Glucose-lowering Drugs Research Articles

Anti-Diabetic Agents in Covid-19, Their Possible Role Beyond Diabetes

Recent reports from various observational investigations revealed and published the outcomes of Non-insulin Anti-diabetic agents. Patients additionally with Type-II Diabetes Mellitus and coronavirus disease, caused by severe acute respiratory syndrome [SARS] has become widespread disease in the world since last 3 years. Age, sex, ethnicity, obesity and co-morbidities all apparently enhance the risk of worst consequences. Glucose lowering drugs and anti-viral drug treatment could limit the risk but impose restrictions on their usage which needs to be carefully assessed. This severe acute respiratory syndrome [coronavirus] might be a potentially triggering and worsen the aspect for the diabetic patients that can bring about severe metabolic complications effecting β-cell function leading to hyperglycaemia and diabetic ketoacidosis.

The Effect of Different Glucose Concentrations on the Antiproliferative Activity of Metformin in MCF-7 Breast Cancer Cells.

The glucose-lowering drug metformin has been reported to have anticancer properties through unknown mechanisms. Other unknown factors that may influence its anticancer potential include the glycemic status of the patient. Therefore, the objective of this study is to determine the effect of different glucose environments on the antiproliferative potency and the cellular mechanism of action of metformin. Human breast cancer cells, MCF-7, were incubated in low, normal, elevated, and high glucose environments and treated with metformin. The antiproliferative potential of metformin and its effect on protein expression as well as its ability to induce cellular apoptosis and autophagy under different glucose environments, were determined using different molecular techniques. Metformin significantly inhibited cellular proliferation in a time- and glucose-concentration-dependent manner. In comparison to elevated glucose, low normal glucose alone induced a significant level of autophagy that was further increased in the presence of metformin. While glucose concentration did not appear to have an effect on the antiproliferative potency of metformin, the cellular basis of action was shown to be glucose-dependent. The antiproliferative mechanism of action of metformin in elevated and low normal glucose environments is mTOR-dependent, whereas, in the high glucose environment, the antiproliferative mechanism is independent of mTOR. This is the first study to report that both the antiproliferative potency and the cellular mechanism of action aredependent on the concentration of glucose.

Correlation of various lipid-lowering and hypoglycemic drugs with the risk of gastric cancer in elderly population

Purpose: To investigate the correlation between several lipid-lowering and hypoglycemic drugs and the risk of gastric cancer (GC) in elderly population.Methods: A total of 160 elderly patients with GC who attended The First Affiliated Hospital of Henan University of Science and Technology from January 1, 2014 to December 31, 2020 were enrolled in the study group. Furthermore, 320 healthy volunteers within the same period were assigned to the control group. Clinical data (such as history of statin, sulfonylurea and biguanide administration) were collected from the patient’s medical records. Multifactorial logistic regression was used to determine the association between these lipid-lowering and glucose-lowering drugs, and the risk of developing GC.Results: After adjusting for numerous confounding factors, multifactorial logistic regression showed that long-term use (>12 months of treatment) of statins and biguanides significantly reduced the risk of GC in elderly population (p = 0.006, p = 0.004, respectively), while long-term use of sulphonylureas increased the risk of GC in elderly population (p = 0.004).Conclusion: Statins, sulfonylureas and biguanides may be closely associated with the development of GC in elderly population. Therefore, a detailed understanding of the efficacy and mechanisms of action of these drugs may benefit the elderly in the prevention and control of GC.

