Safety of Linagliptin for Adults with Type 2 Diabetes Who Have High Risk of Cardiovascular and/or Renal Disease Examined in CARMELINA

SAN FRANCISCO, June 11, 2019 /PRNewswire/ -- Linagliptin, when added to usual diabetes care in people with type 2 diabetes (T2D) with increased risk of cardiovascular (CV) and/or renal disease, resulted in incidences of CV and renal events comparable to placebo over a median period of 2.2 years across a broad range of age and kidney function status, according to a symposium presentation today titled "Linagliptin Trial in Type 2 Diabetes Mellitus at High Cardiovascular Risk with Chronic Kidney Disease," at the American Diabetes Association's^® (ADA's) 79th Scientific Sessions^® at the Moscone Convention Center in San Francisco.

Cardiovascular disease is a major risk factor and the leading cause of death for people living with T2D. The effects of glucose-lowering therapies on cardiovascular safety and the progression of kidney disease are of importance in managing T2D, as there is an increased risk for such complications, especially in people with kidney disease or vascular complications. Whereas other studies have demonstrated CV safety of medications that are dipeptidyl peptidase 4 (DPP-4) inhibitors, there has been limited evaluation of individuals with high CV risk and chronic kidney disease.

The CARMELINA (CArdiovascular safety and Renal Microvascular outcomE with LINAgliptin in people with type 2 diabetes at high vascular risk) study aimed to determine the effect of linagliptin on the risk of major CV events, as well as the kidney safety of the medication in people with T2D, many of whom had established CV disease (57% of participants) or prevalent kidney disease (74% of participants).

"These data will better inform clinicians about the choices of glucose-lowering therapies. The results also expand the evidence-base for individuals with reduced renal function at advanced age. It was particularly reassuring that the effects were consistent in individuals that were older than 75. Typically, elderly patients are not allowed to participate, yet this is the age group in which the incidence of type 2 diabetes is increasing most rapidly," says Mark E. Cooper, AO, MB BS, PhD, FRACP, head of the diabetes department in the Central Clinical School at Monash University in Melbourne, Australia.

CARMELINA was a large, international, randomized, placebo-controlled, multicenter noninferiority trial conducted from 2013 to 2016 at 605 clinic sites in 27 countries. The study included 6,979 adults with T2D, mean age 65.9 years, with an average T2D duration of 14.8 years. Participants spanned a broad range of kidney function and this study had the highest proportion of individuals with reduced kidney function compared with other DPP-4 inhibitor cardiovascular trials to date. The participants had A1C levels of 6.5% to 10.0%, high CV risk (history of vascular disease and urine-albumin creatinine ratio [UACR] >200 mg/g) and a high renal risk (reduced eGFR and micro- or macroalbuminuria).

The study participants were randomized to receive 5 mg linagliptin once daily (n = 3494) or placebo once daily (n = 3485) added to usual care. Other glucose-lowering medications or insulin could be added based on clinical need and local clinical guidelines.

The primary outcome measure of the study was the time to first occurrence of the composite of CV events (CV death, nonfatal myocardial infarction or nonfatal stroke). The study investigators also looked at measured renal outcomes of end stage renal disease (ESRD), or sustained decrease of 40% or more in estimated glomerular filtration rate (eGFR).

The study found that participants taking linagliptin had rates of CV outcomes comparable to the participants taking the placebo, indicating linagliptin did not have a negative effect on CV risk. The results showed that linagliptin did not increase the risk of having a heart attack or stroke when compared to participants taking placebo. In the placebo group, 420 out of 3485 participants (12.1%) had a heart attack, a stroke or died due to cardiovascular disease. In the linagliptin group, 434 out of 3494 participants (12.4%) had a heart attack, stroke or died due to cardiovascular disease. There were also no differences in risk of experiencing heart failure hospitalizations or severe kidney events. The trial demonstrated that glucose control was improved with linagliptin and also that risk of worsening of albuminuria was lowered. CARMELINA confirmed that these effects were consistent across renal function groups (eGFR < 30, 30-45, 45-60 or ≥ 60 ml/min/1.73 m2) and age-groups (age < 65, 65-75 or > 75 years).

