Reduction In HbA1c Levels Research Articles

Partnering for Better Health: Using Continuous Glucose Monitoring and Clinical Pharmacist Collaboration to Improve Glycemic Control in Underserved Patients With Type 2 Diabetes

PurposeThe purpose of this study was to examine the effect of initiating use of a continuous glucose monitor (CGM) in patients being treated for type 2 diabetes mellitus, specifically those who face barriers to obtaining this device because of its cost. MethodsThis retrospective medical record review compared diabetes control of patients before and after use of a CGM device within a single primary care office. Patient medical records were reviewed 18 months after initial CGM was provided, and only those who received a CGM directly from the clinic were included in the review. Statistical analysis comparing the difference in mean baseline glycosylated hemoglobin (HbA1c) level with the first HbA1c level after CGM placement was completed using the paired t test for the primary outcome. FindingsA total of 41 patients who obtained at least 1 CGM reader and a minimum of a 30-day supply of sensors from the clinic were included in the review. The primary outcome resulted in a significant reduction in the mean (SD) first HbA1c level after CGM placements of −1.9% (2.5%) (P < .001) with a total of 10 and 22 patients with an HbA1c level <7% and 8%, respectively. This mean (SD) reduction in HbA1c level was also seen in both insulin-treated patients (−1.8% [2.8%], n = 30) and non–insulin-treated patients (−2% [2.8%], n=11). The largest reduction in the first HbA1c level after CGM placement was seen in those patients provided a CGM along with collaborative care with a clinical pharmacist. These patients saw a mean (SD) decrease of −2.5% [2.7%] (n = 26) in their HbA1c level with a mean (SD) decrease of −0.8% (1.6%) (n = 15) for those not comanaged by the clinical pharmacist. ImplicationsThe results of this study suggest that the use of CGM in the underserved population can lead to a significant improvement in glycemic control in patients with diabetes, regardless of treatment therapies used. Involving a multidisciplinary team in diabetes management, including clinical pharmacists, may further improve outcomes. Access to these devices in the underserved population may be crucial in reducing the risk of developing complications related to uncontrolled diabetes.

Once-weekly insulin icodec as novel treatment for type 2 diabetes mellitus: A systematic review and meta-analysis of randomized clinical trials

AimsThe primary objective of this investigation is to examine the efficacy and safety of insulin icodec when compared to regular basal insulin for the management of type 2 diabetes mellitus (T2DM). MethodsA comprehensive search was conducted on the Cochrane Library, Scopus, ClinicalTrials.gov, and Medline databases up until August 19th, 2023. This review incorporates literature that examines the comparison between insulin icodec and basal insulin. The risk of bias was assessed by using RoB v2 tool from Cochrane Collaborations. We employed random-effect models to analyze the mean difference (MD) and odds ratio (OR) for presentation of the outcomes. ResultsA total of nine trials with 3,963 participants were incorporated. Five included trials had “low-risk” of bias, whereas the remaining four trials had “some-concern” risk of bias due to protocol deviations from intended intervention. The results of our meta-analysis showed no significant difference in the reduction of HbA1c levels between insulin icodec and regular basal insulin (MD −0.11 %; 95 %CI: −0.23, 0.01, p = 0.08, I2 = 91 %). The fasting plasma glucose (FPG) and body weight change from baseline also did not differ significantly between two groups. Meanwhile, the total adverse events (TAEs) were shown to be higher in the insulin icodec; however, the serious AEs (SAEs) and clinically significant hypoglycemia did not differ significantly between insulin icodec and these active controls. ConclusionsThis study suggests similar efficacy and safety between insulin icodec and regular basal insulin. Further clinical trials are still needed to confirm the results of our study.Registration details: CRD42023453635.

The effect of nurse-led telephone-based interventions on glycosylated hemoglobin levels in people with type 2 diabetes: A meta-analysis.