Place of metformin in modern clinical guidelines for the treatment of type 2 diabetes mellitus

Diabetes mellitus is one of the most common endocrine diseases. Type 2 diabetes mellitus is associated with high cardiovascular morbidity and mortality and is a leading cause of chronic kidney disease and end-stage kidney disease. To date, for the treatment of patients with type 2 diabetes, hypoglycemic drugs are used that affect different parts of the pathogenesis. Metformin is a biguanide that is used in the treatment of type 2 diabetes mellitus; it is effective as monotherapy and in combination with other glucose-lowering medications. In addition to the treatment of diabetes mellitus, metformin is recommended and widely used for the treatment of prediabetes. Metformin is generally well-tolerated with minimal side effects and is affordable. Metformin is very effective in HbA1c lowering associated with some weight loss, but does not increase risk for hypoglycemia. With the use of metformin in monotherapy, the decrease in HbA1c levels is 1–2%. Despite the appearance in practice of a fairly large number of new, effective glucose-lowering drugs, metformin is still the drug of choice in many cases. And most diabetic associations recommend metformin as a first-line drug. Metformin has demonstrated many positive effects in observational studies in patients with CAD, heart failure, and chronic kidney disease. This review presents data on the efficacy and, pleiotropic effects of metformin. Possible adverse events are also discussed, including the risk of low level and deficiency of vitamin B12, gastrointestinal tract adverse events.

Efficacy of Regimens in the Treatment of Latent Autoimmune Diabetes in Adults: A Network Meta-analysis.

Latent autoimmune diabetes in adults (LADA) is a highly heterogeneous autoimmune condition with clinical and genetic characteristics that fall between those of type 1 diabetes mellitus and type 2 diabetes mellitus; therefore, there are no uniform criteria for the selection of therapeutic agents. We conducted a network meta-analysis to evaluate the efficacy of various therapeutic agents for LADA by comparing their effects on various indicators used to reflect LADA. We searched the PubMed, Cochrane Library, Embase and Web of Science databases from their inception to March 2023 and collected data from 14 randomized controlled trials on glucose-lowering drugs for LADA, including 23 studies and 15 treatment regimens. The effectiveness of drugs was ranked and evaluated by combining surface under the cumulative ranking (SUCRA) plots and forest plots. Factors that may influence study heterogeneity were also searched and analyzed by combining subgroup analysis, publication bias, funnel plots and sensitivity analysis. The results of the network meta-analysis showed that insulin had the most significant effect on the control of change from baseline in glycosylated hemoglobin, type A1 (ΔHbA1c). Insulin combined with dipeptidyl peptidase-4 (DPP-4) inhibitors performed the best in reducing fasting blood glucose and body mass index. Treatment regimens involving thiazolidinediones were the most advantageous in HbA1c, fasting C-peptide and postprandial C-peptide control. Longer dosing may be more beneficial in maintaining islet β-cell function in the LADA population. LADA is an immune condition with high heterogeneity, and treatment should be administered according to the C-peptide level of the LADA population. For this population with LADA with a certain level of β-cell function, combinations of insulin with DPP-4 inhibitors or thiazolidinediones probably can be more effective treatment options to maintain islet function and normal blood glucose. PROSPERO CRD42023410795.

Targeting BCAA metabolism to potentiate metformin's therapeutic efficacy in the treatment of diabetes in mice.

An increasing body of evidence has shown that the catabolism of branched-chain amino acids (BCAAs; leucine, isoleucine and valine) is impaired in obese animals and humans, contributing to the development of insulin resistance and type 2 diabetes. Promoting BCAA catabolism benefits glycaemic control. It remains unclear whether BCAA catabolism plays a role in the therapeutic efficacy of currently used glucose-lowering drugs such as metformin. Mice were treated with vehicle or metformin (250 mg/kg per day) for more than 4 weeks to investigate the effects of metformin in vivo. In vitro, primary mouse hepatocytes and HepG2 cells were treated with 2 mmol/l metformin. The therapeutic efficacy of metformin in the treatment of type 2 diabetes was assessed in genetically obese (ob/ob) mice and high-fat-diet-induced obese (DIO) mice. Enhancing BCAA catabolism was achieved with a pharmacological agent, 3,6-dichlorobenzo[b]thiophene-2-carboxylic acid (BT2). The ob/ob mice were treated with a low-BCAA diet or intermittent protein restriction (IPR) to reduce BCAA nutritional intake. Metformin unexpectedly inhibited the catabolism of BCAAs in obese mice, resulting in an elevation of BCAA abundance. AMP-activated protein kinase (AMPK) mediated the impact of metformin on BCAA catabolism in hepatocytes. Importantly, enhancing BCAA catabolism via a pharmacological agent BT2 significantly potentiated the glucose-lowering effect of metformin while decreasing circulating BCAA levels in ob/ob and DIO mice. Similar outcomes were achieved by a nutritional approach of reducing BCAA intake. IPR also effectively reduced the circulating BCAA abundance and enhanced metformin's glucose-lowering effect in ob/ob mice. BT2 and IPR treatments reduced the expression of fructose-1,6-bisphosphatase 1, a rate-limiting enzyme in gluconeogenesis, in the kidney but not liver, indicating the involvement of renal gluconeogenesis. Metformin self-limits its therapeutic efficacy in the treatment of type 2 diabetes by triggering the suppression of BCAA catabolism. Enhancing BCAA catabolism pharmacologically or reducing BCAA intake nutritionally potentiates the glucose-lowering effect of metformin. These data highlight the nutritional impact of protein on metformin's therapeutic efficacy and provide new strategies targeting BCAA metabolism to improve metformin's effects on the clinical outcome in diabetes.

