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Diabetes Care. 2019 Aug 9. pii: dc190783. doi: 10.2337/dc19-0783. [Epub ahead of print]

Effect of Linagliptin on Cognitive Performance in Patients With Type 2 Diabetes and Cardiorenal Comorbidities: The CARMELINA Randomized Trial.

Author information

1
Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, the Netherlands g.j.biessels@umcutrecht.nl.
2
Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, the Netherlands.
3
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.
4
Department of Neurology, Erasmus MC-University Medical Center, Rotterdam, the Netherlands.
5
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
6
Dallas Diabetes Research Center, Dallas, TX.
7
Therapeutic Area Cardiometabolism, Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
8
HMS Analytical Software GmbH, Sulzbach, Germany.
9
Biostatistics and Data Sciences, Boehringer Ingelheim, Biberach, Germany.

Abstract

OBJECTIVE:

Type 2 diabetes is associated with cognitive dysfunction and an increased dementia risk, particularly in individuals with concomitant cardiovascular and/or kidney disease. Incretin therapies may modulate this risk via glycemic and nonglycemic pathways. We explored if the dipeptidyl peptidase 4 inhibitor linagliptin could prevent cognitive decline in people with type 2 diabetes with cardiorenal disease.

RESEARCH DESIGN AND METHODS:

The CArdiovascular and Renal Microvascular outcomE study with LINAgliptin (CARMELINA)-COG substudy was an integral part of CARMELINA (NCT01897532) that randomized participants with cardiorenal disease to linagliptin 5 mg or placebo once daily (1:1), in addition to standard of care. The primary cognitive outcome was the occurrence of accelerated cognitive decline at the end of treatment, defined as a regression-based index score ≤16th percentile on the Mini-Mental State Examination (MMSE) or a composite measure of attention and executive functioning and was analyzed in participants with a baseline MMSE ≥24. Effects across subgroups by baseline factors, as well as absolute cognitive changes, were also assessed.

RESULTS:

Of the 6,979 participants in CARMELINA, CARMELINA-COG included 1,545 (mean ± SD age, 68 ± 8 years; MMSE, 28.3 ± 1.7; estimated glomerular filtration rate, 52 ± 23 mL/min/1.73 m2; and HbA1c, 7.8 ± 0.9% [61.4 ± 10.1 mmol/mol]). Over a median treatment duration of 2.5 years, accelerated cognitive decline occurred in 28.4% (linagliptin) vs. 29.3% (placebo) (odds ratio 0.96 [95% CI 0.77, 1.19]). Consistent effects were observed across subgroups by baseline characteristics. Absolute cognitive performance changes were also similar between treatment groups.

CONCLUSIONS:

In a large, international cardiovascular outcome trial in people with type 2 diabetes and cardiorenal disease, linagliptin did not modulate cognitive decline over 2.5 years.

PMID:
31399442
DOI:
10.2337/dc19-0783

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