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T2D Patient Preference Survey Finds Low Side Effect Profile Outranks CVD Protection for Newer OADs


A drug profile matching empagliflozin, a sodium glucose cotransporter-2 (SGLT-2) inhibitor, was preferred by patients with type 2 diabetes (T2D) over profiles for the oral glucagon-like peptide-1 receptor agonist (GLP-1 RA) semaglutide and the dipetycal peptidase-4 (DPP-4) inhibitor sitagliptin in a survey designed to better understand what drug attributes may influence use.

As context for the survey investigators emphasize the focus on patient-centered care, including patient preferences regarding medication choice, which is the foundation of T2D clinical practice guidelines in the US and in Europe. Previous studies of patient preferences for OADs suggest that while glycemic and weight control are the attributes prized most, there is room for compromise that will balance efficacy with fewer side effects and convenient dosing.

Newer classes of OADs provide a range of cardiovascular (CV) and renal protective benefits that are changing the understanding of the disease of T2D and its treatment. There is little information, however, on the importance patients place on the agents’ potential CV benefits in particular compared to their side effect profile. A clear understanding of these preferences, the authors write, “is critical to the uptake of guideline-directed oral antihyperglycemic therapies.”

Researchers from the divisions of cardiology at the Karolinska Institute in Sweden and McGill University in Canada deployed a custom survey to US adults with T2D recruited from the dQ&A Diabetes Patient Panel (~15 000 people T2D and type 1 diabetes). The survey was distributed to 815 participants August 16-23, 2019.

Survey respondents were presented with hypothetical, blinded, pairwise, drug profile comparison choices, between different benefit-risk attributes and effect ranges. Benefits, harms, and other medication attributes were derived from phase 3 trials for empagliflozin 25 mg, oral semaglutide 14 mg, and sitagliptin 100 mg.


There were 553 (67.9%) surveys returned and analyzed. Approximately half (49%) of participants were aged ≥65 years and 60% were women. One-quarter of the cohort had HbA1c >8%, half (49%) fell between >7% to ≤8%. Three-quarters (76%) had BMI >30 kg/m2.

A known history of CVD was reported by 29% and 55% indicated a risk of CVD only. Slightly less than two-thirds (62%) used insulin.

The investigators found that risk of genital infection ranked as the most important perceived risk attribute, with a relative importance score of 19% (z-test, P=.077). The next most important attributes, tied statistically in second place, were fasting requirements/food restriction (15%), weight reduction (15%), risk of emesis (14%), cardiovascular benefit (12%), and risk of nausea (11%). Ranked fourth by participants, scoring 8% and 6% respectively were HbA1c reduction and the ability to coadminister an agent with other oral medications.

When blinded to drug names and dose, a significantly higher proportion of survey respondents chose the profile similar to empagliflozin (41%) compared to 31% electing the profile similar to sitagliptin and 11% the profile similar to oral semaglutide (z-test, P <0.01). The rest (17%) elected to choose none of the options.

In response to a question regarding the likelihood of taking each of the masked OAD profiles, 14% of respondents said they would “definitely” take one corresponding to empagliflozin, 13% would “definitely” take a drug with attributes similar to sitagliptin, and just 3% would “definitely” take an oral semaglutide-like OAD.

Reviewing the ranking of preferred attributes in their discussion, the research team reiterated that the greatest concern associated with the profile of an oral antihyperglycemic agent was risk of adverse events in this particular population of persons with T2D. Reduction in risk of CV death by one-third came after risk of genital infections and reduction in HbA1c was ranked last in importance, they add.

“These findings have significant implications as they suggest that patients may be hesitant to initiate guideline-directed medical oral antihyperglycemic therapies with cardiovascular benefit due to side effect concerns,” investigators wrote.

“It is possible that these findings reflect a lack of awareness amongst patients of the CV risks associated with T2DM and more focus on side effects and short-term quality of life.”

At the same time, they emphasize a role for the results in driving more in-depth shared decision making between patient and clinician, as recommended in clinical guidelines from the American Diabetes Association and its European counterparts, to support treatment adherence and improve outcomes.

Reference: Savarese G, Sharma A, Pang C, Wood R, Soleymanlou N. Patient preference for newer oral therapies in type 2 diabetes. Int J Cardiol. Published online September 10, 2022. doi:10.1016/j.ijcard.2022.09.009

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