutide, one of the components of XULTOPHY 100/3.6, versus 1.9% of placebo treated patients reported an
acute event of gallbladder disease, such as cholelithiasis or cholecystitis. The majority of events required
hospitalization or cholecystectomy. If cholelithiasis is suspected, gallbladder studies and appropriate clinical
follow-up are indicated.
All insulin-containing products, including XULTOPHY 100/3.6, cause a shift in potassium from the
extracellular to intracellular space, possibly leading to hypokalemia. Untreated hypokalemia may cause
respiratory paralysis, ventricular arrhythmia, and death. Monitor potassium levels in patients at risk for
hypokalemia if indicated (e.g., patients using potassium-lowering medications, patients taking medications
sensitive to serum potassium concentrations).
Fluid Retention And Congestive Heart Failure With Concomitant Use Of A PPAR Gamma Agonist
Thiazolidinediones (TZDs), which are peroxisome proliferator-activated receptor (PPAR)-gamma agonists
can cause dose related fluid retention, particularly when used in combination with insulin containing
products, including XULTOPHY 100/3.6. Fluid retention may lead to or exacerbate congestive heart failure.
Patients treated with insulin containing products, including XULTOPHY 100/3.6 and a PPAR-gamma
agonist should be observed for signs and symptoms of congestive heart failure. If congestive heart failure
develops, it should be managed according to current standards of care and discontinuation or dose reduction
of the PPAR-gamma agonist must be considered.
Patient Counseling Information
Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use)
Risk Of Thyroid C-Cell Tumors
Inform patients that liraglutide, one of the components of XULTOPHY 100/3.6, causes benign and
malignant thyroid C-cell tumors in mice and rats and that the human relevance of this finding is unknown.
Patients should be counseled to report symptoms of thyroid tumors (e.g., a lump in the neck, hoarseness,
dysphagia or dyspnea) to their physician [see BOX WARNING and WARNINGS AND PRECAUTIONS].
Dehydration And Renal Failure
Advise patients of the potential risk of dehydration due to gastrointestinal adverse reactions and take
precautions to avoid fluid depletion. Patients should be informed of the potential risk for worsening renal
function, which in some cases may require dialysis [see WARNINGS AND PRECAUTIONS].
Inform patients of the potential risk for pancreatitis. Explain that persistent severe abdominal pain that may
radiate to the back and which may or may not be accompanied by vomiting, is the hallmark symptom of
acute pancreatitis. Instruct patients to discontinue XULTOPHY 100/3.6 promptly and contact their physician
if persistent severe abdominal pain occurs [see WARNINGS AND PRECAUTIONS].
Acute Gallbladder Disease
Inform patients of the potential risk for cholelithiasis or cholecystitis. Instruct patients to contact their physician if
cholelithiasis or cholecystitis is suspected for appropriate clinical follow-up.
Overdose Due To Medication Errors
Inform patients that XULTOPHY 100/3.6 contains two drugs: insulin degludec and liraglutide. Accidental
mix-ups between insulin products have been reported. To avoid medication errors between XULTOPHY
100/3.6 (an insulin containing product) and other insulin products, instruct patients to always check the label
before each injection.
Advise patients that the administration of more than 50 units of XULTOPHY 100/3.6 daily can result in
overdose of the liraglutide component. Instruct patients not to administer concurrently with other glucagonlike
peptide-1 receptor agonists.
Hyperglycemia Or Hypoglycemia
Inform patients that hypoglycemia is the most common adverse reaction with insulin products. Inform
patients of the symptoms of hypoglycemia. Inform patients that the ability to concentrate and react may be
impaired as a result of hypoglycemia. This may present a risk in situations where these abilities are
especially important, such as driving or operating other machinery. Advise patients who have frequent
hypoglycemia or reduced or absent warning signs of hypoglycemia to use caution when driving or operating
Advise patients that changes in XULTOPHY 100/3.6 regimen can predispose to hyper- or hypoglycemia.
Advise patients that changes in XULTOPHY 100/3.6 regimen should be made under close medical
supervision [see WARNINGS AND PRECAUTIONS].
Never Share A Xultophy 100/3.6 Pen Between Patients
Advise patients that they must never share a XULTOPHY 100/3.6 pen with another person, even if the
needle is changed, because doing so carries a risk for transmission of blood-borne pathogens.
Inform patients that serious hypersensitivity reactions have been reported during postmarketing use of
liraglutide, one of the components of XULTOPHY 100/3.6.
If symptoms of hypersensitivity reactions occur, patients must stop taking XULTOPHY 100/3.6 and seek
medical advice promptly [see WARNINGS AND PRECAUTIONS].