SGLT2-inhibition increases total, LDL, and HDL cholesterol and lowers triglycerides: Meta-analyses of 60 randomized trials, overall and by dose, ethnicity, and drug type

Background and aimsSodium glucose co-transporter 2 (SGLT2)-inhibitors were developed as glucose-lowering drugs. Surprisingly, SGLT2-inhibitors also reduced risk of cardiovascular disease. The impact of SGLT2-inhibitors on lipids and lipoproteins is unclear, but an effect might contribute to the observed lower cardiovascular risk. We conducted a meta-analysis to examine this, overall and by dose, ethnicity, and drug type. MethodsPubMed, EMBASE and Web of Science were searched for randomized controlled trials examining all available SGLT2-inhibitors. Studies with available lipid measurements were included. Quantitative data synthesis was performed using random and fixed effects models. ResultsWe identified 60 randomized trials, including 147,130 individuals. Overall, using random effects models, SGLT2-inhibitor treatment increased total cholesterol by 0.09 mmol/L (95% CI: 0.06, 0.13), low-density lipoprotein (LDL) cholesterol by 0.08 mmol/L (0.05, 0.10), and high-density lipoprotein (HDL) cholesterol by 0.06 mmol/L (0.05, 0.07), while it reduced triglycerides by 0.10 mmol/L (0.06, 0.14). Fixed effects estimates were similar but with smaller effect sizes for HDL cholesterol and triglycerides. For higher SGLT2-inhibitor doses, there was a nominally higher non-significant effect on lipids and lipoproteins. In Asian compared to non-Asian populations, a slightly larger increase in HDL cholesterol and a decrease in triglycerides were observed, but with similar results for total and LDL cholesterol. Treatment effects on lipids and lipoproteins were generally robust across different SGLT2-inhibitor drugs. ConclusionIn meta-analyses, SGLT2-inhibition increased total, LDL, and HDL cholesterol and decreased triglycerides. Effect sizes varied slightly by drug dose and ethnicity but were generally robust by drug type.

Metformin Impedes Oxidation of LDL In Vitro.

Metformin is the most commonly prescribed glucose-lowering drug for the treatment of type 2 diabetes. The aim of this study was to investigate whether metformin is capable of impeding the oxidation of LDL, a crucial step in the development of endothelial dysfunction and atherosclerosis. LDL was oxidized by addition of CuCl2 in the presence of increasing concentrations of metformin. The extent of LDL oxidation was assessed by measuring lipid hydroperoxide and malondialdehyde concentrations, relative electrophoretic mobilities, and oxidation-specific immune epitopes. Cytotoxicity of oxLDL in the vascular endothelial cell line EA.hy926 was assessed using the alamarBlue viability test. Quantum chemical calculations were performed to determine free energies of reactions between metformin and radicals typical for lipid oxidation. Metformin concentration-dependently impeded the formation of lipid hydroperoxides, malondialdehyde, and oxidation-specific immune epitopes when oxidation of LDL was initiated by addition of Cu2+. The cytotoxicity of oxLDL was reduced when it was obtained under increasing concentrations of metformin. The quantum chemical calculations revealed that only the reaction of metformin with hydroxyl radicals is exergonic, whereas the reactions with hydroperoxyl radicals or superoxide radical anions are endergonic. Metformin, beside its glucose-lowering effect, might be a suitable agent to impede the development of atherosclerosis and associated CVD. This is due to its capability to impede LDL oxidation, most likely by scavenging hydroxyl radicals.

