scholarly journals Effects of canagliflozin compared with placebo on major adverse cardiovascular and kidney events in patient groups with different baseline levels of HbA1c, disease duration and treatment intensity: results from the CANVAS Program

Diabetologia ◽  
2021 ◽  
Author(s):  
Tamara K. Young ◽  
Jing-Wei Li ◽  
Amy Kang ◽  
Hiddo J. L. Heerspink ◽  
Carinna Hockham ◽  
...  

Abstract Aims/hypothesis Type 2 diabetes mellitus can manifest over a broad clinical range, although there is no clear consensus on the categorisation of disease complexity. We assessed the effects of canagliflozin, compared with placebo, on cardiovascular and kidney outcomes in the CANagliflozin cardioVascular Assessment Study (CANVAS) Program over a range of type 2 diabetes mellitus complexity, defined separately by baseline intensity of treatment, duration of diabetes and glycaemic control. Methods We performed a post hoc analysis of the effects of canagliflozin on major adverse cardiovascular events (MACE) according to baseline glucose-lowering treatments (0 or 1, 2 or 3+ non-insulin glucose-lowering treatments, or insulin-based treatment), duration of diabetes (<10, 10 to 16, >16 years) and HbA1c (≤53.0 mmol/mol [<7.0%], >53.0 to 58.5 mmol/mol [>7.0% to 7.5%], >58.5 to 63.9 mmol/mol [>7.5 to 8.0%], >63.9 to 69.4 mmol/mol [8.0% to 8.5%], >69.4 to 74.9 mmol/mol [>8.5 to 9.0%] or >74.9 mmol/mol [>9.0%]). We analysed additional secondary endpoints for cardiovascular and kidney outcomes, including a combined kidney outcome of sustained 40% decline in eGFR, end-stage kidney disease or death due to kidney disease. We used Cox regression analyses and compared the constancy of HRs across subgroups by fitting an interaction term (p value for significance <0.05). Results At study initiation, 5095 (50%) CANVAS Program participants were treated with insulin, 2100 (21%) had an HbA1c > 74.9 mmol/mol (9.0%) and the median duration of diabetes was 12.6 years (interquartile interval 8.0–18 years). Canagliflozin reduced MACE (HR 0.86 [95% CI 0.75, 0.97]) with no evidence that the benefit differed between subgroups defined by the number of glucose-lowering treatments, the duration of diabetes or baseline HbA1c (all p-heterogeneity >0.17). Canagliflozin reduced MACE in participants receiving insulin with no evidence that the benefit differed from other participants in the trial (HR 0.85 [95% CI 0.72, 1.00]). Similar results were observed for other cardiovascular outcomes and for the combined kidney outcome (HR for combined kidney outcome 0.60 [95% CI 0.47, 0.77]), with all p-heterogeneity >0.37. Conclusions/interpretation In people with type 2 diabetes mellitus at high cardiovascular risk, there was no evidence that cardiovascular and renal protection with canagliflozin differed across subgroups defined by baseline treatment intensity, duration of diabetes or HbA1c. Graphical abstract

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Tamara Young ◽  
Jing-wei Li ◽  
Amy Kang ◽  
Hiddo Heerspink ◽  
Carinna Hockham ◽  
...  

Abstract Background and Aims Patient with type 2 diabetes mellitus (T2DM) included in trials of sodium-glucose cotransporter 2 inhibitors are heterogeneous in terms of disease severity. We assessed the effects of canagliflozin compared to placebo on cardiovascular and renal outcomes in the CANVAS program according to severity of T2DM as indicated by intensity of treatment, duration of diabetes and glycaemic control. Method We compared effects on major adverse cardiovascular events ([MACE], defined as cardiovascular death, non-fatal myocardial infarction or non-fatal stroke) according to three indicators of T2DM severity at study baseline: number of oral glucose lowering treatments or insulin therapy (0-1, 2, 3+, insulin), duration of diabetes (&lt;10, 10-16, &gt;16 years) and HbA1c (&lt;7.0, 7.0-7.5, 7.5-8.0, 8.0-8.5, 8.5-9, &gt;9.0%). We also assessed effects on other pre-specified cardiovascular outcomes, and an adjudicated composite of end-stage kidney disease, renal death or sustained 40% decline in estimated glomerular filtration rate. We assessed for constancy of hazard ratios across subgroups by fitting an interaction term that tested for linear trend. Results Of 10,142 participants in the CANVAS Program, 1011 experienced a MACE during a mean follow-up of 3.6 years. Event rates for MACE were higher in those with longer duration of diabetes and higher HbA1c at baseline. The effect of canagliflozin on MACE in the overall population (HR 0.86, 95 % CI 0.75-0.97) was consistent irrespective of the number of glucose lowering treatments (p=0.509), duration of diabetes (p=0.174) and baseline HbA1c (p =0.314). Effects were also consistent across different levels of T2DM disease severity for all other outcomes studied. Conclusion Higher event rates were observed in those with longer disease duration and higher HbA1c. The proportional risk reductions achieved with canagliflozin were comparable regardless of diabetes duration, number of therapies or HbA1C at baseline.