Inform patients that hepatobiliary disorders including elevations of liver enzymes, hyperbilirubinemia,
cholestasis, and hepatitis have been reported during postmarketing use of liraglutide. Instruct patients to
contact their physician if they develop jaundice.
Instruct female patients of reproductive potential to inform their healthcare provider of a known or suspected
pregnancy [see Use In Specific Populations].
Carcinogenesis, Mutagenesis, Impairment Of Fertility
No studies have been conducted with the XULTOPHY 100/3.6 combination to evaluate carcinogenesis,
mutagenesis or impairment of fertility. The following data are based upon studies with insulin degludec and
Standard 2-year carcinogenicity studies in animals have not been performed to evaluate the carcinogenic
potential of insulin degludec.
In a 52-week study including human insulin (NPH insulin) as comparator, Sprague-Dawley rats were dosed
subcutaneously with insulin degludec at 3.3, 6.7, and 10 U/kg/day, resulting in 5 times the human exposure
(AUC) when compared to a human subcutaneous dose of 0.75 U/kg/day. Human insulin was dosed at 6.7
U/kg/day. No treatment-related increases in incidences of hyperplasia, benign or malignant tumors were
recorded in female mammary glands from rats dosed with insulin degludec and no treatment related changes
in the female mammary gland cell proliferation were found using BrdU incorporation. Further, no treatment
related changes in the occurrence of hyperplastic or neoplastic lesions were seen in any animals dosed with
insulin degludec when compared to vehicle or human insulin.
Genotoxicity testing of insulin degludec was not performed.
In a combined fertility and embryo-fetal study in male and female rats, treatment with insulin degludec up to
21 U/kg/day (approximately 5 times the human subcutaneous dose of 0.75 U/kg/day, based on U/body
surface area) prior to mating and in female rats during gestation had no effect on mating performance and
A 104-week carcinogenicity study was conducted in male and female CD-1 mice at doses of 0.03, 0.2, 1.0,
and 3.0 mg/kg/day liraglutide administered by bolus subcutaneous injection yielding systemic exposures
0.2-, 2-, 10- and 45-times the human exposure, respectively, at the MRHD of 1.8 mg/day based on plasma
AUC comparison. A dose-related increase in benign thyroid C-cell adenomas was seen in the 1.0 and the 3.0
mg/kg/day groups with incidences of 13% and 19% in males and 6% and 20% in females, respectively. Ccell
adenomas did not occur in control groups or 0.03 and 0.2 mg/kg/day groups. Treatment-related
malignant C-cell carcinomas occurred in 3% of females in the 3.0 mg/kg/day group. Thyroid C-cell tumors
are rare findings during carcinogenicity testing in mice. A treatment-related increase in fibrosarcomas was
seen on the dorsal skin and subcutis, the body surface used for drug injection, in males in the 3 mg/kg/day
group. These fibrosarcomas were attributed to the high local concentration of drug near the injection site.
The liraglutide concentration in the clinical formulation (6 mg/mL) is 10-times higher than the concentration
in the formulation used to administer 3 mg/kg/day liraglutide to mice in the carcinogenicity study (0.6
A 104-week carcinogenicity study was conducted in male and female Sprague Dawley rats at doses of 0.075,
0.25 and 0.75 mg/kg/day liraglutide administered by bolus subcutaneous injection with exposures 0.5-, 2-
and 8-times the human exposure, respectively, resulting from the MRHD based on plasma AUC
comparison. A treatment-related increase in benign thyroid C-cell adenomas was seen in males in 0.25 and
0.75 mg/kg/day liraglutide groups with incidences of 12%, 16%, 42%, and 46% and in all female liraglutidetreated
groups with incidences of 10%, 27%, 33%, and 56% in 0 (control), 0.075, 0.25, and 0.75 mg/kg/day
groups, respectively. A treatment-related increase in malignant thyroid C-cell carcinomas was observed in all
male liraglutide-treated groups with incidences of 2%, 8%, 6%, and 14% and in females at 0.25 and 0.75
mg/kg/day with incidences of 0%, 0%, 4%, and 6% in 0 (control), 0.075, 0.25, and 0.75 mg/kg/day groups,
respectively. Thyroid C-cell carcinomas are rare findings during carcinogenicity testing in rats.
Studies in mice demonstrated that liraglutide-induced C-cell proliferation was dependent on the GLP-1
receptor and that liraglutide did not cause activation of the REarranged during Transfection (RET) protooncogene
in thyroid C-cells.
Human relevance of thyroid C-cell tumors in mice and rats is unknown and has not been determined by
clinical studies or nonclinical studies [see BOX WARNING and WARNINGS AND PRECAUTIONS].