Glucose-lowering drug use in migrants and native Danes with type 2 diabetes: Disparities in combination therapy and drug types.

To examine disparities in glucose-lowering drug (GLD) usage between migrants and native Danes with type 2 diabetes (T2D). In a nationwide, register-based cross-sectional study of 253 364 individuals with prevalent T2D on December 31, 2018, we examined user prevalence during 2019 of (i) GLD combination therapies and (ii) individual GLD types. Migrants were grouped by origin (Middle East, Europe, Turkey, Former Yugoslavia, Pakistan, Sri Lanka, Somalia, Vietnam), and relative risk (RR) versus native Danes was computed using robust Poisson regression to adjust for clinical and socioeconomic characteristics. In 2019, 34.7% of native Danes received combination therapy, and prevalence was lower in most migrant groups (RR from 0.78, 95% confidence interval CI 0.71-0.85 [Somalia group] to 1.00, 95% CI 0.97-1.04 [former Yugoslavia group]). Among native Danes, the most widely used oral GLD was metformin (used by 62.1%), followed by dipeptidyl peptidase-4 inhibitors (13.3%), sodium-glucose cotransporter-2 inhibitors (11.9%) and sulphonylureas (5.2%), and user prevalence was higher in most migrant groups (RR for use of any oral GLD: 0.99, 95% CI 0.97-1.01 [Europe group] to 1.09, 95% CI 1.06-1.11 [Sri Lanka group]). Furthermore, 18.7% of native Danes used insulins and 13.3% used glucagon-like peptide-1 receptor agonists (GLP-1RAs), but use was less prevalent in migrants (RR for insulins: 0.66, 95% CI 0.62-0.71 [Sri Lanka group] to 0.94, 95% CI 0.89-0.99 [Europe group]; RR for GLP-1RAs: 0.29, 95% CI 0.22-0.39 [Somalia group] to 0.95, 95% CI 0.89-1.01 [Europe group]). Disparities in GLD types and combination therapy were evident between migrants and native Danes. Migrants were more likely to use oral GLDs and less likely to use injection-based GLDs, particularly GLP-1RAs, which may contribute to complication risk and mortality among this group.

Cardiovascular prevention with glucose-lowering drugs in type 2 diabetes: An evidence-based approach to the categories of primary and secondary prevention.

Whether to recommend specifically the glucose-lowering therapies with cardiovascular benefit only in secondary prevention, or also in patients with multiple risk factors (MRF) but without established atherosclerotic cardiovascular disease (ASCVD), is controversial across the guidelines for diabetes. We performed a meta-analysis of clinical trials with major adverse cardiovascular events (MACE) as an outcome. The definitions of ASCVD and MRF were heterogeneous across trials; nevertheless, the incidence of MACE was 2.8-fold higher in people with ASCVD in trials with sodium-glucose cotransporter 2 inhibitors (SGLT2is), and 3.9-fold in trials with glucagon-like peptide-1 receptor agonists (GLP-1 RA). Both SGLT2i and GLP-1 RA were associated with a significant reduction in the incidence of MACE in people with previous ASCVD [inverse variance-odds ratio 0.91, 95% confidence interval (0.86: 0.97) for SGLT2i, Mantel-Haenszel odds ratio 0.85, 95% confidence interval (0.81: 0.90) for GLP-1 RA], whereas no significant reduction was detected in those without; on the other hand, no significant difference in effect was found between the two groups as well. The sample of patients without ASCVD enrolled in clinical trials is insufficient to draw reliable conclusions in this population; however, even assuming the same benefit detected in people with ASCVD also in those with MRF, the number needed to treat would differ (35 for secondary, 99 for primary prevention of a MACE with a SGLT2i; 21 for secondary, 82 for primary prevention with a GLP-1 RA, respectively), given the difference in absolute cardiovascular risk at baseline. The distinction between patients with ASCVD and those without ASCVD and MRF appears therefore justified by available evidence.