Telenursing interventions can contribute to achieving optimal glycemic control. This meta-analysis aimed to determine the effect of nurse-led telephone-based interventions on glycosylated hemoglobin (HbA1c) levels in people with type 2 diabetes. We searched electronic databases for studies published in English up to January 2023. This study was conducted in accordance with the PRISMA 2020 checklist. The intervention effects were pooled using a random-effects model. Two authors independently assessed the risk of bias using the Cochrane Collaboration tool. Eight studies involving 1179 people with type 2 diabetes were included in this study. Interventions were performed for 15-30 min and 5-16 calls. There was no evidence of a significant publication bias. The evaluation of meta-analysis data showed that nurse-led telephone-based interventions significantly reduced HbA1c levels in people with type 2 diabetes (mean difference = -0.53, 95% Confidence Interval [-0.89, -0.17], p = .003). Nurse-led telephone-based interventions focused on reducing glycosylated hemoglobin levels in people with type 2 diabetes can be used as an effective intervention to achieve glycemic control. We recommend holding an average of 15-25 min interviews once or twice a week.

Effect of tirzepatide on glycaemic control and weight loss compared with other glucagon-like peptide-1 receptor agonists in Japanese patients with type 2 diabetes mellitus.

To compare the therapeutic effects of glucose-dependent insulinotropic polypeptide (GIP)/ glucagon-like peptide-1 receptor agonists (GLP-1RAs) or GLP-1RAs in Japanese patients with type 2 diabetes (T2D). We systematically searched PubMed, MEDLINE, EMBASE, and the Cochrane Library up to July 2023. Randomized controlled trials (RCTs) that compared GLP-1RAs or GIP/GLP-1RAs in Japanese patients with T2D were selected. A network meta-analysis was conducted to indirectly compare the treatments, focusing on efficacy in reducing glycated haemoglobin (HbA1c) levels and body weight (BW). A total of 18 RCTs were included in this analysis. Tirzepatide 15 mg showed the most significant reduction in HbA1c levels and BW compared with subcutaneous semaglutide 1.0 mg and oral semaglutide 14 mg (HbA1c: mean difference [95% confidence interval] -0.52 [-0.96; -0.08] and - 1.23 [-1.64; -0.81]; BW: -5.07 [-8.28; -1.86] and -6.84 [-8.97; -4.71], respectively). Subcutaneous semaglutide showed a superior reduction in HbA1c compared with oral semaglutide. Both subcutaneous and oral semaglutide were more effective than conventional GLP-1RAs, such as dulaglutide, liraglutide and lixisenatide. Among Japanese patients with T2D, tirzepatide showed the greatest effectiveness in reducing HbA1c levels and inducing weight loss. The study provides evidence to guide GLP-1RA treatment strategies in Japanese patients with T2D.

Personalized glucose-lowering effect of chiglitazar in type 2 diabetes

Chiglitazar (carfloglitazar) is a peroxisome proliferator-activated receptor pan-agonist presenting non-inferior glucose-lowering efficacy with sitagliptin in patients with type 2 diabetes. To delineate the subgroup of patients with greater benefit from chiglitazar, we conducted a machine learning-based post-hoc analysis in two randomized controlled trials. We established a character phenomap based on 13 variables and estimated HbA1c decline to the effects of chiglitazar in reference to sitagliptin. Out of 1,069 patients, 63.3% were found to have greater reduction in HbA1c levels with chiglitazar, while 36.7% showed greater reduction with sitagliptin. This distinction in treatment response was statistically significant between groups (pinteraction<0.001). To identify patients who would gain the most glycemic control benefit from chiglitazar, we developed a machine learning model, ML-PANPPAR, which demonstrated robust performance using sex, BMI, HbA1c, HDL, and fasting insulin. The phenomapping-derived tool successfully identified chiglitazar responders and enabled personalized drug allocation in patients with drug-naïve diabetes.

THU244 Clinical Factors Affecting Dapagliflozin Response For Glycemic Control And Body Weight Reduction: Post-hoc Analysis Of BEYOND Study

