The DPP-IV inhibitor sitagliptin was safe and effective over 3 years for adults aged at least 75 years who had well-controlled type 2 diabetes and cardiovascular disease, findings from an analysis of TECOS study data show.
Limited data exist regarding safety and efficacy of antihyperglycemic drugs in older patients with type 2 diabetes. The Trial Evaluation Cardiovascular Outcomes with Sitagliptin (TECOS) was a randomized, double-blind, placebo-controlled trial assessing the impact of sitagliptin on a primary composite outcome of cardiovascular death, nonfatal stroke, nonfatal myocardial infarction, or unstable angina hospitalizations in patients with type 2 diabetes (HbA1c ≥ 6.5% [48 mmol/mol] and ≤ 8% [64 mmol/mol]) and cardiovascular disease. We analyzed baseline characteristics and clinical outcomes for TECOS participants aged ≥ 75 years.The researchers evaluated data on 14,351 adults with type 2 diabetes and CVD. Participants were divided into two groups based on age at baseline: 75 years or older (n = 2,004) or younger than 75 years (n = 12,347). Follow-up was a median 2.9 years. Participants in the older age group were randomly assigned to placebo (n = 1,034) or sitagliptin (Januvia, Merck; n = 970).
- Angelyn Bethel, MD, of the Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford in the United Kingdom, and colleagues added that, HbA1c was lower in the younger age group compared with the older age group (P < .0001). More of the older group experienced the primary composite CV outcome of CV death, nonfatal stroke, nonfatal myocardial infarction or hospitalization for unstable angina (16.9% first events; 6.46 per 100 person-years) compared with the younger group (10.4% first events; 3.67 per 100 person-years; P < .001). The risk for the secondary CV composite of CV death, nonfatal MI or nonfatal stroke (P < .001), hospitalization for heart failure (P < .001), a composite of heart failure or death (P < .001), all-cause mortality (P < .001), malignancy (P < .002), severe hypoglycemia (P = .004) and bone fractures (P < .001) was higher in the older group compared with the younger group. Pancreatitis and pancreatic cancer were uncommon, and rates were similar between the two groups.
The primary composite CV outcome occurred in 17.5% of the sitagliptin group compared with 16.2% of the placebo group (P = .39). The groups had similar rates for the secondary CV composite outcome.
The study results show that in a large group of older participants with well-controlled diabetes, sitagliptin did not increase the risk of serious hypoglycemia and was neutral with respect to CV outcomes over approximately 3 years of follow-up,” the researchers wrote. Although these results cannot exclude the possibility of other benefits or risks emerging over a longer follow-up period, especially in patients with increasingly complex comorbidities, they are reassuring for practitioners managing an aging population with diabetes.
Dr Eric Peterson (Duke Clinical Research Institute, Durham, NC), cochair of the TECOS executive committee, told the media during a press conference announcing the results. “In this study, we specifically looked at the rates of heart-failure events and found there were no differences,”. “As a matter of fact, there was no hint of heart failure seen in the sitagliptin-treated patients relative to placebo. Given the size of our study, the long duration of follow-up, as well as the higher risk of our population, we feel that this very adequately addresses and puts to bed the question that there is any risk for heart failure with this drug.”
From the results of the study it was determined that, in patients with type 2 diabetes and cardiovascular disease, the use of sitagliptin (Januvia, Merck), a dipeptidyl peptidase-4 (DPP-4) inhibitor used to lower HbA1c levels, is not associated with an increased risk of cardiovascular events, according to a large outcomes trial designed specifically to answer this question.
Most important, investigators did not observe any increase in the number of patients hospitalized for heart failure with sitagliptin, a critically watched secondary end point, given that other drugs in the class, most notably saxagliptin (Onglyza, AstraZeneca) in the SAVOR TIMI- 53 study, showed an increase in heart-failure events.
- The trial was designed to look at the risk of heart failure with the use of sitagliptin.
- TECOS was a large-scale cardiovascular-outcomes study that enrolled 14,671 patients with type 2 diabetes and established cardiovascular disease.
- There were no increase in the number of patients hospitalized for heart failure.
Green JB, Bethel MA, Armstrong PW, et al. Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N Engl J Med 2016; DOI:10.1056/NEJMoa1501352. Article