Researchers found that upon a median follow up of 2.2 years, the rates of CV events were similar in the two groups: 12.4% (434 of 3,494) in the linagliptin group and 12.1% (420 of 3,485) in the placebo group [HR 1.02 (95% CI 0.89, 1.17); p<0.001 for non-inferiority]. The key renal outcomes in the two treatment groups were also comparable: 9.4% (327 of 3494) of participants in the linagliptin group met the secondary outcomes vs. 8.8% (306 of 3485) in the placebo group [HR 1.04 (95% CI 0.89, 1.22); p=0.62].

"This data is particularly important because it proves categorically the cardiovascular and kidney safety of linagliptin in those with type 2 diabetes who are at a high cardiovascular risk when some degree of kidney disease is associated. These are patients that nearly every provider sees in his or her clinical practice on a daily basis and are difficult to treat because of risk of hypoglycemia, which was not increased with linagliptin, and these patients had better glucose control," explains lead investigator Julio Rosenstock, MD, director of the Dallas Diabetes Research Center at Medical City and clinical professor of medicine at the University of Texas Southwestern Medical Center.

To speak with Dr. Cooper or Dr. Rosenstock, please contact the ADA Press Office on-site at the Moscone Convention Center on June 7-11, by phone at 415-978-3606 or by email at [email protected].

The American Diabetes Association's 79th Scientific Sessions, the world's largest scientific meeting focused on diabetes research, prevention and care, is being held June 7-11, 2019, at the Moscone Center in San Francisco, California. Nearly 15,000 leading physicians, scientists, health care professionals and industry representatives from around the world have convened at the Scientific Sessions to unveil cutting-edge research, treatment recommendations and advances toward a cure for diabetes. During the five-day meeting, attendees receive exclusive access to more than 850 presentations and 2,000 original research presentations, participate in provocative and engaging exchanges with leading diabetes experts, and can earn Continuing Medical Education (CME) or Continuing Education (CE) credits for educational sessions. The program is grouped into eight thematic areas: Acute and Chronic Complications; Behavioral Medicine, Clinical Nutrition, Education and Exercise; Clinical Diabetes/Therapeutics; Epidemiology/Genetics; Immunology/Transplantation; Insulin Action/Molecular Metabolism; Integrated Physiology/Obesity; and Islet Biology/Insulin Secretion. Gretchen Youssef, MS, RDN, CDE, President of Health Care and Education, delivered her address, "It's All About Access!," on Saturday, June 8, and Louis H. Philipson, MD, PhD, FACP, President of Medicine and Science, delivered his lecture, "Precision Medicine—Addressing the Many Faces of Diabetes," on Sunday, June 9. Join the Scientific Sessions conversation on social media using #ADA2019.

About the American Diabetes Association
Every day more than 4,000 people are newly diagnosed with diabetes in America. Nearly 115 million Americans have diabetes or prediabetes and are striving to manage their lives while living with the disease. The American Diabetes Association (ADA) is the nation's leading voluntary health organization fighting to bend the curve on the diabetes epidemic and help people living with diabetes thrive. For nearly 80 years the ADA has been driving discovery and research to treat, manage and prevent diabetes, while working relentlessly for a cure. We help people with diabetes thrive by fighting for their rights and developing programs, advocacy and education designed to improve their quality of life. Diabetes has brought us together. What we do next will make us Connected for Life. To learn more or to get involved, visit us at diabetes.org or call 1-800-DIABETES (1-800-342-2383). Information is available in English and Spanish. Join the fight with us on Facebook (American Diabetes Association), Twitter (@AmDiabetesAssn) and Instagram (@AmDiabetesAssn).

Press Office in San Francisco
June 7-11, 2019
415-978-3606

Contact:
Michelle Kirkwood
(703) 299-2053
[email protected]

SOURCE American Diabetes Association

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