Abstract Disclosure: K. Ahn: None. J. Ji Eun: None. J. In-Kyung: None. Background: Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, ameliorates hyperglycemia and obesity by inhibiting renal glucose reabsorption. However, significant heterogeneity exists in glucose-lowering efficacy and the magnitude of the weight loss among patients with type 2 diabetes. Herein, we aimed to evaluate the clinical factors affecting response to dapagliflozin treatment. Methods: We performed a post-hoc analysis of the BEYOND (Effects of Dapagliflozin Compared with Glimepiride on Body Composition in Patients with Type 2 Diabetes Inadequately Controlled with Metformin) randomized, double-blind, parallel-group trial. Patients were randomly assigned (1:1) to receive the addition of either dapagliflozin 10 mg per day or glimepiride 1∼2 mg per day to background metformin therapy for 52 weeks. Changes in HbA1c and body weight from baseline during the observation period were assessed for all patients. Responder to dapagliflozin was defined by &amp;gt;1% reduction in A1c and &amp;gt;3% reduction in body weight at week 52. Then, we classified the total subjects into 4 groups: non-responder of both A1c reduction and body weight reduction, responders of A1c reduction but non-responder of body weight reduction, non-responder of A1c reduction but responders of body weight reduction, and responders of both A1c reduction and body weight reduction. Results: Among 56 patients in a dapagliflozin arm, 55.4% (N = 31) and 57.1% (N = 32) experienced clinical responses as indicated by reductions in HbA1c and in body weight reduction, respectively. Younger age and higher HbA1c level at baseline were significantly associated with a greater HbA1c reduction, and a higher estimated glomerular filtration rate (eGFR) was significantly associated with a greater body weight reduction. However, there was no association between the change in HbA1c and the change in body weight (r = −0.133, P = 0.328). Responders of both A1c reduction and body weight reduction were most common (32.1%), non-responders of A1c reduction but responders of body weight reduction were second-most (25.0%), responders of A1c reduction but non-responders of body weight reduction were 23.2%, and non-responders of both A1c reduction and body weight reduction were 19.6%. Subjects with higher fasting plasma glucose (FPG) and HbA1c in addition to lower eGFR at baseline had a greater reduction in HbA1c, but less reduction in body weight. Conversely, those with lower FPG and HbA1c in addition to higher eGFR at baseline had a greater reduction in body weight, but less reduction in HbA1c level. Conclusion: Patients with type 2 diabetes actually exhibit a heterogeneous response to dapagliflozin treatment. Glucose-lowering efficacy of dapagliflozin was associated with worse baseline glycemic status, and body weight reduction was associated with baseline higher eGFR. Presentation: Thursday, June 15, 2023

BEYOND 2 years: durability of metabolic benefits by simplification of complex insulin regimens in type 2 diabetes

PurposeTo assess the magnitude and durability of the metabolic benefits by simplification of complex insulin treatments in patients with type 2 diabetes inadequately controlled by a full basal-bolus insulin regimen. Herein we report the results of the scheduled 2-year extension of the BEYOND trial.MethodsOriginally, 305 participants with inadequate glycemic control (HbA1c > 7.5%) were randomly assigned to intensification of basal-bolus insulin regimen (n = 101), to a fixed-ratio combination (basal insulin + GLP-1RA, n = 102), or to an association of basal insulin plus an SGLT-2 inhibitor (gliflo-combo, n = 102). The primary efficacy outcome was change from baseline in HbA1c at 24 months assessed by an intention-to-treat analysis. A per-protocol analysis was also performed.ResultsFifty-five percent of patients completed the study in the two comparison arms. Compared with patients randomized to basal-bolus, patients of the other groups experienced non statistically different reductions in HbA1c level according to either an intention-to-treat analysis (−0.8 ± 1.1%, −0.7 ± 1.1%, and −1.3 ± 1.1%, mean ± SD, fixed-ratio, gliflo-combo and basal bolus, respectively) or per-protocol analysis (−1.2 ± 1.0%, −1.2 ± 1.1%, and −1.3 ± 1.0%, respectively). The final HbA1c level (per protocol) was 7.2 ± 0.8%, 7.3 ± 0.9%, and 7.5 ± 0.9%, respectively (P = NS). Treatment satisfaction (DTSQ) increased in both exchange groups, whereas the proportion of patients with hypoglycemia was lower.ConclusionSimplification of complex insulin regimen may be a durable option in at least one-half of patients with type 2 diabetes.Clinical trial registrationClinical trial registration no. NCT04196231, clinicaltrials.gov.

Salsalate: a pleotropic anti-inflammatory drug in the treatment of diabetes, obesity, and metabolic diseases.

