TY - JOUR
T1 - Effects of linagliptin vs glimepiride on cognitive performance in type 2 diabetes
T2 - results of the randomised double-blind, active-controlled CAROLINA-COGNITION study
AU - Biessels, Geert Jan
AU - Verhagen, Chloë
AU - Janssen, Jolien
AU - van den Berg, Esther
AU - Wallenstein, Gudrun
AU - Zinman, Bernard
AU - Espeland, Mark A.
AU - Johansen, Odd Erik
N1 - Funding Information:
This study was sponsored by Boehringer Ingelheim. Employees of Boehringer Ingelheim were involved in the design and conduct of the study; collection, analysis, and interpretation of data; and preparation of this manuscript.
Funding Information:
Parts of these data were accepted as an abstract for the EASD Annual Meeting, 2019. The authors thank the investigators, coordinators and patients who participated in this trial. We thank A. Passera, Biostatistics and Programming Department, HMS Analytical Software, Sulzbach, Germany (at the time of the conduct of this study), for her analytical contribution, funded by Boehringer Ingelheim, and S. Abu, Biostatistics and Programming Department, Mainanalytics GmbH, Sulzbach, Germany, for analytical contribution of the revised manuscript, also funded by Boehringer Ingelheim. GJB has received research grants awarded to his institution from Boehringer Ingelheim. GW is an employee of Boehringer Ingelheim. BZ has received research grants awarded to his institution from Boehringer Ingelheim, AstraZeneca and NovoNordisk, honoraria from Janssen, Sanofi and Eli Lilly and Company, and honoraria from Boehringer Ingelheim, NovoNordisk and Merck. MAE has received honoraria from Boehringer Ingelheim. OEJ was an employee of Boehringer Ingelheim at the time of preparation of the manuscript, but is now employed by Nestlé Health Science. All other authors declare that there are no relationships or activities that might bias, or be perceived to bias, their contribution to this manuscript.
Funding Information:
GJB has received research grants awarded to his institution from Boehringer Ingelheim. GW is an employee of Boehringer Ingelheim. BZ has received research grants awarded to his institution from Boehringer Ingelheim, AstraZeneca and NovoNordisk, honoraria from Janssen, Sanofi and Eli Lilly and Company, and honoraria from Boehringer Ingelheim, NovoNordisk and Merck. MAE has received honoraria from Boehringer Ingelheim. OEJ was an employee of Boehringer Ingelheim at the time of preparation of the manuscript, but is now employed by Nestlé Health Science. All other authors declare that there are no relationships or activities that might bias, or be perceived to bias, their contribution to this manuscript.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/6
Y1 - 2021/6
N2 - Aims/hypothesis: Type 2 diabetes, particularly with concomitant CVD, is associated with an increased risk of cognitive impairment. We assessed the effect on accelerated cognitive decline (ACD) of the DPP-4 inhibitor linagliptin vs the sulfonylurea glimepiride in individuals with type 2 diabetes. Methods: The CAROLINA-COGNITION study was part of the randomised, double-blind, active-controlled CAROLINA trial that evaluated the cardiovascular safety of linagliptin vs glimepiride in individuals with age ≥40 and ≤85 years and HbA1c 48–69 mmol/mol (6.5–8.5%) receiving standard care, excluding insulin therapy. Participants were randomised 1:1 using an interactive telephone- and web-based system and treatment assignment was determined by a computer-generated random sequence with stratification by center. The primary cognitive outcome was occurrence of ACD at end of follow-up, defined as a regression-based index score ≤16th percentile on either the Mini-Mental State Examination (MMSE) or a composite measure of attention and executive functioning, in participants with a baseline MMSE score ≥24. Prespecified additional analyses included effects on ACD at week 160, in subgroups (sex, age, race, ethnicity, depressive symptoms, cardiovascular risk, duration of type 2 diabetes, albuminuria), and absolute changes in cognitive performance. Participants, caregivers, and people involved in measurements, examinations or adjudication, were all masked to treatment assignment. Results: Of 6033 participants recruited from hospital and primary care sites, 3163 (38.0% female, mean age/diabetes duration 64/7.6 years, MMSE score 28.5, HbA1c 54 mmol/mol [7.1%]) represent the CAROLINA-COGNITION cohort. Over median 6.1 years, ACD occurred in 27.8% (449/1618, linagliptin) vs 27.6% (426/1545, glimepiride), OR 1.01 (95% CI 0.86, 1.18). Also, no differences in ACD were observed at week 160 (OR 1.07 [0.91, 1.25]), between treatments across subgroups, or for absolute cognitive changes. Conclusions/interpretation: In a large, international outcome trial in people with relatively early type 2 diabetes at elevated cardiovascular risk, no difference in risk for ACD was observed between linagliptin and glimepiride over 6.1 years. Funding: This study was sponsored by Boehringer Ingelheim. Trial registration: ClinicalTrials.gov NCT01243424. Graphical abstract: [Figure not available: see fulltext.]