2017 ◽  
Vol 11 (1) ◽  
pp. 19-24 ◽  
Author(s):  
Muhammad Abdur Rahim ◽  
Palash Mitra ◽  
Hasna Fahmima Haque ◽  
Tasrina Shamnaz Samdani ◽  
Shahana Zaman ◽  
...  

Background and objectives: Diabetes mellitus is one of the most common causes of chronic kidney disease (CKD). The prevalence of CKD in type 2 diabetes mellitus (T2DM) in Bangladesh is not well described. The present study aimed to find out the prevalence of CKD stages 3-5 and its risk factors among selected Bangladeshi T2DM patients.Methods: This cross-sectional study was conducted in BIRDEM (Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders) General Hospital, Dhaka, Bangladesh from July to December 2015. Diagnosed adult T2DM patients were consecutively and purposively included in this study. Pregnant women, patients with diagnosed kidney disease due to non-diabetic etiology, acute kidney injury (AKI), AKI on CKD and patients on renal replacement therapy were excluded. Age, gender, body mass index (BMI) and laboratory parameters were recorded systematically in a predesigned data sheet. Diagnosis of CKD and its stages were determined according to Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guidelines 2012 and estimated glomerular filtration rate (eGFR). Estimated GFR was calculated by using Modification of Diet in Renal Disease (MDRD), Cockcroft-Gault (CG) and Chronic Kidney Disease Epidemiology (CKDEPI) creatinine based formula.Results: A total of 400 patients with T2DM of various durations were enrolled in the study. Out of 400 patients, 254 (63.5%), 259 (64.75%) and 218 (54.5%) cases had CKD stages 3-5 according to MDRD, C-G and CKD-EPI equations respectively. CKD was significantly more common in females (p<0.001) and in cases with long duration of diabetes (?5 years; p=0.007). CKD stages 3-5 were significantly associated with hypertension (?2=5.2125, p =0.02) and good control of diabetes (HbA1c <7%) as evidenced by higher proportion of CKD in them (73.3%) compared to those with poor glycemic control (52.1%).Conclusions: More than half of T2DM patients had CKD stages 3-5. Female gender, duration of diabetes and hypertension were significant risk factors and should be emphasized for the prevention of CKD in T2DM. Glycemic control may not reduce CKD in diabetes.IMC J Med Sci 2017; 11(1): 19-24


Author(s):  
Sajith Kumar Soman ◽  
Binu Areekal ◽  
Rosin George Varghese ◽  
Susan John ◽  
Radhika S. Gopan ◽  
...  

Background: Diabetes mellitus (DM) is one of the most common metabolic diseases characterized by increased blood glucose levels either due to insufficiency/absence of insulin or due to decrease in the insulin sensitivity. The prevalence of chronic kidney disease (CKD) in people with type 2 diabetes is three times higher than in non-diabetic population and majority of people developing end-stage renal diseases (ESRD) have Type 2 DM. The objectives of the study were to find out the prevalence of CKD, mean GFR and associated factors of CKD, in diabetics coming to a primary health care setting in Central Kerala.Methods: A cross-sectional study among all patients attending the NCD clinic of Health Centre, Ettumanoor with confirmed diagnosis of type 2 diabetes mellitus was done between February 2017 and April 2017.Results: The prevalence of CKD among the study population was 45.3%. The proportion of CKD was 34.9% among those with nil urinary protein, 57.1% among those with 1+ urinary protein, 88.9% for those with 2+ and 87.5% among those with 3+ urinary protein. Among those with CKD mean duration of diabetes was 121.92 months against 92.72 months among those without CKD. There was statistically significant difference between RBS values of those with CKD and without CKD (238.49 mg% versus 199.41 mg%). The proportion of CKD was found increase with duration of diabetes 5 years (31.2%), 5-10 years (47.8%), 10-15 years (52.6%) and >15 years (55%).Conclusions: The study showed high prevalence of CKD among diabetics. The duration of diabetes, urinary protein levels and RBS value were found to have strong association with CKD in diabetics.


Diabetologia ◽  
2021 ◽  
Author(s):  
David Z. I. Cherney ◽  
◽  
Bernard Charbonnel ◽  
Francesco Cosentino ◽  
Samuel Dagogo-Jack ◽  
...  