Type two Diabetes Mellitus (T2DM) is a rising epidemic. Available therapeutic strategies have provided glycaemic control via HbA1c reduction but fail to provide clinically meaningful reduction in microvascular and macrovascular (cardiac, renal, ophthalmological, and neurological) complications. Inflammation is strongly linked to the pathogenesis of T2DM. Underlying inflammatory mechanisms include oxidative stress, endoplasmic reticulum stress amyloid deposition in the pancreas, lipotoxicity, and glucotoxicity. Molecular signalling mechanisms in chronic inflammation linked to obesity and diabetes include JANK, NF-kB, and AMPK pathways. These activated pathways lead to a production of various inflammatory cytokines, such as Interleukin (IL-6), tumor necrosis factor (TNF)-alpha, and C-reactive protein (CRP), which create a chronic low-grade inflammation and ultimately dysregulation of glucose homeostasis in the liver, skeletal muscle, and smooth muscle. Anti-inflammatory agents are being tested as anti-diabetic agents such as the IL-1b antagonist, Anakinra, the IL-1b inhibitor, Canakinuma, the IL-6 antagonists such as Tocilizumab, Rapamycin (Everolimus), and the IKK-beta kinase inhibitor, Salsalate. Salsalate is a century old safe anti-inflammatory drug used in the treatment of arthritis. Long-term safety and efficacy of Salsalate in the treatment of T2DM have been evaluated, which showed improved fasting plasma glucose and reduced HbA1C levels as well as reduced pro-inflammatory markers in T2DM patients. Current publication summarizes the literature review of pathophysiology of role of inflammation in T2DM and clinical efficacy and safety of Salsalate in the treatment of T2DM.

Efficacy of metformin targets on cardiometabolic health in the general population and non-diabetic individuals: a Mendelian randomization study

Metformin shows beneficial effects on cardiometabolic health in diabetic individuals. However, the beneficial effects in the general population, especially in non-diabetic individuals are unclear. We aim to estimate the effects of perturbation of seven metformin targets on cardiometabolic health using Mendelian randomization (MR). Genetic variants close to metformin-targeted genes associated with expression of the corresponding genes and glycated haemoglobin (HbA1c) level were used to proxy therapeutic effects of seven metformin-related drug targets. Eight cardiometabolic phenotypes under metformin trials were selected as outcomes (average N=466,947). MR estimates representing the weighted average effects of the seven effects of metformin targets on the eight outcomes were generated. One-sample MR was applied to estimate the averaged and target-specific effects in 338,425 non-diabetic individuals in UK Biobank. Genetically proxied averaged effects of five metformin targets, equivalent to a 0.62% reduction of HbA1c level, was associated with 37.8% lower risk of coronary artery disease (CAD) (odds ratio [OR]=0.62, 95% confidence interval [CI]=0.46-0.84), lower levels of body mass index (BMI) (β=-0.22, 95% CI=-0.35 to-0.09), systolic blood pressure (SBP) (β=-0.19, 95% CI=-0.28 to-0.09) and diastolic blood pressure (DBP) levels (β=-0.29, 95% CI=-0.39 to-0.19). One-sample MR suggested that the seven metformin targets showed averaged and target-specific beneficial effects on BMI, SBP and DBP in non-diabetic individuals. This study showed that perturbation of seven metformin targets has beneficial effects on BMI and blood pressure in non-diabetic individuals. Clinical trials are needed to investigate whether similar effects can be achieved with metformin medications. Funding information is provided in the Acknowledgements.

The Effects of Mindfulness on Glycemic Control in People with Diabetes: An Overview of Systematic Reviews and Meta-Analyses.

Background: Previous research has demonstrated the effectiveness of mindfulness interventions in improving glycemic control. By enhancing attention control, emotion regulation, and self-awareness, mindfulness shows promise in managing the lifestyle factors associated with cardiovascular disease risk. However, the impact of mindfulness on glycemic control in people with diabetes remains unclear. This overview aims to summarize the current evidence of the impact of mindfulness interventions on glycemic control in people with diabetes and propose suggestions for future research. Methods: The author searched electronic databases (PubMed/MEDLINE, Embase, and Cochrane Library) to identify relevant systematic reviews and meta-analyses. The current evidence regarding the effects of mindfulness on glycemic control in people with diabetes was summarized. Results: This review evaluated a total of five systematic reviews and meta-analyses of randomized controlled trials (RCTs). Mindfulness interventions show potential for improving glycemic control as measured by hemoglobin A1c (HbA1c) levels, as well as reducing stress, depression, and anxiety in people with diabetes. Four out of five systematic reviews and meta-analyses reported a significant reduction in HbA1c levels by approximately 0.3%. However, the available studies lacked adequate description of key characteristics of study subjects, such as body mass index, medication, and disease conditions, which are essential for assessing the impact of mindfulness on glycemic control. Moreover, there was significant heterogeneity in the intervention methods employed across the included RCTs. Conclusions: Mindfulness interventions are effective in improving glycemic control in people with type 2 diabetes. However, the overall quality of the reviewed studies raises uncertainty regarding the effectiveness of mindfulness as a treatment for people with diabetes. Further research is necessary to elucidate the biological effects of mindfulness on physiological, neurological, and endocrinological functions in humans.

