Concurrent management of gout and type 2 diabetes mellitus: combined therapy insights.

The present study aims to determine the effects of sodium-glucose cotransporter 2 (SGLT-2) inhibitors on the serum uric acid (SUA) levels of patients with type 2 diabetes mellitus (T2DM) in Asia. PubMed, CENTRAL, Embase and Cochrane Library databases were searched for randomized controlled trials of SGLT-2 inhibitors in patients with T2DM up to 15 July 2021, without language or date restrictions. In total, 19 high-quality studies (4218 participants) were included in the present network meta-analysis. All of the included SGLT-2 inhibitors (empagliflozin, dapagliflozin, canagliflozin, ipragliflozin, luseogliflozin and tofogliflozin) significantly decreased SUA levels compared with those of the control [total standard mean difference -0.965, 95% CI (-1.029, -0.901), p= .000, I2 = 98.7%] in patients with T2DM. Subgroup analysis and meta-regression showed that the combined analysis of different inhibitors might lead to heterogeneity of the results. Therefore, among the SGLT-2 inhibitors, the results of the subsequent network meta-analysis revealed that luseogliflozin and dapagliflozin ranked the highest in terms of lowering SUA levels among the SGLT-2 inhibitors. Moreover, the network meta-analysis declared that luseogliflozin (1 and 10mg) and dapagliflozin (5mg) led to a superior reduction in SUA in patients with T2DM. SGLT-2 inhibitors could significantly reduce SUA levels in patients with T2DM, particularly luseogliflozin (1 and 10mg) and dapagliflozin (5mg) possess the best effects. Therefore, SGLT-2 inhibitors look extremely promising as an antidiabetes treatment option in patients with T2DM with high SUA.

Although sodium‐glucose cotransporter 2 (SGLT2) inhibitors lower serum uric acid, their long‐term effect on uric acid metabolism is not well understood. We analyzed pooled data from studies wherein patients with type 2 diabetes mellitus received luseogliflozin, an SGLT2 inhibitor. Upon stratifying patients by baseline glycated hemoglobin (HbA1c) or serum uric acid, lower HbA1c or higher serum uric acid level was associated with a greater reduction in serum uric acid after treatment. At week 12 of treatment, significant increases in urinary glucose/creatinine (Cr) ratio and urinary uric acid clearance/Cr clearance ratio (CUA/CCr ratio) and a significant reduction in serum uric acid were observed. Comparison of the subgroups of patients with a reduction or an increase in serum uric acid showed that the increase subgroup had a higher estimated glomerular filtration rate (eGFR) at baseline, and the eGFR was significantly reduced, associated with a significant reduction in the CUA/CCr ratio. Multiple regression analysis showed that the reduction in serum uric acid in the luseogliflozin group was strongly associated with baseline high serum uric acid, low HbA1c levels, and an increase in eGFR. Luseogliflozin was shown to reduce serum uric acid by enhancing urinary uric acid excretion in association with increased urinary glucose. Treatment with luseogliflozin resulted in increased serum uric acid in some patients, which may be due to reduced glomerular filtration of uric acid via the tubuloglomerular feedback. SGLT2 inhibitors reduced serum uric acid desirably in patients with type 2 diabetes mellitus with low HbA1c and high serum uric acid.

