Use of a PPAR Gamma AgonistThiazolidinediones (TZDs), which are peroxisome proliferator-activated receptor (PPAR)-gamma agonists can cause dose related fluid retention, particularly when used in combination with insulin. Fluid retention may lead to or exacerbate congestive heart failure. Patients treated with insulin, including TRESIBA 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.
6 ADVERSE REACTIONS
The following adverse reactions are also discussed elsewhere:
•
Hypoglycemia [see Warnings and Precautions(5.3)]
•
Hypersensitivity and allergic reactions [see Warnings and Precautions (5.5)]
•
Hypokalemia [see Warnings and Precautions (5.6)]
6.1 Clinical Trial ExperienceBecause clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The safety of TRESIBA was eva luated in nine treat to target trials of 6-12 months duration, conducted in subjects with type 1 diabetes or type 2 diabetes [see Clinical Studies (14)].
The data in Table 1 reflect the exposure of 1102 patients with type 1 diabetes to TRESIBA with a mean exposure duration to TRESIBA of 34 weeks. The mean age was 43 years and 1% were older than 75 years. Fifty-seven percent were male, 81% were White, 2% were Black or African American and 4% were Hispanic. The mean body mass index (BMI) was 26 kg/m2. The mean duration of diabetes was 18 years and the mean HbA1c at baseline was 7.8%. A history of neuropathy, ophthalmopathy, nephropathy and cardiovascular disease at baseline was reported in 11%, 16%, 7% and 0.5% respectively. The mean eGFR at baseline was 87 mL/min/1.73 m2 and 7% of the patients had an eGFR less than 60 mL/min/1.73 m2.
The data in Table 2 reflect the exposure of 2713 patients with type 2 diabetes to TRESIBA with a mean exposure duration to TRESIBA of 36 weeks. The mean age was 58 years and 3% were older than 75 years. Fifty-eight percent were male, 71% were White, 7% were Black or African American and 13% were Hispanic. The mean BMI was 30 kg/m2. The mean duration of diabetes was 11 years and the mean HbA1c at baseline was 8.3%. A history of neuropathy, ophthalmopathy, nephropathy and cardiovascular disease at baseline was reported for 14%, 10%, 6% and 0.6% of participants respectively. At baseline, the mean eGFR was 83 mL/min/1.73 m2 and 9% had an eGFR less than 60 mL/min/1.73 m2.
Common adverse reactions (excluding hypoglycemia)occurring in TRESIBA treated subjects during clinical trials in patients with type 1 diabetes mellitus and type 2 diabetes mellitus are listed in Table 1 and Table 2, respectively. Common adverse reactions were defined as reactions occurring in ≥5% of the population studied. Hypoglycemia is not shown in these tables but discussed in a dedicated subsection below.
Table 1: Adverse Reactions Occurring in ≥5% of TRESIBA-Treated Patients with Type 1 Diabetes Mellitus
Adverse Reaction
TRESIBA
(n=1102)
Nasopharyngitis
23.9 %
Upper respiratory tract infection
11.9 %
Headache
11.8 %
Sinu