Efficacy of Glargine Insulin Compared with Neutral Protamine Hagedorn Insulin in Patients with Type 2 Diabetes not Controlled with Oral Hypoglycemics: A Cohort Study

Objective: To compare the efficacy of Glargine Insulin with Neutral Protamine Hagedorn (NPH) Insulin in patients with uncontrolled type 2 diabetes with oral hypoglycemic.&#x0D; Study Design: Prospective cohort study.&#x0D; Place and Duration of the Study: Railway Hospital, Rawalpindi Pakistan, from Nov 2020 to Jul 2021.&#x0D; Methodology: All patients aged 30-70 years of either gender, presented with uncontrolled diabetes mellitus on oral hypoglycemic for ≥1 year were enrolled. Patients were divided into Insulin Glargine and injection NPH subcutaneously by lottery method. In both groups, patients were compared for a reduction in HbA1c level after three months of treatment with Insulin. The efficacy was achieved after three months based on a&gt;1% HbA1c level reduction compared to baseline HbA1c.&#x0D; Results: The efficacy of Glargine Insulin was found to be significantly higher, 66(66%), as compared to NPH Insulin, 43(43%) (p-value = 0.002). After adjusting for all other covariates, the efficacy of Glargine Insulin was 3.81 times higher as compared to NPH Insulin (aOR 3.81, 95% CI 1.93-7052). Furthermore, efficacy was 6.95 times higher in patients with ≤25 kg/m2 BMI (aOR 6.95, 95% CI 3.16-15.30), 2.52 times higher in patients with ≤16 years of type 2 diabetes (aOR 2.52, 95% CI 1.30-4.87), 2.77 times higher in patients living in urban areas (aOR 2.77, 95% CI 1.43-5.36).&#x0D; Conclusion: The efficacy of Glargine Insulin was found to be considerably higher than NPH Insulin in patients with type 2 diabetes not controlled with oral hypoglycemia.Keywords: Efficacy, Glargine insulin, NPH insulin, Type 2 diabetes.

The Expanding Role of Pharmacists in Patient Centered Diabetes Care Impacts on Management and Outcomes

The role of pharmacists in diabetes care has evolved significantly, shifting from traditional dispensing to comprehensive patient-centred management. This article explores the expanding responsibilities of pharmacists in diabetes management, highlighting their impact on clinical outcomes, economic benefits, and future directions. By providing Medication Therapy Management (MTM), pharmacists optimize medication regimens, improve medication adherence, and educate patients on lifestyle modifications, leading to enhanced glycemic control and reduced HbA1c levels. Collaborative practices with healthcare teams help prevent complications and decrease hospitalizations, demonstrating the value of integrated care. Economic analyses reveal substantial cost reductions in diabetes-related healthcare due to pharmacist interventions benefiting patients and healthcare systems. However, barriers still need to be addressed, including regulatory limitations and public awareness issues, which hinder the full realization of pharmacists’ potential in chronic disease management. The future of diabetes care is promising, with advancements in telehealth and technology paving the way for increased pharmacist involvement. Additionally, the expansion of prescribing rights may enhance the pharmacist’s role in medication management, ensuring timely and effective interventions. Addressing these challenges will be crucial for integrating pharmacists into multidisciplinary teams and optimizing diabetes care. Overall, the involvement of pharmacists is essential for delivering comprehensive and effective diabetes management, improving health outcomes, and reducing healthcare costs.

