Clinical Trial Design May Skew Efficacy of Diabetes Drugs

Clinical trials study the safety and efficacy of investigational drugs in ideal conditions. Most include specific populations, while excluding individuals with comorbidities or those who have other characteristics.

Findings from a new study published by Diabetes Therapy suggest that the benefits of empagliflozin (Jardiance) are not widely applicable to the diabetes patient population.

Empagliflozin is a sodium-glucose co-transporter 2 (SGLT2) inhibitor that is indicated to improve glycemic control, in addition to diet and exercise, in patients with type 2 diabetes. The drug is also indicated to lower the risk of cardiovascular death in patients with type 2 diabetes and established heart disease.

The approval for reduction of cardiovascular death was based on a postmarketing study, which was required by the agency when Jardiance was approved in 2014. The results of the study showed that when empagliflozin was added to standard of care therapies for diabetes and atherosclerotic cardiovascular disease, it reduced the risk of cardiovascular death compared with a placebo.

An international safety trial of empagliflozin and other SGLT2 inhibitors found that the drugs have a positive effect on the cardiovascular system and can reduce the risk of heart attack. While the results were said to be groundbreaking, the trial was limited due to the focus on patients at high risk of heart disease, according to the study.

In the current study, the investigators examined data from 60,000 patients with type 2 diabetes to determine the efficacy of the drug among those at lower risk of developing cardiovascular disease.

The authors discovered that only 11% of patients with type 2 diabetes treated with empagliflozin were at high risk of cardiovascular disease. Despite the high prevalence of patients at low-to-moderate risk of heart disease, the authors found that this population may not be seeing cardiovascular improvements from the drug, according to the study.

The authors also found that only 16% of patients who were not treated with empagliflozin were at high risk of developing cardiovascular disease.

These findings suggest that clinical trials are limited as to what can be applicable to the general population and may only be beneficial for the proportion of patients included. These results often lead to misconceptions about the efficacy of a drug, according to the study.

“The benefits of this drug for patients at high risk of cardiovascular disease are clear. However, what we have found a major limitation of the clinical trial; it can only be applied to a small proportion of people with type 2 diabetes,” said lead study author Dr Andy McGovern. “Recognising [sic] this shortcoming will help clinicians better explain to patients how this drug will benefit them.”