Risk of first-time major cardiovascular event among individuals with newly diagnosed type 2 diabetes: data from Danish registers

Aims/hypothesisWe aimed to examine whether individuals with initial omission of glucose-lowering drug treatment (GLDT), including those achieving initial remission of type 2 diabetes, may experience a higher risk of major adverse cardiovascular events (MACE) compared with well-controlled individuals on GLDT after a new type 2 diabetes diagnosis in real-world clinical practice. Furthermore, we examined whether a higher risk could be related to lower initiation of statins and renin–angiotensin system inhibitors (RASi).MethodsIn this cohort study, we used Danish registers to identify individuals with a first measured HbA1c between 48 and 57 mmol/mol (6.5–7.4%) from 2014 to 2020. Six months later, we divided participants into four groups according to GLDT and achieved HbA1c (<48 vs ≥48 mmol/mol [6.5%]): well-controlled and poorly controlled on GLDT; remission and persistent type 2 diabetes not on GLDT. We reported how much the standardised 5 year risk of MACE could be reduced for each group if initiation of statins and RASi was the same as in the well-controlled group on GLDT.ResultsWe included 14,221 individuals. Compared with well-controlled participants on GLDT, the 5 year standardised risk of MACE was higher in the three other exposure groups: by 3.3% (95% CI 1.6, 5.1) in the persistent type 2 diabetes group not on GLDT; 2.0% (95% CI 0.4, 3.7) in the remission group not on GLDT; and 3.5% (95% CI 1.3, 5.7) in the poorly controlled group on GLDT. Fewer individuals not on GLDT initiated statins and RASi compared with individuals on GLDT. If initiation of statins and RASi had been the same as in the well-controlled group on GLDT, participants not on GLDT could have reduced their risk of MACE by 2.1% (95% CI 1.2, 2.9) in the persistent type 2 diabetes group and by 1.1% (95% CI 0.4, 1.9) in the remission group.Conclusions/interpretationCompared with well-controlled individuals on GLDT, individuals not on initial GLDT had a higher 5 year risk of MACE, even among those achieving remission of type 2 diabetes. This may be related to lower use of statins and RASi.Graphical

Bi-Directional Interactions between Glucose-Lowering Medications and Gut Microbiome in Patients with Type 2 Diabetes Mellitus: A Systematic Review.

Background: Although common drugs for treating type 2 diabetes (T2D) are widely used, their therapeutic effects vary greatly. The interaction between the gut microbiome and glucose-lowering drugs is one of the main contributors to the variability in T2D progression and response to therapy. On the one hand, glucose-lowering drugs can alter gut microbiome components. On the other hand, specific gut microbiota can influence glycemic control as the therapeutic effects of these drugs. Therefore, this systematic review assesses the bi-directional relationships between common glucose-lowering drugs and gut microbiome profiles. Methods: A systematic search of Embase, Web of Science, PubMed, and Google Scholar databases was performed. Observational studies and randomised controlled trials (RCTs), published from inception to July 2023, comprising T2D patients and investigating bi-directional interactions between glucose-lowering drugs and gut microbiome, were included. Results: Summarised findings indicated that glucose-lowering drugs could increase metabolic-healthy promoting taxa (e.g., Bifidobacterium) and decrease harmful taxa (e.g., Bacteroides and Intestinibacter). Our findings also showed a significantly different abundance of gut microbiome taxa (e.g., Enterococcus faecium (i.e., E. faecium)) in T2D patients with poor compared to optimal glycemic control. Conclusions: This review provides evidence for glucose-lowering drug and gut microbiome interactions, highlighting the potential of gut microbiome modulators as co-adjuvants for T2D treatment.