Background: Type 2 diabetes mellitus (T2DM) is a major public health problem affecting millions of people worldwide and its magnitude in developing countries including Bangladesh is rising rapidly. It is associated with multiple metabolic derangements that result in the excessive production of reactive oxygen species and oxidative stress. The major concern of health management in T2DM patients is to prevent diabetes-related complications which can only be achieved via strict glycemic control. Over the recent past it had been evident that serum bilirubin acts as a powerful antioxidant and upper limit of physiological ranges of serum bilirubin levels are beneficial and negatively associated with oxidative stress and glycemic status. Moreover, high serum uric acid plays an important role as an oxidative stress agent that is associated with poor glycemic control in diabetic subjects. Low serum bilirubin and high uric acid predicted a higher incidence for the development of T2DM and also had adverse impact on glycemic status. So, this study was designed to find out the association of serum bilirubin and uric acid with glycemic status among Type 2 diabetes mellitus subjects. Objective: To evaluate the association of serum bilirubin and uric acid with glycemic status in Type 2 diabetes mellitus. Materials and Methods: This cross-sectional analytical study was carried out in the department of Biochemistry, Sir Salimullah Medical College (SSMC), Dhaka from March, 2021 to February, 2022. A total number of 100 subjects were included in this study. Among them, 50 apparently healthy non-diabetic subjects age ranged from 30-59 years were considered as control group (Group A). Another 50 age and gender matched Type 2 diabetes mellitus patients without any complication were selected as study group (Group B). Ethical permission was taken from the Ethical Review Committee (ERC) of SSMC. All the study subjects were selected from the outpatient department of Medicine and Endocrinology, Sir Salimullah Medical College and Mitford Hospital, Dhaka. The study parameters were FPG, HbA1c, Serum bilirubin and serum uric acid. Estimation of study parameters were done in the Department of Biochemistry of SSMC, Dhaka. Statistical analysis was done by using SPSS version-22. Unpaired t test, Chi Square test, Pearson’s correlation test and Binary logistic regression were performed to analyze the data as applicable. Results: Serum bilirubin level was significantly lower and uric acid level was significantly higher among diabetic subjects in comparison to healthy controls. Comparison of glycemic status (FPG and HbA1c) in between different quartiles of serum bilirubin and uric acid in diabetic subjects were observed. FPG and HbA1c levels were significantly higher in Q1 & Q2 compared to Q3 & Q4 of serum bilirubin. However, FPG and HbA1c levels found high in Q3 & Q4 than Q1 & Q2 of uric acid. Pearson’s correlation analysis showed significant negative correlation of serum bilirubin with FPG and HbA1c, whereas significant positive correlation of serum uric acid with FPG and HbA1c were observed in study subjects. Binary logistic regression was performed to show the association between several factors and diabetes which were expressed by the coefficients of logistic regression. The risk of diabetes for each factor was expressed as odds ratio (OR). Coefficient for serum bilirubin (showing inverse relation) was significant. In case of serum uric acid, coefficient showed significant positive relationship. Where serum uric acid was strongest predictor of diabetes with an odds ratio of 3.709. Conclusion: Type 2 diabetic subjects have lower serum bilirubin and higher uric acid level than that of healthy subjects. Serum bilirubin has an inverse relationship with glycemic status (FPG and HbA1c), whereas uric acid shows positive correlation with glycemic status in diabetic subjects. Hyperuricemia appears to be a risk factor for development of Type 2 diabetes mellitus.

Background Several trials have assessed the antihyperglycemic effects of sodium/glucose cotransporter-2 inhibitors (SGLT2i) in patients with type 2 diabetes mellitus (T2DM). We conducted a quantitative analysis to assess the impact of SGLT2is on serum uric acid (SUA) in patients with T2DM. Methods Placebo-controlled trials published before 13 August 2021 were identified by searching PubMed, Embase, Web of Science, and Scopus. The intervention group received SGLT2i as monotherapy or add-on treatment, and the control group received a placebo that was replaced with SGLT2i. Clinical trials providing changes in SUA were included. The mean change of SUA, glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), and body weight were calculated (PROSPERO CRD42021287019). Results After screening of 1172 papers, 59 papers were included in the systematic review. A total of 55 trials (122 groups) of 7 types of SGLT2i on patients with T2DM were eligible for meta-analysis. All SGLT2is significantly decreased SUA levels compared with the placebo groups: empagliflozin mean difference (MD) = −40.98 μmol/L, 95% CI [-47.63, -34.32], dapagliflozin MD = −35.17 μmol/L, 95% CI [-39.68, -30.66], canagliflozin MD = −36.27 μmol/L, 95% CI [−41.62, −30.93], luseogliflozin MD = −24.269 μmol/L, 95% CI [-33.31, -15.22], tofogliflozin MD = −19.47 μmol/L, 95% CI [−27.40, −11.55], and ipragliflozin MD = −18.85 μmol/L, 95% CI [−27.20, −10.49]. SGLT2i also decreased FPG, body weight, and HbA1c levels. SUA reduction persisted during long-term treatment with SGLT2i (except for empagliflozin), while the SUA reduction was affected by the duration of diabetes. Conclusions SGLT2i can be a valid therapeutic strategy for patients with T2DM and comorbid hyperuricemia. Besides reducing FPG, body weight, and HbA1c, SGLT2i can significantly decrease SUA levels compared to placebo (Total MD = −34.07 μmol/L, 95% CI [-37.00, -31.14]).

