DPP4 inhibitor is safe in older diabetic participants
Assessing the Safety of Sitagliptin in Older Participants in the Trial Evaluating Cardiovascular Outcomes With Sitagliptin (TECOS)
Diabetic patients ≥75 years suffer more often from kidney dysfunction, heart failure (HF), and cardiovascular disease (CVD), making therapeutic decisions more complex . Moreover, clinical data from patients with type 2 diabetes mellitus (T2DM) who are ≥75 years, are scarce . In the TECOS trial, the cardiovascular (CV) safety of the DPP4 inhibitor sitagliptin versus placebo on top of standard care was assessed in T2DM patients with CVD .
In this analysis of the TECOS trial, baseline characteristics, clinical outcomes and the safety profile for sitagliptin in participants ≥75 years, are described. First these were compared between older and younger participants, than these were compared within the older cohort between sitagliptin and placebo-treated participants.
- Out of 14,351 randomised TECOS participants with an age recorded, 14% were ≥75 years old, and 4% were ≥80 years old.
- The median study drug exposure was shorter in the older compared with younger participants: 2.4 years (IQR 1.7-3.2) vs. 2.7 years (IQR 2.0-3.5), and more of the older participants discontinued the study drug during follow-up (36.6% vs. 24.1%).
- Statistical differences were seen between older and younger cohorts for all baseline characteristics except for gender and administration of some medications (sulfonylurea, insulin, statin, and other lipid-lowering therapies).
- The primary composite CV outcome (CV death, non-fatal stroke, non-fatal myocardial infarction (MI) or hospitalisation for unstable angina) occurred more often in the older cohort: 16.9%, corresponding to 6.46 per 100 person-years compared with 10.4%, corresponding to 3.67 per 100 person-years (HR 1.72, 95% CI: 1.52–1.94, P<0.001).
- Older participants were at higher risk for the secondary CV composite endpoint CV death, non-fatal MI, or non-fatal stroke (HR 1.86, 95% CI: 1.63–2.11, P<0.001), HF hospitalisation (HR 1.48, 95% CI: 1.18–1.87, P<0.001), a composite of HF or death (HR 2.02, 95% CI: 1.75-2.34, P<0.001), all-cause mortality (HR 2.52, 95% CI: 2.20–2.89, P<0.001), malignancy (HR 1.76, 95% CI: 1.43–2.15, P<0.001), severe hypoglycaemia (HR 1.53, 95% CI: 1.15–2.03, P=0.004) and bone fractures (HR 1.84, 95% CI: 1.44–2.35, P<0.001).
- The most common system organ class serious adverse event reported in the older cohort was “neoplasms benign, malignant and unspecified” in 174 individuals vs. 527 in the younger cohort (difference in proportion with event 4.49%, 95% CI: 3.26–5.86).
- After 4 months of study treatment, the mean hemoglobulin A1c (HbA1c) values were 0.4 percentage points lower in the older participants receiving sitagliptin.
- In the intention-to-treat population, the primary composite CV endpoint occurred in 17.5% of participants in the sitagliptin group, corresponding to 6.75 per 100 person-years, and in 16.2% of participants in the placebo group, corresponding to 6.19 per 100 person-years (HR 1.10, 95% CI: 0.89–1.36, P=0.39)
- No differences were seen between treatment groups for the secondary CV composite of CV death, nonfatal MI or nonfatal stroke (HR 1.01, 95% CI 0.81-1.26, P=0.94), hospitalization for heart failure (HR 0.99, 95% CI 0.65-1.49, P=0.94), a composite of heart failure or death (HR 1.00, 95% CI 0.77-1.29, P=0.99), all-cause mortality (HR 1.05, 95% CI 0.83-1.32, P=0.71), malignancy (HR 0.95, 95% CI 0.67-1.36, P=0.78), severe hypoglycemia (HR 1.03, 95% CI 0.62-1.71, P=0.92) and bone fractures (HR 1.21, 95% CI 0.78-1.85, P=0.40).
- Number of serious adverse events were small and generally well balanced between treatment groups.
In a large group of participants ≥75 years with well-controlled diabetes, sitagliptin did not increase the risk of serious hypoglycaemia and was neutral with respect to CV outcomes during 3 years of follow-up. These results contribute to better decision making, when it comes to the treatment of older diabetic patients in clinical practice.