Results of new meta-analysis regarding CV events in linagliptin Phase 3 trials presented at ADA

“There is a well-established association between cardiovascular events and Type 2 Diabetes,” said Dr. Odd Erik Johansen, MD, PhD and, Senior Clinical Programme Leader, Boehringer Ingelheim. “In fact, CV events rank as the major cause of death in patients with diabetes, accounting for more than 50% of all diabetes fatalities. It is therefore important to identify treatments that do not increase the risk of CV events even further.”

The post-hoc analysis pooled results from 19 double-blind studies, included data from 9,459 patients treated with either linagliptin (5mg: 5,687, 10mg: 160) or a composite of placebo and other oral antihyperglycemic treatments (placebo: 2,675, glimepiride: 775, voglibose: 162). The cumulative patient exposure (the sum total of the length of time all patients have been exposed to either group) was 4,421 patient years in patients treated with linagliptin and 3,255 years in the composite group.

The primary endpoint of the pooled analysis was a composite of CV death, non-fatal stroke, non-fatal myocardial infarction (MI) and hospitalisation for unstable angina pectoris (UAP).

Results of the safety analysis showed fewer reported primary events in the linagliptin group versus the composite treatments (60 events in 5,847 patients vs. 62 events in 3,612 patients). This gave a lower incidence rate of 13.4 per 1,000 patient years for linagliptin compared to 18.9 per 1,000 patient years for the total comparator-treated patients as well as a lower hazard ratio of 0.78 (CI: 0.55,1.12, p = NS).¹

The long-term impact of treatment with linagliptin and glimepiride on CV morbidity and mortality is being investigated in the CAROLINA (CARdiovascular Outcome Study of LINAgliptin Versus Glimepiride in Early Type 2 Diabetes) study. CAROLINA is the only ongoing long-term cardiovascular outcome trial of a DPP-4 inhibitor versus a single active comparator (glimepiride). Announced during the ADA congress, the baseline patient characteristics for the 6,103 patient study showed that the recruited patient population is reflective of the target population with early T2D and an increased risk for CV events.² Results from the double-blind, double dummy, event driven trial are expected in 2018.

The CAROLINA patient characteristics include:²

• 33.7% of recruited patients have previous CV complications
• Diabetes duration is <5 years in 41%, 5 – 10 years in 28%
• Baseline HbA1c was 7.2% with 72.5% having HbA1c <7.5%
• 67.3% were on 1 and 22.3% were on 2 glucose-lowering agents (89.1% of patients receiving metformin)
• Population was confirmed overweight/obese with BMI <30 kg/m2 in 46% of participants

The US Food and Drug Administration (FDA), European Medicines Agency (EMA) and other regulatory authorities worldwide approved linagliptin for the treatment of adult patients with T2D as monotherapy or in combination with metformin, with metformin and a sulphonlyurea, and as add-on therapy to insulin. In the US, linagliptin is also approved for use in this population with sulphonylurea, and pioglitazone.3 With linagliptin, no dose adjustment is required regardless of declining renal function or hepatic impairment.^3,4

AboutLinagliptin

Linagliptin (5 mg, once daily) is marketed in Europe as Trajenta® (linagliptin) and in the U.S. as Tradjenta® (linagliptin), as a once-daily tablet that is used along with diet and exercise to improve glycaemic control in adults with T2D. Linagliptin should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis (increased ketones in the blood or urine).^3,4

About Diabetes

An estimated 371 million people worldwide have type 1 and T2D.⁵ T2D is the most common type, accounting for an estimated 90% of all diabetes cases.⁶ Diabetes is a chronic disease that occurs when the body either does not properly produce, or use, the hormone insulin.⁷

References

1. Johansen OE et al, Cardiovascular (CV) safety of linagliptin in patients with Type 2 Diabetes (T2D): A pooled comprehensive analysis of prospectively adjudicated CV events in Phase 3 studies. Oral Presentation No: 376-OR. Presented at the American Diabetes Association (ADA) 73rd Scientific Sessions®. June 21-25, Chicago, IL.
2. Marx N. et al,Baseline characteristics of participants enrolled in the CARdiovascular Outcome Study of LINAgliptin Versus Glimepiride in Early Type 2 Diabetes (CAROLINA). Abstract 1931. Presented at the American Diabetes Association (ADA) 73rd Scientific Sessions®. June 21-25, Chicago, IL.
3. Tradjenta® (linagliptin) tablets. Highlights of Prescribing Information. Initial US Approval: 2011.
4. EMA. Trajenta® (linagliptin) tablets. EMA Summary of Product Characteristics. 2011.
5. International Diabetes Federation. IDF Diabetes Atlas, 5th Edition: The Global Burden (2012 Update – 5th Edition).
6. Health Organization. Fact Sheet No. 312 What is Diabetes? 2009 [cited 2013 January 2013]; Available from: http://www.who.int/mediacentre/factsheets/fs312/en/index.html#
7. International Diabetes Federation. What is Diabetes? IDF Diabetes Atlas. 2011; (5th Edition)