BackgroundElevated serum uric acid (SUA) is strongly associated with adverse clinical outcomes. Sodium-glucose-cotransporter-2 (SGLT2) inhibitors not only lower blood glucose levels but also reduce UA. However, comparative data on the SUA-lowering effects among different SGLT2 inhibitors remain sparse, hindering evidence-based drug selection. This study aimed to systematically evaluate the effects of various SGLT2 inhibitors on SUA.MethodsWe searched the Cochrane Central Register of Controlled Trials (Ovid SP), Embase (Ovid SP), PubMed, and ClinicalTrials.gov up to March 2024 for randomized controlled trials (RCTs) evaluating SGLT2 inhibitors in patients with or without type 2 diabetes mellitus (T2DM). The primary outcome was the change in SUA levels compared with placebo. Data were analyzed using Review Manager 5.4. Pooled mean differences (MDs) for continuous outcomes (SUA change) and relative risk (RR) for dichotomous outcomes (gout incidence) were calculated. Study quality was evaluated using the Cochrane Risk of Bias tool (RoB 2), and the overall evidence quality was evaluated using the GRADE approach.ResultsA total of 51 RCTs were included in the meta-analysis. The SUA levels were significantly lower in all SGLT2 inhibitors groups than in the placebo groups. SGLT2 inhibitors have superior efficacy in lowering SUA levels compared with placebo [MD = −32.14 μmol/L, 95% CI (−35.96 to −28.31); P < 0.001]. Subgroup analysis showed empagliflozin achieved the greatest reduction in SUA [MD = −45.61 μmol/L, 95% CI (−52.26 to −38.97); P < 0.00001], while sotagliflozin had the least effect [MD = −13.72 μmol/L, 95% CI (−19.16 to −8.29); P < 0.00001]. The GRADE profiles indicated low-quality evidence for reduction in SUA levels. However, there was no difference in the incidence of gout between the two groups [RR = 0.96, 95% CI (0.77–1.21), P = 0.75].ConclusionSGLT2 inhibitors demonstrated greater SUA reduction than placebo, highlighting their potential as multifactorial therapies in high-risk populations.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/#loginpage, identifier CRD42023458993.

Kidney Effects of Empagliflozin in People with Type 1 Diabetes.

AimThis study investigated the effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors on renal outcomes in Asian patients with type 2 diabetes mellitus (T2DM).Materials and methodsWe searched Medline, EMBASE, and the Cochrane Library to identify randomized controlled trials published up to April 2020 that compared SGLT2 inhibitors with placebo or active comparator and reported any renal outcomes in Asian patients with T2DM. Random effects models and inverse variance weighting were used to calculate relative risks with 95% confidence intervals (CIs).ResultsWe included 14 studies, totaling 3792 patients, in the analysis. In the short term, SGLT2 inhibitors significantly slowed estimated glomerular filtration rate (eGFR) decline (MD: 0.80; 95% CI: 0.66 to 0.94; p < 0.00001) and reduced Scr levels (SMD: − 0.17; 95% CI: − 0.23 to − 0.10; p < 0.00001) as compared with the control groups. The SGLT2 inhibitor group also had an advantage over the control group in lowering uric acid (UA) (SMD: − 1.2; 95% CI: − 1.30 to − 1.11; p < 0.00001). There was no significant difference in urinary albumin creatinine ratio (UACR) reduction between the SGLT2 inhibitor and control groups (MD: − 8.87; 95% CI: − 19.80 to 2.06; p = 0.11). However, dapagliflozin does appear to reduce albuminuria (p = 0.005). Lastly, SGLT2 inhibitors increased the incidence of adverse events (AEs) related to renal function (OR: 1.90; 95% CI: 1.24 to 2.91; p = 0.003), but did not increase the incidence of renal impairment (OR: 0.85; 95% CI: 0.40 to 1.81; p = 0.68).ConclusionThe use of SGLT2 inhibitors in Asian patients with T2DM can help delay the decline of eGFR and reduce Scr and UA. Although SGLT2 inhibitors have no overall advantage in reducing albuminuria, dapagliflozin does appear to reduce albuminuria, and while they may increase the occurrence of AEs related to renal function, they do not increase the incidence of renal impairment.

In patients with type 2 diabetes mellitus (T2DM), controlling serum uric acid (SUA) and blood glucose levels is important. Moreover, sodium-glucose cotransporter 2 (SGLT2) inhibitors decrease SUA levels by accelerating urinary uric acid excretion. We investigated the effect of baseline urinary glucose levels on the relationship between SGLT2 inhibitors and SUA levels. We conducted a retrospective observational study using the electronic medical records of patients with T2DM of Kindai University Nara Hospital (April 2013 to March 2022). We divided the patients into two groups according to their baseline urinary glucose levels: the N-UG group, which included patients with negative urinary glucose strip test results (-), and the P-UG group, which included patients with positive urinary glucose strip test results (± or more). The changes in SUA levels before and after SGLT2 inhibitor administration were investigated. For comparison, the changes in SUA levels before and after the prescription of antidiabetic agents, excluding SGLT2 inhibitors, were also investigated. Our results revealed that SGLT2 inhibitors significantly decreased the SUA levels in patients in the N-UG group but tended to decrease its levels in those in the P-UG group. Regardless of the urinary glucose status at baseline, the administration of SGLT2 inhibitors may be useful for patients with T2DM to prevent the complications of hyperuricemia.