AB - Aims/hypothesis: Type 2 diabetes, particularly with concomitant CVD, is associated with an increased risk of cognitive impairment. We assessed the effect on accelerated cognitive decline (ACD) of the DPP-4 inhibitor linagliptin vs the sulfonylurea glimepiride in individuals with type 2 diabetes. Methods: The CAROLINA-COGNITION study was part of the randomised, double-blind, active-controlled CAROLINA trial that evaluated the cardiovascular safety of linagliptin vs glimepiride in individuals with age ≥40 and ≤85 years and HbA1c 48–69 mmol/mol (6.5–8.5%) receiving standard care, excluding insulin therapy. Participants were randomised 1:1 using an interactive telephone- and web-based system and treatment assignment was determined by a computer-generated random sequence with stratification by center. The primary cognitive outcome was occurrence of ACD at end of follow-up, defined as a regression-based index score ≤16th percentile on either the Mini-Mental State Examination (MMSE) or a composite measure of attention and executive functioning, in participants with a baseline MMSE score ≥24. Prespecified additional analyses included effects on ACD at week 160, in subgroups (sex, age, race, ethnicity, depressive symptoms, cardiovascular risk, duration of type 2 diabetes, albuminuria), and absolute changes in cognitive performance. Participants, caregivers, and people involved in measurements, examinations or adjudication, were all masked to treatment assignment. Results: Of 6033 participants recruited from hospital and primary care sites, 3163 (38.0% female, mean age/diabetes duration 64/7.6 years, MMSE score 28.5, HbA1c 54 mmol/mol [7.1%]) represent the CAROLINA-COGNITION cohort. Over median 6.1 years, ACD occurred in 27.8% (449/1618, linagliptin) vs 27.6% (426/1545, glimepiride), OR 1.01 (95% CI 0.86, 1.18). Also, no differences in ACD were observed at week 160 (OR 1.07 [0.91, 1.25]), between treatments across subgroups, or for absolute cognitive changes. Conclusions/interpretation: In a large, international outcome trial in people with relatively early type 2 diabetes at elevated cardiovascular risk, no difference in risk for ACD was observed between linagliptin and glimepiride over 6.1 years. Funding: This study was sponsored by Boehringer Ingelheim. Trial registration: ClinicalTrials.gov NCT01243424. Graphical abstract: [Figure not available: see fulltext.]
KW - Cardiovascular disease
KW - Cognitive decline
KW - DPP-4 inhibitors
KW - Sulfonylureas
KW - Type 2 diabetes
UR - http://www.scopus.com/inward/record.url?scp=85100714473&partnerID=8YFLogxK
U2 - 10.1007/s00125-021-05393-8
DO - 10.1007/s00125-021-05393-8
M3 - Article
C2 - 33559704
SN - 0012-186X
VL - 64
SP - 1235
EP - 1245
JO - Diabetologia
JF - Diabetologia
IS - 6
ER -