In the 24-week, placebo-controlled factorial study of initial therapy with sitagliptin in combination with metformin, the incidence of hypoglycemia was 0.6% in patients given placebo, 0.6% in patients given sitagliptin alone, 0.8% in patients given metformin alone, and 1.6% in patients given sitagliptin in combination with metformin.

In the study of sitagliptin as initial therapy with pioglitazone, one patient taking sitagliptin experienced a severe episode of hypoglycemia. There were no severe hypoglycemia episodes reported in other studies except in the study involving coadministration with insulin.

Simvastatin

In the pre-marketing controlled clinical studies and their open-label extensions (2423 patients with median duration of follow-up of approximately 18 months), 1.4% of patients were discontinued due to adverse reactions. The most common adverse reactions that led to treatment discontinuation were: gastrointestinal disorders (0.5%), myalgia (0.1%), and arthralgia (0.1%). The most commonly reported adverse reactions (incidence ≥5%) in simvastatin controlled clinical trials were: upper respiratory infections (9.0%), headache (7.4%), abdominal pain (7.3%), constipation (6.6%), and nausea (5.4%).

Scandinavian Simvastatin Survival Study

In 4S involving 4444 patients (age range 35-71 years, 19% women, 100% Caucasians) treated with 20-40 mg/day of simvastatin (n=2221) or placebo (n=2223) over a median of 5.4 years, adverse reactions reported in ≥2% of patients and at a rate greater than placebo are shown in Table 5.

Table 5: Adverse Reactions Reported Regardless of Causality by ≥2% of Patients Treated with Simvastatin and Greater than Placebo in 4S   Simvastatin
(N = 2221)
% Placebo
(N = 2223)
%
Body as a Whole  
  Edema/swelling
  Abdominal pain 2.7
5.9 2.3
5.8
Cardiovascular System Disorders  
  Atrial fibrillation 5.7 5.1
Digestive System Disorders  
  Constipation
  Gastritis 2.2
4.9 1.6
3.9
Endocrine Disorders  
  Diabetes mellitus 4.2 3.6
Musculoskeletal Disorders  
  Myalgia 3.7 3.2
Nervous System/ Psychiatric Disorders  
  Headache
  Insomnia
  Vertigo 2.5
4.0
4.5 2.1
3.8
4.2
Respiratory System Disorders  
  Bronchitis
  Sinusitis 6.6
2.3 6.3
1.8
Skin / Skin Appendage Disorders  
  Eczema 4.5 3.0
Urogenital System Disorders  
  Infection, urinary tract 3.2 3.1

Heart Protection Study

In the Heart Protection Study (HPS), involving 20,536 patients (age range 40-80 years, 25% women, 97% Caucasians, 3% other races) treated with simvastatin 40 mg/day (n=10,269) or placebo (n=10,267) over a mean of 5 years, only serious adverse reactions and discontinuations due to any adverse reactions were recorded. Discontinuation rates due to adverse reactions were 4.8% in patients treated with simva