AjaDuo Update Podcast- Diabetes News & Clinical Updates

Objective: This study aimed to compare the effects of empagliflozin-metformin versus empagliflozin- linagliptin combination therapy on cardiovascular parameters and anemia in patients with type 2 diabetes mellitus (T2DM).Study Design and setting: An analytical study was conducted over 12 weeks at National Medical Centre Hospital, Karachi. Methodology: T2DM patients were randomly assigned to either the Empagliflozin 12. 5 mg with Metformin 500mg or Empagliflozin 10mg with Linagliptin 5mg. Clinical assessments were conducted at baseline Week 0, 4, and 12, focusing on C-reactive protein levels, blood pressure, temperature, heart rate, respiratory rate, ECG findings, hemoglobin levels, BMI, and glycated hemoglobin (HbA1c) and cardiac examination was performed in all visits. Descriptive statistics were used to compare outcomes between the groups.Results: The comparative analysis of empagliflozin–metformin (EM) and empagliflozin–linagliptin (EL) regimens demonstrated notable differences in outcomes. HbA1c decreased significantly in both groups, but the EL group showed a greater reduction by week 12 (p = 0.021, OR = 1.65, 95% CI: 1.05 2.58). BMI declined in both arms, but intergroup difference was not statistically significant (p = 0.078). CRP levels dropped more in the EL group, reaching statistical significance (p = 0.037, OR = 1.43, 95% CI: 1.01–2.11). Cardiovascular parameters, including systolic BP (p = 0.116) and diastolic BP (p = 0.098), remained stable, showing no significant differences. ECG (QTc interval) changes were also nonsignificant (p = 0.316). Hemoglobin levels showed no significant difference between groups at week 12 (p = 0.212). Overall, both regimens were effective and cardiovascularly safe, though EL provided superior benefits in glycemic control (HbA1c, p = 0.021) and anti-inflammatory effect (CRP,p = 0.037).Conclusion: The combination of empagliflozin with either metformin or linagliptin proved to be effective treatment with cardiovascular safety.

Background: Diabetics with coronavirus disease 2019 (COVID-19) manifest more adverse clinical outcomes with elevated rates of death. It has been suggested that the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pathway of entrance into the host cell might be assisted bydipeptidyl peptidase-4 (DPP4), leading to inflammation and cytokine storm, with replication into the airways and unfavorable effects in the lungs. Consequently, the goal of this systematic review is to investigate the most recent data on the effect of DPP-4i (dipeptidyl peptidase-4 inhibitor)medications on clinical outcomes, mainly mortality among COVID-19 patients. Methods: By conducting a systematic search using PubMed and the Cochrane library, observational studies were identified to examine the association between DPP-4i medications and clinical outcomes including mortality, intensive care unit and hospital admissions. The methodologies of included studies were assessed utilizing the Newcastle–Ottawa Scale (NOS). Results: A total of nineteen studies were included with sample sizes varying from over 100 patients to 2.8 million and variant follow-up durations from 30 days up to discharge or death. Most of thepopulation across the studies had COVID-19 for the first time, and the majority were hospitalized.Similarly, mortality definition varied among studies with different time points consisting of 30-day mortality, in-hospital mortality, or all-cause mortality. The majority of the studies identified no effect on mortality by DPP-4i, while a considerable proportion revealed beneficial effects; only four studies showed increased mortality.Conclusions: Real-world data from this review suggested a safe use of DPP-4i among COVID-19 patients; however, randomized clinical trials are required to confirm the beneficial outcomes and safe use.