Digital Interventions in Type 2 Diabetes Mellitus

Introduction: Type 2 diabetes mellitus (T2DM) is a highly prevalent chronic disease with an increasing mortality rate over the last decade. Diabetes self-management education (DSME) programs have been reported as essential to improve survival; however, patient adherence rates are very low. Therefore, digital devices have been created to deliver DSME at a distance and enhance program attendance. This study aims to assess the effects of digitally delivered DSME programs on the glycosylated hemoglobin (HbA1C) of patients with prediabetes and T2DM. Methods: We researched PUBMED databases for randomized controlled trials (RCT) and observational studies (OS) published between 2012-2022 in English, Portuguese, or Spanish. The selected articles tested digital DSME interventions against treatment as usual (TAU) on adults (&gt;18 years) previously diagnosed with T2DM or prediabetes. The result was measured by determining the HbA1c levels. Results: Out of 261 articles, 14 RCTs were selected based on eligibility criteria. Digital DSME technologies have different objectives, including monitoring glycemic fluctuation, insulin titration, nutritional guidance, sleeping assessment, enhancement of physical activity, control of comorbidities, relevant task notifications, personalized treatment recommendations, educational content, and patient/medical staff remote interaction. Some of the technologies combined machine learning techniques for different functions, including detecting adverse glycemic events, physical activity, and blood pressure, among others. Although the level of adherence varied among the various trials, 4 of the 14 RCTs analyzed reported a significant reduction of HbA1c levels using these digital devices compared to TAU. Discussion: Programs providing digital DSME education is a potentially cost-effective tool to improve diabetes care worldwide by overcoming distance barriers, facilitating physician-patient communication, and reducing HbA1c levels. Future improvements in implementing these technologies could enhance user compliance and contribute effectively to diabetes management.

Assessing the Effectiveness of mHealth Interventions for Diabetes and Hypertension Management in Africa: Systematic Review and Meta-Analysis.

Mobile health (mHealth) interventions are effective in improving chronic disease management, mainly in high-income countries. However, less is known about the efficacy of mHealth interventions for the reduction of cardiovascular risk factors, including for hypertension and diabetes, which are rapidly increasing in low- and middle-income countries. This study aimed to assess the efficacy of mHealth interventions for diabetes and hypertension management in Africa. We searched PubMed, Cochrane Library, Google Scholar, African Journals Online, and Web of Science for relevant studies published from inception to July 2022. The main outcomes of interest were changes in hemoglobin A1c (HbA1c), systolic blood pressure, and diastolic blood pressure. The random or fixed effect model was used for the meta-analysis, and the I2 statistic was used to gauge study heterogeneity. Z tests and P values were used to evaluate the effect of mHealth interventions on HbA1c and blood pressure levels. This review included 7 studies (randomized controlled trials) with a total of 2249 participants. Two studies assessed the effect of mHealth on glycemic control, and 5 studies assessed the effect of mHealth on blood pressure control. The use of mHealth interventions was not associated with significant reductions in HbA1c levels (weighted mean difference [WMD] 0.20, 95% CI -0.40 to 0.80; P=.51) among patients with diabetes and systolic blood pressure (WMD -1.39, 95% CI -4.46 to 1.68; P=.37) and diastolic blood pressure (WMD 0.36, 95% CI -1.37 to 2.05; P=.69) among patients with hypertension. After conducting sensitivity analyses using the leave-one-out method, the Kingue et al study had an impact on the intervention, resulting in a 2 mm Hg reduction in systolic blood pressure (WMD -2.22, 95% CI -3.94 to -0.60; P=.01) but was nonsignificant for diastolic blood pressure and HbA1c levels after omitting the study. Our review provided no conclusive evidence for the effectiveness of mHealth interventions in reducing blood pressure and glycemic control in Africa among persons with diabetes and hypertension. To confirm these findings, larger randomized controlled trials are required.

The sGC Activator Runcaciguat Has Kidney Protective Effects and Prevents a Decline of Kidney Function in ZSF1 Rats.

