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Aim: To assess the association between urinary albumin‐to‐creatinine ratio (UACR) categories within the normal range with mortality and adverse cardiovascular outcomes. Materials and Methods: PubMed and Embase were systematically searched for real‐world evidence studies. Studies were manually evaluated according to predefined eligibility criteria. We included prospective and retrospective cohort studies of the association between UACR categories <30 mg/g and cardiovascular outcomes or mortality. Published information regarding study design, participants, UACR categorization, statistical methods, and results was manually collected. Two UACR categorization approaches were defined: a two‐category (UACR <10 mg/g vs. 10‐30 mg/g) and a three‐category division (UACR <5 mg/g vs. 5‐10 and 10‐30 mg/g). A random effects meta‐analysis was performed on studies eligible for the meta‐analysis. Results: In total, 22 manuscripts were identified for the systematic review, 15 of which were eligible for the meta‐analysis. The results suggest an association between elevated UACR within the normal to mildly increased range and higher risks of all‐cause mortality, cardiovascular death, and coronary heart disease, particularly in the range of 10‐30 mg/g. Compared with UACR <10 mg/g, the hazard ratio [HR (95% confidence interval, CI)] for UACR between 10 and 30 mg/g was 1.41 (1.15, 1.74) for all‐cause mortality and 1.56 (1.23, 1.98) for coronary heart disease. Compared with UACR <5 mg/g, the risk of cardiovascular mortality for UACR between 10 and 30 mg/g was more than twofold [HR (95% CI): 2.12 (1.61, 2.80)]. Intermediate UACR (5‐10 mg/g) was also associated with a higher risk of all‐cause mortality [HR (95% CI): 1.14 (1.05, 1.24)] and cardiovascular mortality [HR (95% CI): 1.50 (1.14, 1.99)]. Conclusions: We propose considering higher UACR within the normoalbuminuric range as a prognostic factor for cardiovascular morbidity and mortality. Our findings underscore the clinical significance of even mild increases in albuminuria. [ABSTRACT FROM AUTHOR]

Following propensity-score matching, there were 6477 patients in each arm; 5431 patients (41.9%) were women and the mean (SD) patient age was 59.8 (10.9) years (Table 1). Patients with T2D, who initiated an SGLT2 inhibitor (empagliflozin or dapagliflozin) in an outpatient setting between August 2015 and December 2020 were propensity-scored matched with patients starting a DPP-4 inhibitor (sitagliptin, linagliptin, vildagliptin or saxagliptin). Risk of hospitalization with sodium-glucose cotransporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes lacking evidence of chronic kidney disease: Real-world data Patients with type 2 diabetes (T2D) have a high incidence of hospitalizations that reduce patients' quality of life and are translated into a significant burden on healthcare systems, accompanied by increased costs.[[1]] Randomized controlled trials (RCTs) showed that sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of cardiovascular events, heart failure (HF) hospitalizations, and kidney outcomes in patients with T2D, HF, or chronic kidney disease (CKD).[3] In some of these RCTs, SGLT2 inhibitors also modestly reduced the risk for any hospitalization.[[4], [6], [8], [10]] However, these studies included patients with T2D and high cardiovascular risk,[[4], [6], [11]] or patients with CKD with and without T2D.[[8]] Whether SGLT2 inhibitor use is associated with a lower risk for any hospitalization in a general population of patients with T2D, especially patients without CKD, is unknown. [Extracted from the article]