Comparative effectiveness of second line glucose lowering drug treatments using real world data: emulation of a target trial

ObjectiveTo build on the recently completed GRADE (Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study) randomised trial examining the comparative effectiveness of second line glucose lowering drugs in achieving...

Association of Met420del Variant of Metformin Transporter Gene SLC22A1 with Metformin Treatment Response in Ethiopian Patients with Type 2 Diabetes.

This study aimed to evaluate whether the M420del variants of SLC22A1 (rs72552763) is associated with metformin treatment response in Ethiopian patients with type 2 diabetes mellitus (T2DM). A prospective observational cohort study was conducted on 86 patients with T2DM who had been receiving metformin monotherapy for <1 year. Patients showing ≥0.5% reduction in HbA1c levels from baseline within 3 months and remained low for at least another 3 months were defined as responders while those patients with <0.5% reduction in HbA1c levels and/or those whom started a new class of glucose-lowering drug(s) because of unsatisfactory reduction were defined as non-responders. In addition, good glycemic control was observed when HbA1c ≤7.0%, and the above values were regarded as poor. Genotyping of rs72552763 SNP was performed using TaqMan® Drug Metabolism Enzyme Genotyping Assay and its association with metformin response and glycemic control were assessed by measuring the change in HbA1c and fasting blood glucose levels using Chi-square, logistic regression and Mann-Whitney U-test. Statistical significance was set at p <0.05. The minor allele frequency of the rs72552763 SNP of SLC22A1 was 9.3%. Metformin response was significantly higher in deletion_GAT (del_G) genotypes as compared to the wild-type GAT_GAT (G_G) genotypes. Furthermore, a significantly lower median treatment HbA1 level was found in del_G genotypes as compared to G_G genotypes. However, the association of rs72552763 with metformin response was not replicated at the allele level. In contrast, the minor del_allele was significantly associated with good glycemic control compared to the G_allele, though not replicated at del_G genotypes level. This study demonstrated that metformin response was significantly higher in study participants with a heterozygous carrier of M420del variants of SLC22A1 as compared to the wild-type G_G genotypes after 3 months of treatment.

Real-world evidence on health-related quality of life in patients with type 2 diabetes mellitus using sulphonylureas: An analysis of the Joint Asia Diabetes Evaluation (JADE) Register

AimsTo describe health-related quality of life (HRQoL) and identify associated factors in patients with type 2 diabetes mellitus (T2DM) treated with oral glucose-lowering drugs (OGLDs). MethodsThis retrospective, cross-sectional analysis included adults with T2DM from 11 Asian countries/regions prospectively enrolled in the Joint Asian Diabetes Evaluation (JADE) Register (2007–2019) with available EuroQol-5D (EQ-5D-3L) data. ResultsOf 47,895 included patients, 42,813 were treated with OGLDs + lifestyle modifications (LSM) and 5,082 with LSM only. Among those treated with OGLDs, 60% received sulphonylureas (SUs), of whom 47% received gliclazide. The OGLD + LSM group had a lower mean EQ-5D-3L index score than the LSM-only group (p < 0.001). The most affected EQ-5D-3L dimensions in OGLD + LSM-treated patients were pain/discomfort (26.2%) and anxiety/depression (22.6%). On multivariate analysis, good HRQoL was positively associated with male sex, education level, balanced diet and regular exercise, and negatively with complications/comorbidities, self-reported hypoglycaemia, smoking, HbA1c, age, body mass index and disease duration. Patients receiving gliclazide vs non-gliclazide SUs had lower HbA1c and better HRQoL in all dimensions (p < 0.001). ConclusionsDemographic, physical and psychosocial-behavioural factors were associated with HRQoL in patients with T2DM. Our real-world data add to previous evidence that gliclazide is an effective OGLD, with most treated patients reporting good HRQoL.A plain language summary of this manuscript is available here.

