Linagliptin poses a ‘non-inferior risk’ to cardiovascular health
Concerns about sulfonylureas’ cardiovascular safety have been put to rest after researchers unveiled new study findings which have shown linagliptin poses a “non-inferior risk” to cardiovascular health.
The ‘Effect of Linagliptin vs Glimepiride on Major Adverse Cardiovascular Outcomes in Patients With Type 2 Diabetes: The CAROLINA Randomised Clinical Trial‘ assessed cardiovascular outcomes of linagliptin vs glimepiride (sulfonylurea) in newly diagnosed people with type 2 diabetes and risk factors for or established atherosclerotic cardiovascular disease.
Rates of major adverse cardiovascular events (MACE) did not differ significantly between the sulfonylurea glimepiride (Amaryl) and the DPP-4 inhibitor linagliptin (Tradjenta) in CAROLINA.
During the median 6.3-year follow-up, 11.8% of people on linagliptin experienced MACE — a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke, versus 12% of those on glimepiride.
Fears surroundings the cardiovascular safety of sulfonylureas initially stemmed from the University Group Diabetes Program, which was conducted in the 1960s. The concerns have continued to linger until present day, despite wide global use of sulfonylureas due to their low cost.
The findings of CAROLINA were unveiled at the European Association for the Study of Diabetes (EASD) 2019 annual meeting and were simultaneously published in the journal JAMA.
Speaking at a press conference at EASD, study co-author Dr Nikolaus Marx, from the University Hospital Aachen in Germany, said: “The elevated risk that we were concerned about with sulfonylureas, this is vindicated.
More than 6,000 people with type 2 diabetes were included in the CAROLINA trial. Everyone involved either had cardiovascular risk factors or established atherosclerotic cardiovascular disease at the time of study entry.
Dr Marx added: “It’s important to note here that the participants are reflecting a patient population typically seen in clinical practice.”
Half of the participants were randomised to 5 mg of once-daily linagliptin, while the other half of the cohort received 1-4 mg of once daily glimepiride (mean dose of 2.9 mg), both therapies added to standard of care.
Among the individual MACE components, none differed significantly between treatment groups:
- CV death: HR 1.00 (95% CI 0.81-1.24, P=0.99)
- Nonfatal MI: HR 1.01 (95% CI 0.80-1.28, P=0.91)
- Nonfatal stroke: HR 0.87 (95% CI 0.66-1.15, P=0.34)
Risk for heart failure also was not significant difference between the two treatments (HR 1.21, 95% CI 0.92-1.59, P=0.18), nor was time to death by any cause (HR 0.91, 95% CI 0.78-1.06, P=0.23).
As expected, there was some weight gain with the sulfonylurea (weighted average mean difference -3.4 lb for linagliptin vs glimepiride, 95% CI -4.0 to -2.82 lb; –1.54 kg, -1.80 to –1.28 kg) — differences that also reflected some weight loss with linagliptin. However, there were no significant differences noted in regard to HbA1c, fasting plasma glucose, blood pressure, or lipid levels.
Notably, however, hypoglycaemic events were more common with the sulfonylurea. Overall, those on the DPP-4 inhibitor saw an 82% reduced risk for experiencing moderate or severe hypoglycaemia versus glimepiride (HR 0.18, 95% CI, 0.15-0.21, P<0.001). Those on the sulfonylurea not only saw an increased risk for a first hypoglycaemic event, but also for recurrent episodes.
To read the study in full, click here.