Liraglutide was negative with and without metabolic activation in the Ames test for mutagenicity and in a
human peripheral blood lymphocyte chromosome aberration test for clastogenicity. Liraglutide was negative
in repeat-dose in vivo micronucleus tests in rats.
In rat fertility studies using subcutaneous doses of 0.1, 0.25 and 1.0 mg/kg/day liraglutide, males were
treated for 4 weeks prior to and throughout mating and females were treated 2 weeks prior to and throughout
mating until gestation day 17. No direct adverse effects on male fertility was observed at doses up to 1.0
mg/kg/day, a high dose yielding an estimated systemic exposure 11- times the human exposure at the
MRHD, based on plasma AUC. In female rats, an increase in early embryonic deaths occurred at 1.0
mg/kg/day. Reduced body weight gain and food consumption were observed in females at the 1.0 mg/kg/day
Use In Specific Populations
Based on animal reproduction studies, there may be risks to the fetus from exposure to liraglutide during
pregnancy. XULTOPHY 100/3.6 should be used during pregnancy only if the potential benefit justifies the
potential risk to the fetus.
There are no available data with XULTOPHY 100/3.6, insulin degludec or liraglutide in pregnant women to
inform a drug associated risk for major birth defects and miscarriage. There are clinical considerations
regarding the risks of poorly controlled diabetes in pregnancy [see Clinical Considerations].
For insulin degludec, rats and rabbits were exposed in animal reproduction studies at 5 times (rat) and 10
times (rabbit) the human exposure at a dose of 0.75 U/kg/day. No adverse outcomes were observed for
pregnant animals and offspring [see Data].
For liraglutide, animal reproduction studies identified increased adverse developmental outcomes from
exposure during pregnancy. Liraglutide exposure was associated with early embryonic deaths and an
imbalance in some fetal abnormalities in pregnant rats administered liraglutide during organogenesis at doses
that approximate clinical exposures at the maximum recommended human dose (MRHD) of 1.8 mg/day. In
pregnant rabbits administered liraglutide during organogenesis, decreased fetal weight and an increased
incidence of major fetal abnormalities were seen at exposures below the human exposures at the MRHD [see
The estimated background risk of major birth defects is 6–10% in women with pre-gestational diabetes with
an HbA1c >7 and has been reported to be as high as 20–25% in women with a HbA1c >10. The estimated
background risk of miscarriage for the indicated population is unknown. In the U.S. general population, the
estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–
4% and 15–20%, respectively.
Disease-associated maternal and/or embryo/fetal risk
Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia,
spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes mellitus
increases the fetal risk for major birth defects, stillbirth, macrosomia related morbidity.
Insulin degludec was investigated in studies covering fertility, embryo-fetal development and pre- and postnatal
development in rats and during the period of embryofetal development in rabbits. Human insulin (NPH
insulin) was included as comparator. In these studies insulin degludec was given subcutaneously at up to 21
U/kg/day in rats and 3.3 U/kg/day in rabbits, resulting in 5 times (rat) and 10 times (rabbit) the human
exposure (AUC) at a human subcutaneous dose of 0.75 U/kg/day. Overall the effects of insulin degludec
were similar to those observed with human insulin.
Female rats given subcutaneous doses of 0.1, 0.25 and 1.0 mg/kg/day liraglutide beginning 2 weeks before
mating through gestation day 17 had estimated systemic exposures 0.8-, 3-, and 11-times the human
exposure at the MRHD based on plasma AUC comparison. The number of early embryonic deaths in the 1
mg/kg/day group increased slightly. Fetal abnormalities and variations in kidneys and blood vessels,
irregular ossification of the skull, and a more complete state of ossification occurred at all doses. Mottled
liver and minimally kinked ribs occurred at the highest dose. The incidence of fetal malformations in
liraglutide-treated groups exceeding concurrent and historical controls were misshapen oropharynx and/or
narrowed opening into larynx at 0.1 mg/kg/day and umbilical hernia at 0.1 and 0.25 mg/kg/day.
Pregnant rabbits given subcutaneous doses of 0.01, 0.025 and 0.05 mg/kg/day liraglutide from gestation day
6 through day 18 inclusive, had estimated systemic exposures less than the human exposure at the MRHD of
1.8 mg/day at all doses, based on plasma AUC. Liraglutide decreased fetal weight and dose dependently
increased the incidence of total major fetal abnormalities at all doses. The incidence of malformations
exceeded concurrent and historical controls at 0.01 mg/kg/day (kidneys, scapula), ≥ 0.01 mg/kg/day (eyes,
forelimb), 0.025 mg/kg/day (brain, tail and sacral vertebrae, major blood vessels and heart, umbilicus), ≥
0.025 mg/kg/day (sternum) and at 0.05 mg/kg/day (parietal bones, major blood vessels). Irregular
ossification and/or skeletal abnormalities occurred in the skull and jaw, vertebrae and ribs, sternum, pelvis,
tail, and scapula; and dose-dependent minor skeletal variations were observed. Visceral abnormalities
occurred in blood vessels, lung, liver, and esophagus. Bilobed or bifurcated gallbladder was seen in all
treatment groups, but not in the control group.
