Clinical Edge Journal Scan Commentary: Type 2 DM May 2022

Heart failure with preserved ejection fraction (HFpEF) is common in elderly adults with type 2 diabetes (T2D), and these individuals are at high risk for frailty and cognitive impairment. Empagliflozin has been shown to reduce cardiovascular death or hospitalization for heart failure in individuals with HFpEF with or without diabetes, but little is known about the impact of empagliflozin on cognition in patients with diabetes and HFpEF. In a prospective observation study of 162 frail older adults with T2D and HFpEF, Mone and colleagues reported that after receiving empagliflozin for 1 month, there was a significant improvement in the Montreal Cognitive Assessment score, but no improvement was seen with metformin or insulin. Although the study was limited by its observational design, small sample size, and short follow-up, it indicates that improved cognition may be another unexpected benefit of empagliflozin in patients with HFpEF.

The Action to Control Cardiovascular Risk in Diabetes (ACCORD) study continues to provide valuable information for the management of T2D. ACCORD Lipid had previously shown that fenofibrate vs. placebo added to simvastatin did not reduce major atherosclerotic cardiovascular events in about 5500 patients with T2D who were at high risk for cardiovascular disease. Ferreira and colleagues have now reported that fenofibrate in ACCORD Lipid reduced hospitalization for heart failure or cardiovascular death by 18%, with the benefit predominantly in those treated with standard glucose-lowering therapy. This analysis was done post hoc and is hypothesis-generating for fenofibrate reducing HF-related events. The soon to be completed PROMINENT study of pemafibrate includes a secondary composite cardiovascular outcome with hospitalization for heart failure as a component, so more information regarding the impact of fibrates on heart failure will be available soon.

Diabetes is associated with a threefold greater risk for stroke and microvascular disease. In another analysis of ACCORD, Kaze and colleagues reported that a higher urine albumin‐to‐creatinine ratio and a lower estimated glomerular filtration rate were each independently associated with an increased risk for stroke. Although further adequately powered studies are required, this analysis suggests that prevention of kidney disease and its progression may help mitigate the risk for stroke in people with T2D.

People with severe mental illness (SMI), such as schizophrenia, bipolar disorder, or depression, are at increased risk for T2D, but it is unknown whether they are more likely to develop the complications of diabetes. Scheuer and colleagues published data from a large nationwide registry in Denmark. They found that, compared with people without SMI, people with SMI were more likely to develop nephropathy or cardiovascular disease, have an amputation, and that the nephropathy and cardiovascular disease occurred at younger ages in those with SMI. Although there are limitations with registry data, this study supports diabetes guidelines that recommend cardiorenal protection with sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists in patients with T2D who are at high risk for nephropathy progression and cardiovascular disease. Because this study suggests that SMI along with T2D confers greater risk for nephropathy and cardiovascular disease at younger ages, perhaps we should consider these cardiorenal protective agents early on in persons with T2D and SMI.

Heart failure with preserved ejection fraction (HFpEF) is common in elderly adults with type 2 diabetes (T2D), and these individuals are at high risk for frailty and cognitive impairment. Empagliflozin has been shown to reduce cardiovascular death or hospitalization for heart failure in individuals with HFpEF with or without diabetes, but little is known about the impact of empagliflozin on cognition in patients with diabetes and HFpEF. In a prospective observation study of 162 frail older adults with T2D and HFpEF, Mone and colleagues reported that after receiving empagliflozin for 1 month, there was a significant improvement in the Montreal Cognitive Assessment score, but no improvement was seen with metformin or insulin. Although the study was limited by its observational design, small sample size, and short follow-up, it indicates that improved cognition may be another unexpected benefit of empagliflozin in patients with HFpEF.

The Action to Control Cardiovascular Risk in Diabetes (ACCORD) study continues to provide valuable information for the management of T2D. ACCORD Lipid had previously shown that fenofibrate vs. placebo added to simvastatin did not reduce major atherosclerotic cardiovascular events in about 5500 patients with T2D who were at high risk for cardiovascular disease. Ferreira and colleagues have now reported that fenofibrate in ACCORD Lipid reduced hospitalization for heart failure or cardiovascular death by 18%, with the benefit predominantly in those treated with standard glucose-lowering therapy. This analysis was done post hoc and is hypothesis-generating for fenofibrate reducing HF-related events. The soon to be completed PROMINENT study of pemafibrate includes a secondary composite cardiovascular outcome with hospitalization for heart failure as a component, so more information regarding the impact of fibrates on heart failure will be available soon.