Objective: To examine the efficacy and safety of Curalin supplement in patients with type 2 diabetes. Research design and methods: Adult patients with type 2 diabetes were randomized 1:1 to receive Curalin supplement or placebo. The primary endpoint was HbA1c decrease at 1 month. The secondary endpoint was a decrease in HbA1c by more than 0.5% and 1% and a change in 7 daily blood glucose measurements. A satisfaction questionnaire was used as an exploratory endpoint. Safety variables and adverse events were assessed. Results: After 1 month of intervention, HbA1c was reduced by 0.94% in the Curalin arm versus 0.4% in the placebo arm (P = 0.008). 72% of Curalin patients had decreased HbA1c levels >0.5% versus 35% in the placebo arm (P < 0.05). The Treatment Satisfaction Questionnaire indicated that Curalin arm patients reported higher overall satisfaction. Conclusions: Curalin treatment significantly reduced HbA1c over a 1‐month period and was well‐tolerated. [ABSTRACT FROM AUTHOR]

Aim: To assess the associations between baseline glucose‐lowering agents (GLAs) and cardiorenal outcomes with dapagliflozin versus placebo in the DECLARE‐TIMI 58 study. Materials and methods: DECLARE‐TIMI 58 assessed the cardiorenal outcomes of dapagliflozin versus placebo in patients with type 2 diabetes. This post hoc analysis elaborates the efficacy and safety outcomes by baseline GLA for treatment effect and GLA‐based treatment interaction. Results: At baseline, 14 068 patients (82.0%) used metformin, 7322 (42.7%) sulphonylureas, 2888 (16.8%) dipeptidyl peptidase‐4 inhibitors, 750 (4.4%) glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) and 7013 (40.9%) insulin. Dapagliflozin reduced the composite of cardiovascular death (CVD) and hospitalization for heart failure (HHF) versus placebo regardless of baseline GLA, with greater benefit in the small group of patients with baseline use of GLP‐1 RAs (HR [95% CI] 0.37 [0.18, 0.78] vs. 0.86 [0.75, 0.98] in GLP‐1 RA users vs. non‐users, Pinteraction =.03). The overall HR for major adverse cardiovascular events (CVD, myocardial infarction or ischaemic stroke) was 0.93 (95% CI 0.84, 1.03) with dapagliflozin versus placebo, with no interaction by baseline GLA (Pinteraction >.05). The renal‐specific outcome was reduced with dapagliflozin versus placebo in the overall cohort (HR [95%CI] 0.53[0.43‐0.66]), with no interaction by baseline GLA (Pinteraction >.05). All of these outcomes were similar in those with versus those without baseline metformin use. Conclusions: The effects of dapagliflozin on cardiorenal outcomes were generally consistent regardless of baseline GLA, with consistent benefits regardless of baseline metformin use. The potential clinical benefit of combining sodium‐glucose co‐transporter‐2 inhibitors with GLP‐1 RAs, given some evidence of cardiovascular risk reduction with both classes, should be explored further. [ABSTRACT FROM AUTHOR]

Aims: To evaluate comprehensively the safety of dapagliflozin in patients with type 2 diabetes (T2DM), with emphasis placed on potential safety concerns related to the sodium‐glucose co‐transporter‐2 inhibitor class. Methods: In the Dapagliflozin Effect on Cardiovascular Events – Thrombolysis in Myocardial Infarction 58 (DECLARE‐TIMI 58) study, 17 160 patients with T2DM were randomized to dapagliflozin or placebo and followed for a median of 4.2 years. Safety was evaluated in 17 143 patients receiving at least one dose of study drug. Results: Acute kidney injury occurred less frequently with dapagliflozin, and adverse events suggestive of volume depletion were balanced between treatment groups, both irrespective of baseline estimated glomerular filtration rate, blood pressure, diuretic or loop diuretic use (interaction P values >0.05). Fractures and malignancies were balanced between the groups, irrespective of sex, diabetes duration or smoking (interaction P values >0.05) and fewer cases of bladder cancer occurred in the dapagliflozin versus the placebo group. Diabetic ketoacidosis was very rare, but more frequent with dapagliflozin versus placebo (27 vs. 12 patients with events; P = 0.02), yet signs, symptoms and contributing factors were similar in the two groups. Major hypoglycaemia occurred less frequently with dapagliflozin versus placebo, regardless of baseline use of either insulin or sulphonylureas (interaction P values >0.05). There were more adverse events of genital infections leading to discontinuation of study drug in the dapagliflozin versus the placebo group, but serious genital infections were few and balanced between treatment groups. Urinary tract infections, acute pyelonephritis and urosepsis were also balanced between treatment groups. Conclusions: Dapagliflozin was well tolerated. The long duration and large number of patient‐years in DECLARE‐TIMI 58 comprehensively addressed previous safety questions, confirming the robust safety profile of dapagliflozin. [ABSTRACT FROM AUTHOR]

