e premenopausal anovulatory women. As a result, these patients may be at an increased risk for pregnancy while taking OSENI [see Use in Specific Populations (8.1)]. This effect has not been investigated in clinical trials, so the frequency of this occurrence is not known. Adequate contraception in all premenopausal women treated with OSENI is recommended.
5.11 Macrovascular Outcomes
There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with OSENI or any other antidiabetic drug.
6 ADVERSE REACTIONS6.1 Clinical Studies 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 clinical practice.
Alogliptin and Pioglitazone
Over 1500 patients with type 2 diabetes have received alogliptin coadministered with pioglitazone in four large, randomized, double-blind, controlled clinical trials. The mean exposure to OSENI was 29 weeks with more than 100 subjects treated for more than one year. The studies consisted of two placebo-controlled studies of 16 to 26 weeks in duration and two active-controlled studies of 26 weeks and 52 weeks in duration. In the OSENI arm, the mean duration of diabetes was approximately six years, the mean body mass index (BMI) was 31 kg/m2 (54% of patients had a BMI ≥30 kg/m2), and the mean age was 54 years (16% of patients ≥65 years of age).
In a pooled analysis of these four controlled clinical studies, the overall incidence of adverse events was 65% in patients treated with OSENI compared to 57% treated with placebo. Overall discontinuation of therapy due to adverse events was 2.5% with OSENI compared to 2.0% with placebo, 3.7% with pioglitazone or 1.3% with alogliptin.
Adverse reactions reported in ≥4% of patients treated with OSENI and more frequently than in patients who received alogliptin, pioglitazone or placebo are summarized in Table 1.
Table 1. Adverse Reactions Reported in ≥4% of Patients Treated with OSENI and More Frequently than in Patients Receiving Either Alogliptin, Pioglitazone or Placebo
Number of Patients (%)
OSENI *
Alogliptin †
Pioglitazone ‡
Placebo
N=1533
N=446
N=949
N=153
Nasopharyngitis
75 (4.9)
21 (4.7)
37 (3.9)
6 (3.9)
Back Pain
64 (4.2)
9 (2.0)
32 (3.4)
5 (3.3)
Upper Respiratory Tract Infection
63 (4.1)
19 (4.3)
26 (2.7)
5 (3.3)
OSENI – includes data pooled for patients receiving alogliptin 25 mg and 12.5 mg combined with pioglitazone 15 mg, 30 mg and 45 mg
Alogliptin – includes data pooled for patients receiving alogliptin 25 mg and 12.5 mg
Pioglitazone – includes data pooled for patients receiving pioglitazone 15 mg, 30 mg and 45 mg
Alogliptin Add-On Therapy to a Thiazolidinedione
In addition, in a 26-week, placebo-controlled, double-blind study, patients inadequately controlled on a thiazolidinedione alone or in combination with metformin or a sulfonylurea were treated with add-on alogliptin therapy or placebo; the adverse reactions reported in ≥5% of patients and more frequently than in pat