Abstract Aims/hypothesis In previous work, we reported the HR for the risk (95% CI) of the secondary kidney composite endpoint (time to first event of doubling of serum creatinine from baseline, renal dialysis/transplant or renal death) with ertugliflozin compared with placebo as 0.81 (0.63, 1.04). The effect of ertugliflozin on exploratory kidney-related outcomes was evaluated using data from the eValuation of ERTugliflozin effIcacy and Safety CardioVascular outcomes (VERTIS CV) trial (NCT01986881). Methods Individuals with type 2 diabetes mellitus and established atherosclerotic CVD were randomised to receive ertugliflozin 5 mg or 15 mg (observations from both doses were pooled), or matching placebo, added on to existing treatment. The kidney composite outcome in VERTIS CV (reported previously) was time to first event of doubling of serum creatinine from baseline, renal dialysis/transplant or renal death. The pre-specified exploratory composite outcome replaced doubling of serum creatinine with sustained 40% decrease from baseline in eGFR. In addition, the impact of ertugliflozin on urinary albumin/creatinine ratio (UACR) and eGFR over time was assessed. Results A total of 8246 individuals were randomised and followed for a mean of 3.5 years. The exploratory kidney composite outcome of sustained 40% reduction from baseline in eGFR, chronic kidney dialysis/transplant or renal death occurred at a lower event rate (events per 1000 person-years) in the ertugliflozin group than with the placebo group (6.0 vs 9.0); the HR (95% CI) was 0.66 (0.50, 0.88). At 60 months, in the ertugliflozin group, placebo-corrected changes from baseline (95% CIs) in UACR and eGFR were −16.2% (−23.9, −7.6) and 2.6 ml min−1 [1.73 m]−2 (1.5, 3.6), respectively. Ertugliflozin was associated with a consistent decrease in UACR and attenuation of eGFR decline across subgroups, with a suggested larger effect observed in the macroalbuminuria and Kidney Disease: Improving Global Outcomes in Chronic Kidney Disease (KDIGO CKD) high/very high-risk subgroups. Conclusions/interpretation Among individuals with type 2 diabetes and atherosclerotic CVD, ertugliflozin reduced the risk for the pre-specified exploratory composite renal endpoint and was associated with preservation of eGFR and reduced UACR. Trial registration ClinicalTrials.gov NCT01986881 Graphical abstract


Author(s):  
Nóra Kovács ◽  
Attila Nagy ◽  
Viktor Dombrádi ◽  
Klára Bíró

The prevalence of type 2 diabetes mellitus (T2DM) and the burden of complications are increasing worldwide. Chronic kidney disease (CKD) is one serious complication. Our aim was to investigate the trends and inequalities of the burden of CKD due to T2DM between 1990 and 2019. Data were obtained from the Global Health Data Exchange database. Age-standardized incidence, mortality, and DALYs rates of CKD were used to estimate the disease burden across the Human Development Index (HDI). Joinpoint regression was performed to assess changes in trend, and the Gini coefficient was used to assess health inequality. A higher incidence was observed in more developed countries (p < 0.001), while higher mortality and DALYs rates were experienced in low and middle HDI countries in 2019 (p < 0.001). The trend of incidence has increased since 1990 (AAPC: 0.9–1.5%), while slight decrease was observed in low HDI countries in mortality (APC: −0.1%) and DALYs (APC: −0.2%). The Gini coefficients of CKD incidence decreased from 0.25 in 2006 to 0.23 in 2019. The socioeconomic development was associated with disease burden. Our findings indicate that awareness of complications should be improved in countries with high incidence, and cost-effective preventive, diagnostic, and therapeutic tools are necessary to implement in less developed regions.


2021 ◽  
Vol 24 ◽  
pp. 157-166
Author(s):  
Wilailuck Tuntayothin ◽  
Stephen John Kerr ◽  
Chanchana Boonyakrai ◽  
Suwasin Udomkarnjananun ◽  
Sumitra Chukaew ◽  
...  

2021 ◽  
Vol 32 ◽  
pp. 100739
Author(s):  
Claire A Lawson ◽  
Samuel Seidu ◽  
Francesco Zaccardi ◽  
Gerry McCann ◽  
Umesh T Kadam ◽  
...  

Author(s):  
Julia Estela Willrich Böell ◽  
Denise Maria Guerreiro Vieira da Silva ◽  
Kathleen Mary Hegadoren

ABSTRACT Objective: to investigate the association between resilience and sociodemographic variables and the health of people with chronic kidney disease and / or type 2 diabetes mellitus. Method: a cross-sectional observational study performed with 603 people with chronic kidney disease and / or type 2 diabetes mellitus. A tool to collect socio-demographic and health data and the Resilience Scale developed by Connor and Davidson were applied. A descriptive and multivariate analysis was performed. Results: the study participants had on average 61 years old (SD= 13.2), with a stable union (52.24%), religion (96.7%), retired (49.09%), with primary education (65%) and income up to three minimum wages. Participants with kidney disease showed less resilience than people with diabetes. Conclusion: the type of chronic illness, disease duration, body mass index and religious beliefs influenced the resilience of the study participants.


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