Hyperuricemia is a common comorbidity in patients with type 2 diabetes mellitus (T2DM), as insulin resistance (IR) or hyperinsulinemia is associated with higher serum uric acid (SUA) levels due to decreased uric acid (UA) secretion, and SUA vice versa is an important risk factor that promotes the occurrence and progression of T2DM and its complications. Growing evidence suggests that sodium-glucose cotransporter 2 inhibitors (SGLT-2i), a novel anti-diabetic drug initially developed to treat T2DM, may exert favorable effects in reducing SUA. Currently, one of the possible mechanisms is that SGLT2i increases urinary glucose excretion, probably inhibiting glucose transport 9 (GLUT9)-mediated uric acid reabsorption in the collecting duct, resulting in increased uric acid excretion in exchange for glucose reabsorption. Regardless of this possible mechanism, the underlying comprehensive mechanisms remain poorly elucidated. Therefore, in the present review, a variety of other potential mechanisms will be covered to identify the therapeutic role of SGLT-2i in hyperuricemia.

Type 2 diabetes mellitus (T2DM) patients are likely to develop kidney disease. The need to identify more accessible and cheaper diagnostic biomarkers cannot be overemphasized. This study investigated the ability of serum uric and uric acid to creatinine ratio in assessing the kidney function of T2DM patients and determined the relationship between serum uric acid to creatinine ratio and estimated glomerular filtration rate (eGFR). One hundred and fifty-five (155) consented T2DM patients were recruited from the diabetes clinic of the Cape Coast Teaching hospital. Anthropometric variables and blood pressure were measured. Serum uric acid (SUA), serum creatinine and urine protein were estimated using standard protocols. Uric acid to creatinine ratio (UA:CR), eGFR were then calculated. From the receiver operator characteristic (ROC) curve obtained, serum uric acid was found to be a better predictor of impaired renal function than UA:CR at p = 0.0001. The uric acid levels of participants in the fourth quartile of each category was found to be significant at p = 0.010 and can be used as indicators of kidney function in these participants. According to the odds ratio, the UA:CR will not be suitable to be used as an indicator of kidney function in any of the participants because their odds ratios were all less than 1. A total of 29(18.7 %) participants were found to have CKD with their eGFR falling below 60ml/mins per 1.73m2. A significant positive relationship was found between serum uric acid and the staging of CKD according to eGFR whiles a negative relationship was found with UA:CR and CKD (p < 0.0001). Serum uric acid is a better indicator of renal impairment (eGFR < 60ml/mins per 1.73m2) than UA:CR in patients with type 2 diabetes mellitus.

Sodium–glucose cotransporter 2 inhibitors (SGLT2i) exhibit renoprotective effect in patients with chronic kidney disease (CKD) and reduce serum uric acid (UA) in patients with diabetes mellitus. However, it is not clarified whether SGLT2i reduce serum UA levels in patients with advanced CKD. This study aimed to investigate the impact of SGLT2i on change in serum UA levels in patients with advanced CKD. Data of 121 Japanese patients with CKD who were newly administered 10 mg dapagliflozin in our department between August 2021 and August 2022 were analyzed. Changes in UA and fractional excretion of UA (FEUA) were analyzed using multiple regression analysis. Of 75 patients, 21 (28.0%) patients, 24 (32.0%) patients, 29 (38.7%) patients, and 1 (1.3%) patient were categorized as having CKD stage 3a, 3b, 4, and 5, respectively. The median age was 67 years, and 72.0% were male. 23 (30.7%) of patients had diabetes mellitus. The median estimated glomerular filtration rate, serum UA, and FEUA were 35.7 mL/min/1.73 m2, 6.4 mg/dL, and 6.76%, respectively, at the time of dapagliflozin administration. After administration, serum UA decreased to 5.6 mg/dL and FEUA increased to 9.22%. Dapagliflozin increases FEUA and reduces serum UA levels in patients with advanced CKD.

