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Effect of Linagliptin on Cognitive Performance in Patients With Type 2 Diabetes and Cardiorenal Comorbidities: The CARMELINA Randomized Trial
Biessels GJ, Verhagen C, Janssen J, van den Berg E, Zinman B, Rosenstock J, George JT, Passera A et al.. Diabetes care, 2019-08-09
Topic: Drug trials: efficacy and safety
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 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 m 2 ; and HbA 1c , 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.
Key findings
- Objective Type 2 diabetes is associated with cognitive dysfunction and an increased dementia risk, particularly in individuals with concomitant cardiovascular and/or kidney disease.
- 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 m 2 ; and HbA 1c , 7.8 ± 0.9% [61.4 ± 10.1 mmol/mol]).
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Study details
- Participants1,545
- Effect size0.9%; 28.4%; 29.3%
- Evidence strengthHigh
How this study scored 83/100
Published in a leading specialty journal, and it is a randomised controlled trial. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 48 of the 58 points we could judge it on, which is 83 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Diabetes care) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 11 / 12 | A randomised controlled trial (from PubMed type “Randomized Controlled Trial”) |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2019 — within 10 year(s) of the newest study here |
| Sample size | 3 / 4 | 1,545 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 1 / 2 | Randomised (as stated in the record) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 31399442) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 48 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 48 of the 58 points we could judge it on is 83 out of 100. |
| Total | 83 / 100 | — |
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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APA 7th
Biessels, G. J., Verhagen, C., Janssen, J., van den Berg, E., Zinman, B., Rosenstock, J., et al. (2019). Effect of Linagliptin on Cognitive Performance in Patients With Type 2 Diabetes and Cardiorenal Comorbidities: The CARMELINA Randomized Trial. Diabetes care. https://doi.org/10.2337/dc19-0783
Vancouver
Biessels GJ, Verhagen C, Janssen J, van den Berg E, Zinman B, Rosenstock J, et al. Effect of Linagliptin on Cognitive Performance in Patients With Type 2 Diabetes and Cardiorenal Comorbidities: The CARMELINA Randomized Trial. Diabetes care. 2019. doi:10.2337/dc19-0783. PMID: 31399442.
BibTeX
@article{biessels2019-31399442,
author = {Biessels, G. J. and Verhagen, C. and Janssen, J. and van den Berg, E. and Zinman, B. and Rosenstock, J. and George, J. T. and Passera, A. and others},
title = {{Effect of Linagliptin on Cognitive Performance in Patients With Type 2 Diabetes and Cardiorenal Comorbidities: The CARMELINA Randomized Trial}},
journal = {Diabetes care},
year = {2019},
doi = {10.2337/dc19-0783},
pmid = {31399442},
url = {https://doi.org/10.2337/dc19-0783}
}
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