Glucagon-like-peptide-1 receptor agonists versus dipeptidyl peptidase-4 inhibitors and cardiovascular outcomes in diabetes in relation to achieved glycemic control. A Danish nationwide study.

AIM: To compare the cardiovascular preventive effect associated with glucagon-like-peptide-1 receptor agonists (GLP-1 RA) versus dipeptidyl peptidase-4 inhibitors (DPP-4i) according to the achieved target level of glycated hemoglobin (HbA1c). METHODS: We used retrospective Danish registries to include type 2 diabetes patients already in metformin treatment initiating GLP-1 RA or DPP-4i between 2007 and 2021. Patients were included 6 months after GLP-1 RA or DPP-4i initiation. The last available HbA1c measurement before inclusion was collected. The achieved HbA1c level was categorized according to a target level below or above 53 mmol/mol (7%). The primary outcome was a composite of nonfatal myocardial infarction, nonfatal stroke, and all-cause death. We used a multivariable Cox proportional hazard model to estimate the effect of HbA1c levels on the outcome among GLP-1 RA users compared to DPP-4i users. RESULTS: The study included 13 634 GLP-1 RA users (median age 56.9, interquartile range [IQR]: 48.5-65.5; 53% males) and 39 839 DPP-4i users (median age 63.4, IQR: 54.6-71.8; 61% males). The number of GLP-1 RA and DPP-4i users according to achieved HbA1c levels were as follows: HbA1c ≤ 53 mmol/mol (≤7.0%): 3026 (22%) versus 4824 (12%); HbA1c > 53 mmol/mol (>7.0%): 6577 (48%) versus 17 508 (44%); missing HbA1c: 4031 (30%) versus 17 507 (44%). During a median follow-up of 5 years (IQR: 2.6-5.0), 954 GLP-1 RA users experienced the primary outcome compared to 7093 DPP-4i users. The 5-year risk (95% confidence interval [CI]) of the outcome associated with GLP1-RA versus DPP-4i according to HbA1c categories was as follows: HbA1c ≤ 53 mmol/mol: 10.3% (8.2-12.3) versus 24.3% (22.7-25.8); HbA1c > 53 mmol/mol: 16.0% (14.3-17.6) versus 21.1% (20.3-21.9); missing HbA1c: 17.1% (15.7-18.5) versus 25.6% (24.9-26.3). The preventive effect associated with GLP-1 RA versus DPP-4i was significantly enhanced when achieving lower HbA1c levels: HbA1c ≤ 53 mmol/mol: 0.65 (0.52-0.80); HbA1c > 53 mmol/mol: 0.92 (0.83-1.03); missing HbA1c: 0.92 (0.84-1.02) (p value for interaction <.001). CONCLUSION: GLP-1 RA use was associated with a lower rate of major adverse cardiovascular outcomes. The association was stronger in patients achieving the target glycemic level and weaker in patients not achieving the target glycemic level, suggestive of an interaction between achieved HbA1c level and GLP-1 RA.

Incidence of depression in patients with cardiovascular disease and type 2 diabetes: a nationwide cohort study.

BACKGROUND: Estimating how type 2 diabetes (T2D) affects the rate of depression in cardiovascular disease (CVD) can help identify high-risk patients. The aim is to investigate how T2D affects the rate of depression according to specific subtypes of CVD. METHODS: Incident CVD patients, free of psychiatric disease, with and without T2D, were included from nationwide registries between 2010 and 2020. We followed patients from CVD diagnosis until the first occurrence of depression, emigration, death, 5 years, or end of study (December 31, 2021). We used time-dependent Poisson regression to estimate the incidence rates and rate ratios (IRR) of depression following subtypes of CVD with and without T2D. The model included age, sex, comorbidities, calendar year, T2D duration, educational level, and living situation as covariates. RESULTS: A total of 165,096 patients were included; 45,845 had a myocardial infarction (MI), 63,691 had a stroke, 19,959 had peripheral artery disease (PAD), 35,568 had heart failure (HF), and 979 were diagnosed with 2 or more CVD subtypes (= > 2 CVD's). Baseline T2D in each CVD subtype ranged from 11 to 17%. The crude incidence rate of depression per 1000 person-years (95% confidence intervals) was: MI + T2D: 131.1 (109.6;155.6), MI: 82.1 (65.3;101.9), stroke + T2D: 287.4 (255.1;322.6), stroke: 222.4(194.1;253.6), PAD + T2D: 173.6 (148.7;201.4), PAD:137.5 (115.5;162.5), HF + T2D: 244.3 (214.6;276.9), HF: 199.2 (172.5;228.9), = > 2 CVD's + T2D: 427.7 (388.1;470.2), = > 2 CVD's: 372.1 (335.2;411.9). The adjusted IRR of depression in MI, stroke, PAD, HF, and = > 2 CVD's with T2D compared to those free of T2D was: 1.29 (1.23;1.35), 1.09 (1.06;1.12), 1.18 (1.13;1.24), 1.05 (1.02;1.09), and 1.04 (0.85;1.27) (p-value for interaction < 0.001). CONCLUSION: The presence of T2D increased the rate of depression differently among CVD subtypes, most notable in patients with MI and PAD.