Trial Evaluating Cardiovascular Outcomes With Sitagliptin - TECOS

Aug 31, 2015
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Presenter/Author:
Frans J. J. Van de Werf, MD, FACC
Author/Summarized by Author:
Anthony A. Bavry, MD,MPH,FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Merck Sharp & Dohme
Date Presented:
08/31/2015
Date Published:
06/08/2015
Original Posted Date:
08/31/2015
References

Description:

The goal of the trial was to evaluate the dipeptidyl peptidase 4 (DPP4) inhibitor sitagliptin compared with placebo among subjects with diabetes and cardiovascular disease. Newer antihyperglycemic agents must be able to demonstrate ability to improve glycemic control without increasing adverse cardiovascular events.

Contribution to the Literature: The TECOS trial showed that sitagliptin improves glycemic control without increasing adverse cardiovascular events.

Study Design

  • Randomized
  • Parallel
  • Placebo-controlled
  • Double-blind

Subjects with diabetes and cardiovascular disease were randomized to sitagliptin 100 mg daily (n = 7,332) versus placebo (n = 7,339).

Inclusion criteria:

  • Type 2 diabetes
  • Established cardiovascular disease
  • Glycated hemoglobin level 6.5-8.0% on a stable dose of 1-2 antihyperglycemic agents or on insulin therapy

Exclusion criteria:

  • Use of a DPP4 inhibitor, glucagon-like peptide 1 (GLP1) receptor agonist, or thiazolidinedione within the last 3 months
  • History of two or more episodes of severe hypoglycemia
  • Renal insufficiency (estimated glomerular filtration rate <30 cc/min/1.73 m2)
  • Total number of enrollees: 14,735
  • Duration of follow-up: 3 years
  • Mean patient age: 65 years
  • Percentage female: 29%
  • Percentage diabetics: 100%

Principal Findings:

The primary outcome, cardiovascular death, myocardial infarction, stroke, or hospitalization for unstable angina, occurred in 11.4% of the sitagliptin group versus 11.6% of the placebo group (p for noninferiority < 0.001).

Secondary outcomes:

  • Glycated hemoglobin level: -0.29 percentage points for sitagliptin vs. placebo
  • Number of additional antihyperglycemic agents: 1,591 for sitagliptin vs. 2,046 for placebo (p < 0.001)
  • Number started on long-term insulin therapy: 542 for sitagliptin vs. 744 for placebo (p < 0.001)
  • Hospitalization for heart failure: 3.1% for sitagliptin vs. 3.1% for placebo (p = 0.98)
  • Hospitalization for heart failure (among those with history of heart failure at baseline): 7.4% for sitagliptin vs. 7.0% placebo (p = 0.86)

Interpretation:

Among diabetic subjects with documented cardiovascular disease, sitagliptin was noninferior to placebo on the outcome of adverse cardiovascular events. Of note, there was no signal for an increase in heart failure hospitalizations, which some other antihyperglycemic agents have been associated with (i.e., saxagliptin). There was also no increase in heart failure hospitalizations among those with a history of heart failure at baseline. Sitagliptin was also associated with improved glycemic control, which was characterized by a reduction in glycated hemoglobin levels and a need for fewer additional antihyperglycemic agents or long-term insulin therapy.

References:

Green JB, Bethel A, Armstrong, PW, et al., on behalf of the TECOS Study Group. Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N Engl J Med 2015;Jun 8:[Epub ahead of print].

Presented by Dr. Frans Van de Werf at the European Society of Cardiology Congress, London, August 31, 2015.

Keywords: Angina, Unstable, Blood Glucose, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Dipeptidyl-Peptidase IV Inhibitors, Double-Blind Method, Heart Failure, Glycated Hemoglobin A, Hospitalization, Hypoglycemic Agents, Insulin, Metabolic Syndrome, Primary Prevention, Stroke, ESC Congress


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