In pregnant female rats given subcutaneous doses of 0.1, 0.25 and 1.0 mg/kg/day liraglutide from gestation
day 6 through weaning or termination of nursing on lactation day 24, estimated systemic exposures were
0.8-, 3-, and 11-times human exposure at the MRHD of 1.8 mg/day, based on plasma AUC. A slight delay in
parturition was observed in the majority of treated rats. Group mean body weight of neonatal rats from
liraglutide-treated dams was lower than neonatal rats from control group dams. Bloody scabs and agitated
behavior occurred in male rats descended from dams treated with 1 mg/kg/day liraglutide. Group mean body
weight from birth to postpartum day 14 trended lower in F2 generation rats descended from liraglutidetreated
rats compared to F2 generation rats descended from controls, but differences did not reach statistical
significance for any group.
There are no data on the presence of liraglutide or insulin degludec in human milk, the effects on the
breastfed infant, or the effects on milk production. In lactating rats, insulin degludec and liraglutide, the two
components of XULTOPHY 100/3.6, were present in milk.
The developmental and health benefits of breastfeeding should be considered along with the mother’s
clinical need for XULTOPHY 100/3.6 and any potential adverse effects on the breastfed infant from
XULTOPHY 100/3.6 or from the underlying maternal condition.
In lactating rats, insulin degludec was present in milk at a concentration lower than that in plasma.
In lactating rats, liraglutide was present unchanged in milk at concentrations approximately 50% of maternal
Safety and effectiveness of XULTOPHY 100/3.6 have not been established in pediatric patients.
Of the total number of 1881 subjects in clinical studies of XULTOPHY 100/3.6, 375 (19.9%) were 65 years
and over, while 52 (2.8%) were 75 years and over. No overall differences in safety or effectiveness were
observed between these subjects and younger subjects, and other reported clinical experience has not
identified differences in responses between the elderly and younger patients, but greater sensitivity of some
older individuals to the effects of XULTOPHY 100/3.6 cannot be ruled out.
Age had no clinically relevant effect on the pharmacokinetics of XULTOPHY 100/3.6 [see CLINICAL PHARMACOLOGY].
In elderly patients with diabetes, the initial dosing, dose increments, and maintenance dosage should be
conservative to avoid hypoglycemic reactions. Hypoglycemia may be more difficult to recognize in the
There is limited experience with XULTOPHY 100/3.6 in patients with mild and moderate renal impairment
and when used in these patients, additional glucose monitoring and XULTOPHY 100/3.6 dose adjustments
may be required on an individual basis. XULTOPHY 100/3.6 has not been studied in patients with severe
renal impairment [see WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY].
No clinically relevant difference in the pharmacokinetics of insulin degludec was identified in a study
comparing healthy subjects and subjects with renal impairment including subjects with end stage renal
The safety and efficacy of liraglutide was evaluated in a 26 week clinical study that included patients with
moderate renal impairment (eGFR 30 to 60 mL/min/1.73 m2). In the liraglutide treatment arm of a
cardiovascular outcomes trial (LEADER trial) [see Clinical Studies], 1932 (41.4%) patients had mild
renal impairment, 999 (21.4%) patients had moderate renal impairment and 117 (2.5%) patients had severe
renal impairment at baseline. No overall differences in safety or efficacy were seen in these patients
compared to patients with normal renal function.
There is limited experience with liraglutide in patients with end stage renal disease. There have been
postmarketing reports of acute renal failure and worsening of chronic renal failure, which may sometimes
require hemodialysis [see WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS].
XULTOPHY 100/3.6 has not been studied in patients with hepatic impairment.
No clinically relevant difference in the pharmacokinetics of insulin degludec, one of the components of
XULTOPHY 100/3.6, was identified in a study comparing healthy subjects and subjects with hepatic
impairment (mild, moderate, and severe hepatic impairment) [see CLINICAL PHARMACOLOGY].
There is limited experience in patients with mild, moderate or severe hepatic impairment with liraglutide,
one of the components of XULTOPHY 100/3.6 [see CLINICAL PHARMACOLOGY].
Liraglutide, one of the components of XULTOPHY 100/3.6, slows gastric emptying. XULTOPHY 100/3.6
has not been studied in patients with pre-existing gastroparesis.