Hepatotropc effects of glucose-lowering drugs: non-alcoholic fatty liver disease in focus

Hepatotropc effects of glucose-lowering drugs: non-alcoholic fatty liver disease in focus

Add-On Therapy of Dapagliflozin to Metformin in Patients with Diabetes Mellitus Type-2; Efficacy and Renal Safety

Objective: To study efficacy of Dapagliflozin in treatment of diabetes mellitus type-2. Study Design: Quasi-experimental study. Place and Duration of Study: Medical unit, Benazir Bhutto Shaheed Hospital, Rawalpindi Pakistan from Jan to Dec 2019. Patients &amp; methods: Patients taking Dapagliflozin in combination with Metformin (MET+DAPA) (n=45) were compared to those taking other glucose lowering agent in combination with Metformin (MET+ other drug) (n=45) for the control of diabetes mellitus type-II. Efficacy of treatment was assessed by the level of glycosylated hemoglobin HbA1c, and renal safety assessed by serum creatinine level done at 6 and 12 months of treatment. Results: Total 90 cases were studied including 60% male and 40% female cases with mean age 50.8±7.4 years. Patients taking Dapagliflozin + Metformin (n=45), and others taking Metformin+ other glucose lowering drug (n=45) were having mean values of BMI 32.8±5.9 kg/m2 &amp; 33.4±7.2 kg/m2, HbA1c 8.4±1.2% &amp; 9.1±1.6 % and blood urea nitrogen 6.7±1.4 &amp; 6.5±1.8 mmol/L respectively. After 12 months treatment mean HbA1c level was reduced from 8.7 ± 1.4% to 6.6 ± 0.3%, BMI reduced significantly and no detrimental effects reported on renal function. Conclusion: Patients with type-II diabetes mellitus taking Dapagliflozin in combination with Metformin showed good glycemic control and renal safety.

Residual cardiovascular risk, use of standard care treatments, and achievement of treatment goals in patients with cardiovascular disease

BackgroundResidual risk management in patients with previous cardiovascular disease (CVD) is a relevant issue. Objectives: 1) to assess the residual risk of patients with CVD using the new scores developed to predict recurrent CVD events (SMART score/SMART-REACH model); 2) to determine the use of therapies with cardiovascular benefit and the achievement of therapeutic goals in patients with very high residual risk. MethodsA multicenter, descriptive, cross-sectional study was performed. Individuals over 18 years of age with CVD were included consecutively. The 10-year risk of recurrent events was estimated using the SMART score and the SMART-REACH model. A value ≥ 30% was considered “very high risk”. ResultsIn total, 296 patients (mean age 68.2 ± 9.4 years, 75.7% men) were included. Globally, 32.43% and 64.53% of the population was classified as very high risk by the SMART score and the SMART-REACH model, respectively. Among patients classified as very high risk by the SMART score, 45.7% and 33.3% were treated with high-intensity statins and reached the goal of LDL-C <55 mg/dL, respectively. The results were similar when evaluating very high patients according to the SMART-REACH model (high-intensity statins: 59.7%; LDL-C <55 mg/dL: 43.9%). Few very high-risk patients with diabetes were receiving glucose-lowering drugs with demonstrated cardiovascular benefit. ConclusionIn this secondary prevention population, the residual risk was considerable. Underutilization of standard care treatments and failure to achieve therapeutic goals were evident even in subjects with very high residual risk.

Blood pressure-lowering effects of SGLT2 inhibitors and GLP-1 receptor agonists for preventing of cardiovascular events and death in type 2 diabetes: a systematic review and meta-analysis.

