Linagliptin CV Safety; Insulin Storage; Renal Outcomes

BERLIN -- Novel and updated treatment strategies for managing type 2 diabetes were at the forefront of European Association for the Study of Diabetes (EASD) annual meeting.

Some of the new research that was presented included a novel GIP/GLP-1 receptor agonist, cardiovascular outcomes from the GLP-1 RA albiglutide, and blood glucose benefits from the weight loss drug lorcaserin (Belviq). Below are a few more of the research highlights from the 2018 meeting.

CARMELINA

The DPP-4 inhibitor linagliptin (Trajenta) was safe for long-term cardiovascular and renal health, according to results of the multicenter Cardiovascular and Renal Microvascular Outcome Study with Linagliptin in Patients with Type 2 Diabetes Mellitus trial. In the trial of nearly 7,000 adults with type 2 diabetes, 5 mg of once-daily linagliptin plus standard care exhibited a non-inferiority for cardiovascular safety compared with placebo over a median 2.2-year follow-up period, meeting the trial's primary endpoint of time to first occurrence of the composite outcomes of cardiovascular death, non-fatal MI, or non-fatal stroke.

Among one of the secondary endpoints, the treatment also showed non-inferiority to placebo for renal safety. There was also a similar rate of hospitalization due to heart failure among patients on linagliptin compared with placebo (12.4% vs 12.1%), which was a prespecified tertiary endpoint.

"If confirmed by the FDA, this might have implications for the heart failure warning that the FDA has imposed on the entire class currently," commented Sanjay Kaul, MD, of Cedars-Sinai Medical Center in Los Angeles, to MedPage Today. Kaul was not involved in the trial.

Another cardiovascular outcomes trial assessing linagliptin (CAROLINA) is expected in the future, according to CARMELINA funders Boehringer Ingelheim and Eli Lilly. CAROLINA will compare linagliptin to glimepiride (Amaryl), another commonly prescribed second-line diabetes treatment.

Refrigerating Insulin

Many patients may be storing their insulin in unsafe temperature, according to Katarina Braune, MD, of Charité-Universitaetsmedizin Berlin in Germany, and colleagues. Using temperature loggers placed either in a refrigerator or diabetes bag, insulin placed in domestic refrigerators was out of ideal temperature storage range more often than in carriers.

Specifically, refrigerated insulin was out of the ideal range of 35.6-46.6°F (2-8°C) over 11% (10.10-13.10%) of the time -- equal to around 2 hours and 43 min per day out of range -- while carried insulin was out of the range of 35.6-86°F (2-30°C) 0.54% (0.48-0.64%) of the time -- only about 8 minutes per day.

The researchers stated in a poster presentation that "domestic refrigerators may pose an underestimated risk for insulin quality. The extent of how temperature deviations in storage affect insulin efficacy and patient outcomes needs further systematic investigation."

ELIXA Renal Outcomes

Lixisenatide (Adlyxin), a short-acting GLP-1 receptor agonist, reduced progression in urinary albumin-to-creatinine ratio in patients with macroalbuminuria (least-squares mean percentage change from baseline: -39.18%, 95% CI -68.53 to -9.84, P=0.0070). Once-daily, injectable lixisenatide treatment of 10 to 20 μg in additional to usual care was linked to a reduced risk of new macroalbuminuria compared with placebo (adjusted for baseline HbA1c, HR 0.808, 95% CI 0.660-0.991, P=0.0404).

Marcel Muskiet, MD, of University Medical Center in Amsterdam, and colleagues shared results of the 108-week exploratory analysis of the previously reported ELIXA trial. It included data on over 6,000 adult participants with type 2 diabetes and a recent coronary artery event. Results were simultaneously published in the Lancet.

"This effect holds promise for patients with type 2 diabetes and diabetic kidney disease, as we're currently seeing that the current algorithm that we're using in these patients is very limited and we do need new treatment strategies," Muskiet said at an EASD press conference.

EASD/ADA Consensus Report

The EASD and the American Diabetes Association (ADA) updated 2012 and 2015 consensus statements and recommendations in regards to best treatments for managing type 2 diabetes.

The consensus report in Diabetologia renewed focus on lifestyle modification. EASD and ADA now recommend patients with type 2 diabetes and comorbid obesity focus on weight loss interventions, including lifestyle, pharmacological, and surgical procedures, such as metabolic surgery. As for patients with comorbid cardiovascular disease, the consensus report recommended adding either an SGLT-2 inhibitor or GLP-1 RA to the treatment regimen.

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