Chronic kidney disease (CKD) progression is associated with persisting oxidative stress, which impairs the NO-sGC-cGMP signaling cascade through the formation of oxidized and heme-free apo-sGC that cannot be activated by NO. Runcaciguat (BAY 1101042) is a novel, potent, and selective sGC activator that binds and activates oxidized and heme-free sGC and thereby restores NO-sGC-cGMP signaling under oxidative stress. Therefore, runcaciguat might represent a very effective treatment option for CKD/DKD. The potential kidney-protective effects of runcaciguat were investigated in ZSF1 rats as a model of CKD/DKD, characterized by hypertension, hyperglycemia, obesity, and insulin resistance. ZSF1 rats were treated daily orally for up to 12 weeks with runcaciguat (1, 3, 10 mg/kg/bid) or placebo. The study endpoints were proteinuria, kidney histopathology, plasma, urinary biomarkers of kidney damage, and gene expression profiling to gain information about relevant pathways affected by runcaciguat. Furthermore, oxidative stress was compared in the ZSF1 rat kidney with kidney samples from DKD patients. Within the duration of the 12-week treatment study, kidney function was significantly decreased in obese ZSF1 rats, indicated by a 20-fold increase in proteinuria, compared to lean ZSF1 rats. Runcaciguat dose-dependently and significantly attenuated the development of proteinuria in ZSF1 rats with reduced uPCR at the end of the study by -19%, -54%, and -70% at 1, 3, and 10 mg/kg/bid, respectively, compared to placebo treatment. Additionally, average blood glucose levels measured as HbA1C, triglycerides, and cholesterol were increased by five times, twenty times, and four times, respectively, in obese ZSF1 compared to lean rats. In obese ZSF1 rats, runcaciguat reduced HbA1c levels by -8%, -34%, and -76%, triglycerides by -42%, -55%, and -71%, and cholesterol by -16%, -17%, and -34%, at 1, 3, and 10 mg/kg/bid, respectively, compared to placebo. Concomitantly, runcaciguat also reduced kidney weights, morphological kidney damage, and urinary and plasma biomarkers of kidney damage. Beneficial effects were accompanied by changes in gene expression that indicate reduced fibrosis and inflammation and suggest improved endothelial stabilization. In summary, the sGC activator runcaciguat significantly prevented a decline in kidney function in a DKD rat model that mimics common comorbidities and conditions of oxidative stress of CKD patients. Thus, runcaciguat represents a promising treatment option for CKD patients, which is in line with recent phase 2 clinical study data, where runcaciguat showed promising efficacy in CKD patients (NCT04507061).

Glucometabolic control of once-weekly dulaglutide switched from DPP4 inhibitor versus daily empagliflozin add-on in patients with type 2 diabetes inadequately controlled with metformin, sulfonylurea, and DPP4 inhibitor: A randomised trial

AimsTo compare the effectiveness and safety of empagliflozin and dulaglutide in patients with type 2 diabetes (T2D) inadequately controlled by oral triple therapy. MethodsIn this 24-week, multi-center, randomized trial, patients with T2D and HbA1c level ≥7.5% (58 mmol/mol) on metformin, sulfonylurea, and dipeptidyl peptidase 4 inhibitor (DPP4-i) were randomly assigned into two groups: daily empagliflozin add-on or once-weekly dulaglutide switched from DPP4-i. The primary endpoint was changes from baseline HbA1c at 24 weeks. ResultsIn total, 152 patients were recruited to the empagliflozin-added quadruple group (n = 76) or the switched-to-dulaglutide triple group (n = 76). At week 24, both groups showed significant reduction in HbA1c level from baseline with greater reduction with empagliflozin (the mean treatment difference: –0.27% [95% CI –0.50 to –0.04, p = 0.024]) (–2.88 mmol/mol [95% CI –5.37 to –0.39], p = 0.024). Empagliflozin significantly reduced body weight from baseline to week 24 (–1.72 kg [95% CI –1.98 to –0.59, p < 0.001]). No serious adverse events were reported with either empagliflozin or dulaglutide. ConclusionsEmpagliflozin, compared with once-weekly dulaglutide switched from DPP4-i, demonstrated greater HbA1c reduction and weight loss in patients with T2D inadequately controlled with metformin, sulfonylurea, and DPP4-i.Trial registration:cris.nih.go.kr (KCT0006157)

Role of SGLT2 Inhibitors in Diabetes Management: Focus on HbA1c Levels, Weight Loss and Genetic Variation

