CARMELINA® subgroup analysis supports long-term cardiovascular and renal safety of linagliptin in older people with type 2 diabetes 

Ingelheim, Germany, 12 February 2020 – Boehringer Ingelheim have announced the results of a subgroup analysis of the CARMELINA^® trial which demonstrate that linagliptin did not increase the risk of adverse cardiovascular events or hypoglycemia compared with placebo in older people with type 2 diabetes.¹ The findings have been published in the Diabetes Obesity and Metabolism journal.

Population aging has shifted the epidemiology of diabetes towards older age.¹ Currently, approximately 136 million of the estimated 463 million people with diabetes are aged over 65 years.² However, despite the high prevalence, older patients have historically been underrepresented in clinical trials of glucose-lowering drugs.³

The recent CARMELINA^® cardiovascular outcome trial enrolled people aged 18 years and older with no maximum age restriction.⁴ The prespecified CARMELINA^® subgroup analysis evaluated clinical outcomes and adverse events with the main findings grouped into the following predefined age categories: <65, 65 to <75, and ≥75 years.¹ 

“This subset analysis shines a spotlight on the older population living with type 2 diabetes. These individuals can be frail, have a high rate of comorbidities and can be on multidrug regimens, all of which present a challenge for their glucose management,” said Waheed Jamal, MD, Corporate Vice President and Head of CardioMetabolic Medicine, Boehringer Ingelheim. “As the older population also has the highest incidence of type 2 diabetes of any age group, this analysis will be invaluable in helping clinicians manage the treatment of this patient group, previously underrepresented in clinical studies.”

Linagliptin did not increase the risk of adverse kidney outcomes, cardiovascular events or hospitalization for heart failure compared with placebo across age groups.¹ The incidence of adverse events, including hypoglycemia, increased with age but was similar with linagliptin and placebo despite HbA_1c reduction with linagliptin.¹ Linagliptin improved glycemic control compared with placebo in all age groups.¹ 

“Their advanced age, combined with established cardiovascular and/or kidney disease, means the older population of CARMELINA^® was comprised of high-risk individuals with type 2 diabetes,” continued Dr. Jamal. “The results should reassure healthcare professionals that linagliptin is suitable for a wide patient population to improve glycemic control whilst ensuring cardiovascular and renal safety.”

About CARMELINA^®
CARMELINA^® is a multi-national, randomized, double-blind, placebo-controlled clinical trial that involved 6,979 adults with type 2 diabetes from 27 countries at more than 600 sites observed for a median duration of 2.2 years.^4,5 The study was designed to assess the effect of linagliptin (5mg once daily) compared to placebo (both added to standard of care) on cardiovascular outcomes in adults with type 2 diabetes and high cardiovascular risk, the majority of whom also had kidney disease.^4,5 This population of people with high risk of cardiovascular and/or kidney disease reflects patients that doctors see in their daily practice.⁶ Standard of care included both glucose lowering agents and cardiovascular drugs (including antihypertensive and lipid lowering agents). 

CARMELINA^® was led by an academic trial steering committee and the Boehringer Ingelheim and Eli Lilly and Company Diabetes Alliance. Compared to other recently reported outcome trials of dipeptidyl peptidase-4 (DPP-4) inhibitors in type 2 diabetes, CARMELINA^® included the highest proportion of patients with impaired kidney function.^7*

To learn more about CARMELINA^®, please visit: https://www.carmelinatrial.com/     
 

About Trajenta^® (linagliptin)
Trajenta^® is a one dose, once daily DPP-4 inhibitor that provides significant efficacy in the reduction of blood sugar levels for adults with type 2 diabetes. It can be prescribed for adults with type 2 diabetes regardless of age, disease duration, ethnicity, body mass index (BMI), liver and kidney function.⁸ Trajenta^® has the lowest kidney excretion rate of all globally available DPP-4 inhibitors.^9–12 

Linagliptin is developed and commercialized by the Boehringer Ingelheim and Eli Lilly and Company Alliance.
 