Diabetes is associated with a threefold greater risk for stroke and microvascular disease. In another analysis of ACCORD, Kaze and colleagues reported that a higher urine albumin‐to‐creatinine ratio and a lower estimated glomerular filtration rate were each independently associated with an increased risk for stroke. Although further adequately powered studies are required, this analysis suggests that prevention of kidney disease and its progression may help mitigate the risk for stroke in people with T2D.

People with severe mental illness (SMI), such as schizophrenia, bipolar disorder, or depression, are at increased risk for T2D, but it is unknown whether they are more likely to develop the complications of diabetes. Scheuer and colleagues published data from a large nationwide registry in Denmark. They found that, compared with people without SMI, people with SMI were more likely to develop nephropathy or cardiovascular disease, have an amputation, and that the nephropathy and cardiovascular disease occurred at younger ages in those with SMI. Although there are limitations with registry data, this study supports diabetes guidelines that recommend cardiorenal protection with sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists in patients with T2D who are at high risk for nephropathy progression and cardiovascular disease. Because this study suggests that SMI along with T2D confers greater risk for nephropathy and cardiovascular disease at younger ages, perhaps we should consider these cardiorenal protective agents early on in persons with T2D and SMI.

Heart failure with preserved ejection fraction (HFpEF) is common in elderly adults with type 2 diabetes (T2D), and these individuals are at high risk for frailty and cognitive impairment. Empagliflozin has been shown to reduce cardiovascular death or hospitalization for heart failure in individuals with HFpEF with or without diabetes, but little is known about the impact of empagliflozin on cognition in patients with diabetes and HFpEF. In a prospective observation study of 162 frail older adults with T2D and HFpEF, Mone and colleagues reported that after receiving empagliflozin for 1 month, there was a significant improvement in the Montreal Cognitive Assessment score, but no improvement was seen with metformin or insulin. Although the study was limited by its observational design, small sample size, and short follow-up, it indicates that improved cognition may be another unexpected benefit of empagliflozin in patients with HFpEF.

The Action to Control Cardiovascular Risk in Diabetes (ACCORD) study continues to provide valuable information for the management of T2D. ACCORD Lipid had previously shown that fenofibrate vs. placebo added to simvastatin did not reduce major atherosclerotic cardiovascular events in about 5500 patients with T2D who were at high risk for cardiovascular disease. Ferreira and colleagues have now reported that fenofibrate in ACCORD Lipid reduced hospitalization for heart failure or cardiovascular death by 18%, with the benefit predominantly in those treated with standard glucose-lowering therapy. This analysis was done post hoc and is hypothesis-generating for fenofibrate reducing HF-related events. The soon to be completed PROMINENT study of pemafibrate includes a secondary composite cardiovascular outcome with hospitalization for heart failure as a component, so more information regarding the impact of fibrates on heart failure will be available soon.

Diabetes is associated with a threefold greater risk for stroke and microvascular disease. In another analysis of ACCORD, Kaze and colleagues reported that a higher urine albumin‐to‐creatinine ratio and a lower estimated glomerular filtration rate were each independently associated with an increased risk for stroke. Although further adequately powered studies are required, this analysis suggests that prevention of kidney disease and its progression may help mitigate the risk for stroke in people with T2D.

People with severe mental illness (SMI), such as schizophrenia, bipolar disorder, or depression, are at increased risk for T2D, but it is unknown whether they are more likely to develop the complications of diabetes. Scheuer and colleagues published data from a large nationwide registry in Denmark. They found that, compared with people without SMI, people with SMI were more likely to develop nephropathy or cardiovascular disease, have an amputation, and that the nephropathy and cardiovascular disease occurred at younger ages in those with SMI. Although there are limitations with registry data, this study supports diabetes guidelines that recommend cardiorenal protection with sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists in patients with T2D who are at high risk for nephropathy progression and cardiovascular disease. Because this study suggests that SMI along with T2D confers greater risk for nephropathy and cardiovascular disease at younger ages, perhaps we should consider these cardiorenal protective agents early on in persons with T2D and SMI.