Sodium Glucose Co-transporters-2 (SGLT2) inhibitors are the recent addition to treatment strategies for Type 2 Diabetes Mellitus (T2DM). It is a non-insulin dependent anti-diabetic therapeutic approach that eliminates plasma glucose by urination. The study was carried out with the aim of evaluating the effect of SGLT2 inhibitors on HbA1c levels and weight loss in responders and non-responders. In addition, the role of two significant variants, SLC5A2 (rs9934336) and UGT1A9 (rs72551330), affecting the inter-individual variation in response to SGLT2 inhibitors was evaluated in the study population. 200 confirmed T2DM patients on SGLT2 inhibitors were enrolled for the study. Patients with decreased HbA1c levels and body weight were categorized as responders, whereas the ones who did not show a significant decrease in these two parameters after treatment were categorised as non-responders. Association of HbA1c levels and weight loss before as well as after treatment with responders and non-responders was evaluated. Patients were screened for two significant variants, SLC5A2 (rs9934336) and UGT1A9 (rs72551330), affecting the inter-individual variation in response to SGLT2 inhibitors by Sanger Sequencing. A significant difference in HbA1c levels and weight was found in responders and non-responders before and after the treatment. However, both of the variants, SLC5A2 (rs9934336) and UGT1A9 (rs72551330), were not found to be significantly associated with the drug response. In conclusion, SGLT2 inhibitors reduced HbA1c levels and weight effectively in responders. However, the targeted gene variants need not to be involved in genetic testing before prescribing this class of drugs to T2DM patients from Malwa region of Punjab. Highlights: Treatment of Type 2 diabetes mellitus (T2DM) with Sodium Glucose co-transporter-2 (SGLT2) inhibitors is an insulin-independent method of reducing blood glucose levels by lowering renal tubular glucose reabsorption. Significant decrease in HbA1c levels and weight loss in responders was observed after the treatment with SGLT2 inhibitors. Pharmacogenetic analysis was carried out for two gene variants, SLC5A2 (rs9934336) and UGT1A9 (rs72551330), reported to be involved in inter-individual response to SGLT2 inhibitors. None of the tested variants were found to be significantly associated with inter-individual response to SGLT2 inhibitors. Pharmacogenetic testing for the two most commonly reported variants is not required for the T2DM patients on SGLT2 inhibitors from the Malwa region of Punjab.

Impact of Endoscopic Sleeve Gastroplasty in Non-alcoholic Fatty Liver Disease: a Systematic Review and Meta-analysis.

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease worldwide. Endoscopic sleeve gastroplasty (ESG) has proven to be feasible, safe, and effective in the management of obesity. We performed the first systematic review and meta-analysis evaluating NAFLD and other metabolic parameters 12months post-ESG. Four observational studies with a total of 175 patients were included. The results showed a significant (p < 0.05) reduction of 4.85 in hepatic steatosis index (95% CI - 6.02, - 3.67), 0.5 in NAFLD fibrosis score (95% CI - 0.80, - 0.19), 6.32 U/l in ALT (95% CI - 9.52, - 3.11), 17.28% in TWL (95% CI - 18.24, - 16.31), 6.31kg/m2 in BMI (95% CI - 8.11, - 4.52), 47.97% in EWL (95% CI - 49.10, - 46.84), and 0.51% in HbA1c (95% CI - 0.90, - 0.12). ESG improves liver parameters, provides weight loss, and reduces HbA1c levels in patients suffering from NAFLD.

The effect of personalized intelligent digital systems for self-care training on type II diabetes: a systematic review and meta-analysis of clinical trials.

Type 2 diabetes (T2D) is rising worldwide. Self-care prevents diabetic complications. Lack of knowledge is one reason patients fail at self-care. Intelligent digital health (IDH) solutions have a promising role in training self-care behaviors based on patients' needs. This study reviews the effects of RCTs offering individualized self-care training systems for T2D patients. PubMed, Web of Science, Scopus, Cochrane Library, and Science Direct databases were searched. The included RCTs provided data-driven, individualized self-care training advice for T2D patients. Due to the repeated studies measurements, an all-time-points meta-analysis was conducted to analyze the trends over time. The revised Cochrane risk-of-bias tool (RoB 2.0) was used for quality assessment. In total, 22 trials met the inclusion criteria, and 19 studies with 3071 participants were included in the meta-analysis. IDH interventions led to a significant reduction of HbA1c level in the intervention group at short-term (in the third month: SMD = - 0.224 with 95% CI - 0.319 to - 0.129, p value < 0.0; in the sixth month: SMD = - 0.548 with 95% CI - 0.860 to - 0.237, p value < 0.05). The difference in HbA1c reduction between groups varied based on patients' age and technological forms of IDH services delivery. The descriptive results confirmed the impact of M-Health technologies in improving HbA1c levels. IDH systems had significant and small effects on HbA1c reduction in T2D patients. IDH interventions' impact needs long-term RCTs. This review will help diabetic clinicians, self-care training system developers, and researchers interested in using IDH solutions to empower T2D patients.

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.