Sitagliptin and cardiovascular outcomes

Bo Lively, Mercer University College of Pharmacy

Type 2 diabetes is a condition that results in impaired insulin secretion and insulin action. Diabetes is associated with many chronic complications. Cardiovascular disease in patients with diabetes is considered to be a major concern.1,2 The clinical effects of medication used in the treatment of diabetes are known; although, according to many physicians the risks that these medicines pose to other comorbidities is unknown.2

Sitagliptin phosphate is a dipeptidyl peptidase-4 (DPP-4) enzyme inhibitor, which exerts its activity in patients with type 2 diabetes by protecting the endogenous incretin hormones; therefore, the functions of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are enhanced and insulin release increased.3

Title: Effect of Sitagliptin on Cardiovascular Outcomes in Type 2 Diabetes
Design Randomized, double-blind study; N = 14,671
Objective To determine if any long-term effects on cardiovascular events exist with sitagliptin treatment in patients with type 2 diabetes
Study Groups Patients were randomized into two groups:

Sitagliptin drug therapy (100mg daily): (n = 7,332)

Placebo:                                                (n = 7,339)

Methods Eligible patients had type 2 diabetes with established cardiovascular disease and were at least 50 years of age, with a glycated hemoglobin level of 6.5 to 8.0% when treated with stable doses of one or two oral anti-hyperglycemic agents. Patients were randomized into a sitagliptin therapy group (100mg daily), or placebo group. The glycated hemoglobin level was measured at enrollment, four months, eight months, and then annually.
Duration July 2012-March 2015
Primary Outcome Measure Cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and hospitalization for unstable angina
Baseline Characteristics Baseline characteristics were well balanced between the study groups
Results Per-protocol analysis:

Cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and hospitalization for unstable angina: sitagliptin 9.6%, placebo 9.6%; hazard ratio (95% CI) 0.98 (0.88-1.09), p < 0.001

Intent-to-treat analysis:

Cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and hospitalization for unstable angina: sitagliptin 11.4%, placebo 11.6%; hazard ratio (95% CI) 0.98 (0.89-1.08), p < 0.65

Adverse Events Common Adverse Events: Not reported
Serious Adverse Events: neoplasm (4.7%), gastrointestinal disorder (1.8%), musculoskeletal disorder (1.6%), respiratory (0.9%), injury/poisoning/procedural complication (2.0%)
Percentage that Discontinued due to Adverse Events: Not reported
Study Author Conclusions In our global clinical trial, which was performed in a usual-care setting among patients with type 2 diabetes and established cardiovascular disease, we found that the addition of sitagliptin to usual care among patients with glycemic equipoise did not affect rates of major atherosclerotic cardiovascular events. Sitagliptin therapy did not change rates of death from any cause, cardiovascular death, or non-cardiovascular death.

This study showed that the use of sitagliptin in patients with diabetes and cardiovascular disease did not increase the risk of cardiovascular adverse events. The study followed patients for three years; future studies should extend the duration to determine if cardiovascular risks increase if the drug is administered long term.



  • Sumrall C, Bouldin MJ.Chapter 25. Diabetes Mellitus Management. In: Linn WD, Wofford MR, O’Keefe M, Posey L.  Pharmacotherapy in Primary CareNew York, NY: McGraw-Hill; 2009.
  • Powers AC, D’Alessio D. Chapter 43. Endocrine Pancreas and Pharmacotherapy of Diabetes Mellitus and Hypoglycemia. In: Brunton LL, Chabner BA, Knollmann BC. eds. Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 12e.New York, NY: McGraw-Hill; 2011.
  • Product Information: JANUVIA(TM) oral tablets, sitagliptin oral tablets. Merck & Co,Inc, Whitehouse Station, NJ, 2007.

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