To investigate the lowering BP effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) on the risk of major cardiovascular event stratified by glucose-lowering drugs, baseline BP, glycated hemoglobin (HbA1c), and history of cardiovascular disease in patients with type 2 diabetes. We performed a systematic review of the MEDLINE and EMBASE databases search up to December 31, 2022, (PROSPERO, CRD42023400899) to identify all large-scale cardiovascular outcomes (CVO) trials of SGLT2i and GLP-1 RAs in which more than 1,000 patient-years of follow-up in each randomized group. Outcomes included all-cause mortality, major adverse cardiovascular event (MACE) and its component (cardiovascular death, myocardial infarction [MI], and stroke), heart failure, and renal failure. A random-effects meta-analyses were used to pool the estimates. Eighteen CVOTs (ten for SGLT2i and eight for GLP-1 RAs) with 127,606 patients with type 2 diabetes were included. Over 2.5years median follow-up, the average reduction of systolic BP was 2.2mmHg (mean difference [MD] - 2.2; 95% CI - 2.7 to - 1.7) with more important reduction (Pinteraction = 0.001) with SGLT2 inhibitors (- 2.9; - 3.4 to - 2.5) than with GLP-1 RAs (- 1.4; - 1.8 to - 1). With SGLT2i, every 5-mmHg reduction in systolic BP was associated with a significantly lower risk of mortality (hazard ratio[HR], 0.77; 95% CI 0.65-0.90), MACE (HR 0.81 [0.74-0.89]), cardiovascular death (HR 0.72 [0.59-0.88]), MI (HR 0.82 [0.71-0.95]), heart failure (HR 0.49 [0.42-0.57]), and renal failure (HR 0.46 [0.38-0.55]), while the association was not significant for stroke (HR 0.91 [0.69-1.19]). The corresponding effects for every 5-mmHg reduction in SBP with GLP-1 RAs were 0.65 (0.51-0.84) for all-cause mortality, 0.65 (0.56-0.76) for MACE, 0.62 (0.45-0.85) for CV death, 0.71 (0.52-0.76) for MI, 0.49 (0.35-0.69) for stroke, and 0.49 (0.35-0.66) for renal failure, while the association was not significant for heart failure (HR 0.82 [0.63-1.08]). In patients with type 2 diabetes, the hypotensive effects of SGLT2i and GLP-1 RAs were significantly associated with a reduction in mortality and cardiorenal events. These findings suggest that the lowering BP effect could be seen as an additive indicator of cardiovascular protection by SGLT2i and GLP-1 RAs drugs.

Sodium-Glucose Cotransporter-2 Inhibitors After Acute Myocardial Infarction in Patients With Type 2 Diabetes: A Population-Based Investigation.

Background Whether the early use of sodium-glucose cotransporter-2 (SGLT2) inhibitors have cardioprotective effects following acute myocardial infarction is unknown. Thus, we aimed to evaluate the association between the early initiation of SGLT2 inhibitors and cardiac event rates in patients with diabetes with acute myocardial infarction undergoing percutaneous coronary intervention. Methods and Results Based on the National Health Insurance claims data in South Korea, patients who received percutaneous coronary intervention for acute myocardial infarction between 2014 and 2018 were analyzed. Patients given SGLT2 inhibitors or other glucose-lowering drugs were matched based on a propensity score. The primary end point was a composite of all-cause mortality and hospitalizations for heart failure. Major adverse cardiac events (a composite of all-cause death, nonfatal myocardial infarction, and ischemic stroke) were compared as the secondary end point. After 1:2 propensity score matching, the SGLT2 inhibitors group (938 patients) and the no use of SGLT2 inhibitors group (1876 patients) were compared. During a median follow-up of 2.1 years, the early use of SGLT2 inhibitors was associated with lower risks of both the primary end point (9.8% versus 13.9%; adjusted hazard ratio [HR], 0.68 [95% CI, 0.54-0.87]; P=0.002) and secondary end point (9.1% versus 11.6%; adjusted HR, 0.77 [95% CI, 0.60-0.99]; P=0.04). All-cause mortality and hospitalizations for heart failure were also significantly lower in early users of SGLT2 inhibitors. Conclusions The early use of SGLT2 inhibitors in patients with diabetes treated with percutaneous coronary intervention for acute myocardial infarction was associated with a significantly lower risk of cardiovascular events, including all-cause mortality, hospitalizations for heart failure, and major adverse cardiac events.