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Sitagliptin in Type 2 Diabetes: Great Safety and Tolerability

A new pooled analysis shows DPP-4 inhibitors have a greater safety and tolerability profile when compared to other antihyperglycemic agents….

DPP-4 inhibitors like sitagliptin have a greater safety and tolerability profile when compared to other antihyperglycemic agents. They have lower risk of hypoglycemia, less effects on weight, and excellent tolerability when compared to other classes of antihyperglycemic drugs. However, it is important to continue monitoring the safety and tolerability of this newer class of drugs. There have been previous analyses studying the treatment of type 2 diabetes with sitagliptin and how well it is tolerated but Samuel S. Engel et. al. performed a more recent pooled analysis including data from 14,611 patients in 25 different studies with type 2 diabetic patients who received either sitagliptin or a comparator agent. The results of this analysis were published in December 2011. These randomized, controlled, double-blind trials (RCTs) were conducted by Merck and patients in the exposed group received sitagliptin 100 mg daily for between 12 weeks and 2 years. The patient data was taken from each study used in the pooled analysis to evaluate between-group differences in adverse effects (AEs).

Table 1: Adverse Effects of Interest

AE
Incidence
Hypoglycemia

Between group difference of -6.2 events per 100 patient-years

[sitagliptin < comparator (mainly sulfonylureas)]
GI Symptoms

Abdominal pain, nausea, and vomiting (sitagliptin ~ comparator)

Constipation (sitagliptin > comparator)
Diarrhea [sitagliptin < comparator (mainly metformin)]
Major Cardiovascular Event (MACE)

Exposure-adjusted incidence of MACE was 0.65 per 100 patient-years in sitagliptin group and 0.74 per 100 patient-years in the comparator group. (sitagliptin < comparator)

Neoplasms

Basal cell carcinoma, prostate cancer, breast cancer, and pancreatic cancer were most common but rare. There was a 0.90 per 100 patient-years incidence in sitagliptin group and 0.93 per 100 patient years in comparator group.

(sitagliptin < comparator)
Sitagliptin had a higher rate of non-malignant neoplasms.
Angioedema

Exposure-adjusted incidence of events was 0.99 per 100 patient-years in the sitagliptin group and 1.35 in the comparator group for patients treated concomitantly with ACE inhibitors. For patients not treated with ACE inhibitors the incidence rates were 1.14 for the sitagliptin group and 1.16 for the comparator group.

Other Composite Endpoints

Pancreatitis (sitagliptin ~ comparator)

Acute Renal Failure (sitagliptin ~ comparator)

Bronchitis, Pneumonia, Upper Respiratory Infection, and Urinary Tract Infections (sitagliptin ~ comparator)

Rash (sitagliptin > comparator)

Atrial Fibrillation (sitagliptin > comparator)

 

After assessment of this newer pooled analysis, sitagliptin still shows higher safety and excellent tolerability when compared to other antihyperglycemic agents.

Engel, Samuel S., Elizabeth Round, Gregory T. Golm, Keith D. Kaufman, and Barry J. Goldstein. "Safety and Tolerability of Sitagliptin in Type 2 Diabetes: Pooled Analysis of 25 Clinical Studies." National Center for Biotechnology Information. U.S. National Library of Medicine, 23 May 2013. Web. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3687098/.