Tecos Trial Design

JANUVIA® (sitagliptin) offers people aged 65 and over with T2DM the reassurance of an established renal and CV safety profile1

Many older people with T2DM may experience renal damage that can lead to increased cardiovascular risk.1 TECOS explored the safety of JANUVIA in the CV safety trial of DPP-4 inhibitors in T2DM vs. usual care alone.1

Key trial design details:

  • Randomised double blind CV safety trial1
  • Over 14,000 patients1
  • 3 years median follow up1

When added to usual care, JANUVIA demonstrated:

No increased CV risk1

Primary composite endpoint of CV death, nonfatal MI, nonfatal stroke,nonfatal myocardial infarction, or hospitalisation for unstable angina (PP HR 0.98 (95% CI: 0.88-1.09), p<0.001 for non-inferiority vs.placebo, n=14,523)1

No increased risk of hospitalisation for heart failure1
(secondary endpoint)

ITT HR 1.00 (95% CI: 0.83-1.20), p=0.985
PP: per protocol; HR: hazard ratio; CI: confidence interval;
ITT: intention-to-treat-population.

Green et al, 20151

TECOS (Trial Evaluating Cardiovascular Outcomes With Sitagliptin) is a randomised double blind controlled CV safety trial, comparing JANUVIA and placebo when added to usual care in 14,671 patients with type 2 diabetes and established cardiovascular disease. Median follow-up was 3.0 years (interquartile range, 2.3 to 3.8, maximum, 5.7).

Enrolled 14,735 patients aged >50 years with type 2 diabetes and a history of cardiovascular disease

graphic study

Both groups treated to individually appropriate HbA1c targets with the aim of no difference in the glycaemic control between arms**

•Prior antihyperglycaemic monotherapy or dual therapy† was continued after randomisation.

• Additional diabetes medications,† including insulin (excluding other DPP-4 inhibitors and GLP-1 receptor agonists), could have been added based on usual care to target individualised HbA1c goals according to local guidelines.

* Starting dose of once-daily sitagliptin was 100 mg or 50 mg for patients with eGFR 30–50 mL/min/1.73m²; if eGFR fell to <30 mL/min/1.73m², the dose was reduced to once-daily sitagliptin 25 mg; if eGFR showed sustained recovery, dose was up-titrated.

**During the study there was a small difference of HbA1c (least-square mean difference for sitagliptin vs. placebo. -0.29%; 95% confidence CI, -0.32 to -0.27, p<0.001).

† Antihyperglycaemic medication could have included metformin, sulphonylurea, pioglitazone, or insulin with or without metformin, excluding other DPP-4 inhibitors and GLP-1 RAs.

  • Januvia and Janumet should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis.
  • Use of DPP-4 inhibitors has been associated with a risk of developing acute pancreatitis. If pancreatitis is suspected, Januvia or Janumet should be discontinued; if confirmed, Januvia or Janumet should not be restarted. Caution should be exercised in patients with a history of pancreatitis. Resolution of pancreatitis has been observed after discontinuation of sitagliptin, but very rare cases of necrotising or haemorrhagic pancreatitis and/or death have been reported.
  • Hypoglycaemia has been observed when sitagliptin was used in combination with insulin or a sulphonylurea. Therefore, to reduce the risk of hypoglycaemia, a lower dose of sulphonylurea or insulin may be considered.
  • For Januvia only – Renal Impairment: Lower dosages are recommended in patients with GFR < 45 mL/min, as well as in ESRD patients requiring haemodialysis or peritoneal dialysis.
  • Janumet is contraindicated in patients with GFR < 30mL/min and should be temporarily discontinued during conditions with the potential to alter renal function.
    1. Green JB et al. N Engl J Med. 2015;373(3):232–242.