medwireNews: Cardiovascular (CV) event rates do not differ significantly among people with type 2 diabetes treated with linagliptin or glimepiride regardless of age, but those who receive linagliptin have lower risks for falls and hypoglycemia, CAROLINA trial data show.
Mark Espeland (Wake Forest School, Winston-Salem, North Carolina, USA) and co-investigators say that these latter outcomes are “particularly meaningful for older individuals.”
As previously reported by medwireNews, the primary analysis of the CAROLINA trial showed that the dipeptidyl peptidase-4 inhibitor linagliptin and the sulfonylurea glimepiride have similar CV safety profiles overall.
The current prespecified post-hoc analysis looked at outcomes by age, with the 6033 participants grouped into those younger than 65 years (50.7%), those aged 65 to 74 years (35.3%), and those aged 75 years and older (14.0%).
During approximately 6 years of follow-up, the incidence of CV death, nonfatal myocardial infarction, or nonfatal stroke (three‐point MACE) was 9.3% among the participants younger than 65 years who received linagliptin 5 mg/day and 8.4% in those who received glimepiride 1–4 mg/day.
The rates were 11.4% and 12.9%, respectively, in those aged 65 to 74 years, and 22.5% for both treatments in participants aged 75 years and older.
Espeland and team report that there were no significant differences in treatment effect for any of the age groups for three-point MACE and also for a number of other secondary and tertiary CV endpoints, including four-point MACE and in individual components of the composite outcomes.
There was also no difference between the two treatments in the reduction in glycated hemoglobin across the age groups, with weighted mean differences over 256 weeks of treatment ranging from 0.01% to 0.04%.
By contrast, the rate of moderate‐to‐severe hypoglycemia was a significant 82% lower overall with linagliptin than glimepiride, with the effect consistent across all age groups.
Specifically, the rates were 7.3% and 31.1% with linagliptin versus glimepiride in the youngest age group, 5.8% and 32.1%, respectively, in the middle age group, and 5.1% versus 27.1% in the oldest age group.
There were also significantly fewer falls or fractures with linagliptin, but only among participants aged 75 years and older, where the rates were 3.64 and 6.01 per 100 patient–years with linagliptin and glimepiride, respectively.
The investigators note that the reduced risk for falls “appeared to be associated with the lower hypoglycaemia risk with linagliptin,” and say that although this particular finding is only hypothesis-generating at present, it “may have implications for treatment choices in the elderly.”
Espeland et al conclude in Diabetes, Obesity & Metabolism that “the overall results of CAROLINA have largely dissipated the controversy about the CV safety of [sulfonylureas].”
They believe: “The current sub-analysis does the same for elderly individuals, specifically for glimepiride, which was used at a slightly lower dose than in the overall cohort.”
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