Aim: To investigate whether the cardiovascular and renal benefits observed with dapagliflozin in the DECLARE‐TIMI 58 trial are also observed in patients with short and long‐standing diabetes. Materials and Methods: This post hoc analysis studied the dual primary efficacy endpoints, a composite of cardiovascular death or hospitalization for heart failure (CVD/HHF) and major adverse cardiovascular events (MACE; CVD, myocardial infarction [MI], ischaemic stroke) by diabetes duration. Results: Of the 17 160 patients, 3836 had diabetes duration of ≤5 years, 4731 >5‐10 years, 3952 >10‐15 years, 2433 >15‐20 years and 2206 >20 years. Dapagliflozin reduced the risk of CVD/HHF by a similar amount across diabetes duration subgroups, ranging from HR 0.79 (0.58‐1.06) in patients with diabetes duration of ≤5 years to 0.75 (0.55‐1.03) in those patients with diabetes duration of >20 years (interaction trend P‐value 0.76). Hazard ratios (HRs) for MACE ranged from 1.08 (0.87‐1.35) in patients with diabetes duration of ≤5 years to 0.67 (0.52‐0.86) in those patients with diabetes duration of >20 years (interaction trend P‐value 0.004). This was driven by greater reductions in the risk of MI and ischaemic stroke with dapagliflozin in patients with long‐standing diabetes (interaction trend P‐values 0.019 and 0.015, respectively). The duration‐based MACE heterogeneity was apparent in those with or without a history of prior MI and in those with multiple risk factors. The renal‐specific outcome was reduced with dapagliflozin with HRs ranging from 0.79 (0.47‐1.34) in patients with diabetes duration of ≤5 years to 0.42 (0.25‐0.72) in those patients with diabetes duration of >20 years (interaction trend P‐value 0.084). Conclusions: Dapagliflozin reduced the risk of CVD/HHF consistently, regardless of diabetes duration, whereas the treatment effect for MACE differed by duration subgroups, with significant reductions with dapagliflozin in patients with long‐standing diabetes. [ABSTRACT FROM AUTHOR]

Objectives: To determine the association between frequency of leaving the house and mortality. Design: Prospective follow‐up of an age‐homogenous, representative, community‐dwelling birth cohort (born 1920–21) from the Jerusalem Longitudinal Study (1990–2015). Setting: Home. Participants: Individuals aged 70 (n = 593), 78 (n = 973), 85 (n = 1164), and 90 (n = 645), examined in 1990, 1998, 2005, and 2010, respectively. Measurements: Frequency of leaving the house, defined as daily (6–7/week), often (2–5/week), and rarely (≤1/week); geriatric assessment; all‐cause mortality (2010–15). Kaplan‐Meier survival charts and proportional hazards models adjusted for social (sex, marital status, financial status, loneliness), functional (sex, self‐rated health, fatigue, depression, physical activity, activity of daily living difficulty), and medical (sex, chronic pain, visual impairment, hearing impairment, diabetes mellitus, hypertension, ischemic heart disease, chronic kidney disease) covariates. Results: At ages 70, 78, 85, and 90, frequency of going out daily was 87.0%, 80.6%, 65.6%, and 48.4%; often was 6.4%, 9.5%, 17.4%, and 11.3%; and rarely was 6.6%, 10.0%, 17.0%, and 40.3% respectively. Decreasing frequency of going out was associated with negative social, functional, and medical characteristics. Survival rates were lowest among those leaving rarely and highest among those going out daily throughout follow‐up. Similarly, compared with rarely leaving the house, unadjusted mortality hazard ratios (HRs) were lowest among subjects leaving daily and remained significant after adjustment for social, functional and medical covariates. Among subjects leaving often, unadjusted HRs showed a similar effect of smaller magnitude, with attenuation of significance after adjustment in certain models. Findings were unchanged after excluding subjects dying within 6 months of follow‐up. Conclusion: In community‐dwelling elderly adults aged 70 to 90, leaving the house daily was associated with lower mortality risk, independent of social, functional, or medical status. [ABSTRACT FROM AUTHOR]