In the current issue of Circulation , Anker and colleagues1 report that elevated levels of uric acid (UA) predict mortality and the need for heart transplantation in patients with congestive heart failure (HF). Serum concentrations of UA added important prognostic information alone and when combined with measures of cardiac function (ejection fraction) and patient functional status (maximal oxygen consumption with exercise) and were independent of renal function, serum sodium, serum urea, diuretic usage, and patient age. Receiver operating curve analysis identified a cutoff of 585 μmol/L (9.8 mg/dL) as the best mortality predictor. This finding is not only potentially of value in patient management but also raises extremely interesting questions regarding the pathophysiological underpinnings of this finding. See p 1991 A consideration of the mechanism of UA production and metabolism offers insight into the relationship between UA levels and HF outcomes. Indeed, accumulating data support the idea that UA, in addition to being a potentially valuable prognostic marker, possesses specific toxic or other properties that could contribute to HF pathophysiology. Moreover, UA levels may reflect xanthine oxidase (XO) pathway activity, which has the potential to contribute to the progression of left ventricular dysfunction by interfering with myocardial energetics2 and myofilament calcium sensitivity.3 UA is a metabolic byproduct of purine metabolism (Figure). Serum UA may increase in the failing circulation because of increased generation, decreased excretion, or a combination of the 2 factors. There are several possible contributors to increased UA production in HF, including increased abundance and activity of XO,4 increased conversion of …

Objective To investigate the relationship between the level of serum uric acid(SUA) and carotid atherosclerosis in male patients with type 2 diabetes mellitus(T2DM). Methods A collection of 579 male T2DM patients with or without carotid atherosclerosis were grouped based on quartiles of SUA. Age, SUA, smokers, duration, body mass index(BMI), blood pressure, total cholesterol(TC), triglyceride(TG), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), blood urea nitrogen(BUN), creatinine(Cr), and HbA1C were determined in all subjects. The plaques in carotid arteries and intima-media thickness(IMT) were measured with high-resolution ultrasound. Results BMI, systolic and diastolic blood pressures, TG, and Cr showed a gradual increase, while HDL-C and HbA1C showed a gradual decrease according to the higher SUA quartiles in male T2DM(P＜0.05). Nevertheless, the detectable rates of smokers, duration, age, TC, LDL-C, and BUN had no relationships with the SUA quartiles(P＞0.05). The detectable rate of carotid atherosclerosis and the thickness of carotid plaque were positively associated with the levels of SUA in male patients with T2DM(P＜0.05). However, intima-media thickness of carotid arteries did not illustrate the correlation with the levels of SUA in male T2DM patients(P＞0.05). Age, HbA1C, and SUA were independent factors of carotid atherosclerosis in these patients by logistic regression(P＜0.05). Conclusion The levels of SUA seems to be associated with the occurrence and development of carotid atherosclerosis in male patients with T2DM. Key words: Diabetes mellitus, type 2; Serum uric acid; Carotid atherosclerosis; Male

Hippocrates would not be surprised to read that persons with gout had higher mortality, and particularly cardiovascular-related mortality, than persons without gout.1 On the other hand, he might well have been bemused, nearly 2500 years after he described the syndrome, that this made news. Article p 894 He should not have been. All too often, rigorous examination debunks conventional wisdom. Reassuringly, in this case, Drs Choi and Curhan found evidence to support long-standing belief. These dedicated and productive students of the pathogenesis and natural history of gout have here reported empiric data from the 51 000 male nonphysician health professionals who participated in the Health Professions Follow-up Study. From initial examination in 1986 through nearly 600 000 person-years of follow-up, 5825 deaths occurred, of which 2132 were cardiovascular and 1576 were ascribed to coronary heart disease, rates that attest to the generally good health of the group. The ≈6% prevalence of gout, at baseline, in men in their mid-50s, who mirror the general US population in body mass index, reported history of hypertension, hypercholesterolemia, and diabetes mellitus, was higher than expected. Interim biennial questionnaires identified incident cases of gout. Participants with gout were both more likely to report coronary heart disease (CHD) at baseline and, regardless of CHD status, more likely than gout-free persons to have cardiovascular disease (CVD) risk factors. Results were presented after stratification by CHD status at baseline. As expected, the incidence of all-cause and CHD mortality was much greater in those with than in those without prevalent CHD. The adjusted increased relative risk of those with gout (compared with those without) for all-cause, CVD, and CHD mortality was ≈25%. The single exception was a near doubling of increased relative risk of CHD mortality among those free of CHD at baseline. Neither the inclusion of incident …

New Therapies for Diabetes Management