About our cardiovascular outcome trials
Cardiovascular outcome trials are highly clinically relevant, as cardiovascular disease is a major complication and the leading cause of death in type 2 diabetes. Worldwide, most people with type 2 diabetes die of a cardiovascular event.¹³ In 2015, Boehringer Ingelheim and Eli Lilly and Company announced results from the landmark cardiovascular outcome trial EMPA-REG OUTCOME^® with the SGLT2 inhibitor, empagliflozin, which reduced the relative risk of cardiovascular death by 38 percent in adults with type 2 diabetes and established cardiovascular disease, on top of standard of care.^{†‡14–16} As a result, empagliflozin was the first oral type 2 diabetes medicine to have either a cardiovascular indication or data on the reduction of the risk of cardiovascular death included in the label in many countries.^14,15

CAROLINA^® is one of two cardiovascular outcome trials with the DPP-4 inhibitor, linagliptin.^17,18 CAROLINA^® and the CArdiovascular safety and Renal Microvascular outcomE with LINAgliptin in patients with type 2 diabetes at high vascular risk trial (CARMELINA^®)^4,5 provide one of the most comprehensive datasets on the long-term safety of a DPP-4 inhibitor.

CARMELINA^® is a multi-national, randomized, double-blind, placebo-controlled clinical trial that involved 6,979 adults with type 2 diabetes from 27 countries at more than 600 sites observed for a median duration of 2.2 years^.4,5 CARMELINA^® studied the impact of Trajenta^® (linagliptin) on cardiovascular and kidney safety in adults with type 2 diabetes at high risk for heart and/or kidney disease.^4,5 The trial met its primary endpoint,^§ with linagliptin demonstrating a similar cardiovascular safety profile compared to placebo when added to standard of care.⁵ CARMELINA^® also included a key secondary composite endpoint,^** showing a similar kidney safety profile compared to placebo.⁵ The overall safety profile of linagliptin in CARMELINA^® was consistent with previous data and no new safety signals were observed.^5,6 CARMELINA^® also showed a similar rate of hospitalization for heart failure for linagliptin compared to placebo.⁵ 

To learn more about CAROLINA^® and CARMELINA^®, please visit: https://www.carmelinatrial.com/.  
 

About Boehringer Ingelheim 
Improving the health of humans and animals is the goal of the research-driven pharmaceutical company Boehringer Ingelheim. The focus in doing so is on diseases for which no satisfactory treatment option exists to date. The company therefore concentrates on developing innovative therapies that can extend patients’ lives. In animal health, Boehringer Ingelheim stands for advanced prevention. 

Family-owned since it was established in 1885, Boehringer Ingelheim is one of the pharmaceutical industry’s top 20 companies. Some 50,000 employees create value through innovation daily for the three business areas: human pharmaceuticals, animal health and biopharmaceuticals. In 2018, Boehringer Ingelheim achieved net sales of around 17.5 billion euros. R&D expenditure of almost 3.2 billion euros, corresponded to 18.1 percent of net sales. 

As a family-owned company, Boehringer Ingelheim plans in generations and focuses on long-term success. The company therefore aims at organic growth from its own resources with simultaneous openness to partnerships and strategic alliances in research. In everything it does, Boehringer Ingelheim naturally adopts responsibility towards mankind and the environment. 

More information about Boehringer Ingelheim can be found on www.boehringer-ingelheim.com or in our annual report: https://annualreport.boehringer-ingelheim.com.

Intended audiences
This press release is issued from Boehringer Ingelheim Corporate Headquarters in Ingelheim, Germany and is intended to provide information about our global business. Please be aware that information relating to the approval status and labels of approved products may vary from country to country, and a country-specific press release on this topic may have been issued in the countries where Boehringer Ingelheim and Eli Lilly and Company do business.

Footnotes

^*   Glomerular filtration rate below 60 mL/min/1.73m2
^†   Adult patients with type 2 diabetes and coronary artery disease, peripheral artery disease or a history of MI or stroke
^‡   Standard of care included cardiovascular medications and blood sugar lowering agents given at the discretion of physicians
^§   Primary endpoint defined as time to first occurrence of the 3P-MACE (cardiovascular death, non-fatal myocardial infarction or non-fatal stroke)
^** Key secondary endpoint defined as time to first occurrence of sustained end stage kidney disease (ESKD), death due to kidney disease, or a sustained decrease in eGFR from baseline of ≥40 percent compared to placebo

References

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2. IDF Diabetes Atlas, 9th edition. Brussels, Belgium: International Diabetes Federation; 2019. Available at: www.diabetesatlas.org/. Accessed: January 2020.
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6. Boehringer Ingelheim and Eli Lilly and Company. Data on file.
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