Hypoglycaemia is a well-known risk associated with the use of sulphonylureas and insulin, often limiting achievement of glycaemic goals. Recognizing the precipitants and recurrence patterns of hypoglycaemic events, particularly major events, is therefore clinically important. The SAVOR-TIMI-53 trial was a cardiovascular outcome study of 16 492 patients allocated to saxagliptin vs placebo added to conventional care for a median of 2.1 years. Hypoglycaemic events were a prespecified outcome in the study and were defined as a symptomatic episode that recovered with carbohydrates or any recorded blood glucose <3.0 mmol/l (<54 mg/ dL). A major event was defined as one that required third-party assistance. Analysis of the features of the first hypoglycaemic event for each patient showed that a precipitant for the event was recognized by fewer than half of the patients, with the precipitant most often being a missed meal. In 40% of patients reporting major hypoglycaemic events, no precipitating factor was recognized, and in >60%, no previous hypoglycaemic event was reported during the timespan of the study, underscoring the lack of predictability of such an event. [ABSTRACT FROM AUTHOR]

Objectives To determine the trajectory of handgrip strength ( HGS) from age 70 to 90 and its association with mood, cognition, functional status, and mortality. Design Prospective follow-up of an age-homogenous representative community-dwelling cohort (born 1920-21) in the Jerusalem Longitudinal Cohort Study (1990-2015). Setting Home-based assessment. Participants Subjects aged 70 (n = 327), 78 (n = 384), 85 (n = 1187), and 90 (n = 406), examined in 1990, 1998, 2005, and 2010, respectively. Measurements Handgrip strength (kg) (dynamometer), low HGS defined as sex-specific lowest quartile grip; geriatric assessment; all-cause mortality (1990-2015). Results Mean HGS declined between age 70 and 90 from 21.3 ± 7.2 to 11.5 ± 5.6 kg in women and from 35.3 ± 8.4 to 19.5 ± 8.2 kg in men. Cross-sectional associations were observed between low HGS and poor functional measures (age 70-90), lower educational and financial status, smoking, and diabetes mellitus (ages 78-90). After adjustment for baseline education, self-rated health, physical activity, diabetes mellitus, depression, and cognition, low HGS predicted subsequent activity of daily living dependence from age 78 to 85 (odds ratio ( OR) = 2.68, 95% confidence interval ( CI) = 1.04-6.89) and 85 to 90 ( OR = 2.31, 95% CI = 1.01-5.30), whereas the adjusted ORs for activities of daily living difficulty and depression failed to achieve significance. HGS did not predict subsequent cognitive decline. Survival rates were significantly lower in participants with low HGS (Quartile 1) than in those with normal HGS (Quartiles 2, 3, 4) throughout follow-up from ages 78 to 85, 85 to 90, and 90 to 95. Similarly, after adjusting for sex, education, self-rated health, body mass index, hypertension, diabetes mellitus, ischemic heart disease, and smoking, a low HGS was associated with significantly higher mortality. Conclusions Mean HGS declined progressively with age, and participants in the lowest age-specific quartile of HGS had a higher risk of subsequent functional decline and mortality. [ABSTRACT FROM AUTHOR]