Introdution: Type 2 Diabetes Mellitus (T2DM) and Chronic Kidney Disease (CKD) are highly interconnected, impacting global health. Sodium-Glucose Cotransporter-2 Inhibitors (SGLT2i)and Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs) offer promising benefits for glycemiccontrol, cardiovascular health, and kidney protection. This review compares their effectiveness in enhancing kidney function and glycemic control for T2DM patients with CKD.Methods: A narrative review was conducted using the PICO framework, searching the PubMed database and online search (ScienceDirect and Google Scholar) for English-language observational research articles published between 2020 and 2025. Articles focused on SGLT2i and GLP-1RA therapies in T2DM patients with CKD, assessing kidney function and glycemic control. Fifteen articles were selected from an initial 706. The keyword use is “comparing” AND “effectiveness” AND “SGLT-2 inhibitor” AND “GLP-1 RA” AND “kidney function” AND “glycemic control” AND “T2DM” AND “CKD” AND “patients”.Results: SGLT2 inhibitors consistently demonstrated strong renal protective effects, including slower eGFR decline and reduced kidney failure progression. GLP-1RAs excelled in glycemic control, weight management, and cardiovascular event reduction. While SGLT2i generally appeared superior for direct renal protection, some studies suggested comparable renal outcomes. Real-world data largely supported these findings, enhancing clinical applicability.Conclusion: SGLT2 inhibitors are recommended for T2DM patients with CKD, especially those at higher renal risk. GLP-1RAs are valuable for glycemic control, weight, and cardiovascular benefits. Their complementary mechanisms suggest potential for additive benefits in combination therapy, necessitating further research to optimize patient outcomes.

Background: Diabetes is a major public health concern in India, contributing significantly to morbidity and mortality. With variations in disease burden across states, a detailed understanding of trends in incidence, prevalence, and Disability Adjusted Life Years (DALYs) is essential for targeted interventions.Methods: This study utilized Global Burden of Disease (GBD) data from 1990 to 2021 to examine trends in diabetes across Indian states. Age-standardized incidence, prevalence, mortality, and DALYs were analyzed using Join point regression to estimate Annual Percentage Change (APC). Autoregressive Integrated Moving Average (ARIMA) models were employed to project diabetes trends up to 2031. While the GBD data provide robust national and regional estimates, their modeled nature may not capture the full spectrum of local epidemiological variations.Results: Diabetes incidence increased from 162.74 to 264.53 per 100,000 between 1990 and 2021, with an APC of 0.63%. Joinpoint analysis identified episodic surges in incidence, with APCs of 2.25% during 1996–1999 and 2.07% during 2005–2011, suggesting intervals of accelerated increase relative to the gradual progression typically observed in chronic conditions. Mortality rose from 23.09 to 31.12 per 100,000 (APC: 0.12%). Southern and Western states, such as Tamil Nadu and Goa, exhibited the highest prevalence and DALYs. Forecasted trends indicate that by 2031, the prevalence will reach 8585.45 per 100,000, and DALYs will exceed 1241.57 per 100,000.Conclusion: The burden of diabetes in India has risen markedly over the past three decades. These findings underscore the urgent need for health policies that emphasize lifestyle modifications and improved healthcare access. A comprehensive approach that integrates primary prevention through community-based health education, dietary counseling, and initiatives to promote physical activity with secondary prevention measures such as systematic screening and timely clinical management, is essential for effective diabetes control and management in high-burden states.

AbstractBackground: Mounting evidence indicates that Type 2 diabetes mellitus (T2DM) is a public healthchallenge globally, and its occurrence is anticipated to surge in the forthcoming years. Dipeptidyl peptidase‐4 (DPP‐4) serves as a target for its treatment, with its inhibitors effectively preserving the levels of glucose‐dependentinsulinotropic peptide and glucagon‐like peptide 1(GLP‐1). This review presents an overview of the therapeutic possibilities of six frequently employed DPP‐4 inhibitors (DPP‐4is) (Sitagliptin, saxagliptin, vildagliptin, linagliptin, alogliptin and teneligliptin) in managing T2DM, focussing on their characteristics, mechanism of action, advantages and side effects in comparison with alternative oral antidiabetic drugs as well as the possibility of using in silico method in advancing its timely and cost‐effective production.Methods: A literature search was conductedusing the major search engines such as PubMed/Medline, Scopus, and Google Scholar, etc. employing terms like ‘Type 2 diabetes mellitus (T2DM), DPP‐4 inhibitors, and Dipeptidyl peptidase‐4’, etc. to identify relevant studies.Results: Our findings indicate that DPP‐4is stimulate secretion of insulin and suppress secretion of glucagon by elevating endogenous GLP‐1 concentrations without an intrinsic hypoglycaemia risk. Although these agents share a common mechanism of action, their considerable structuralheterogeneity may lead to distinct pharmacological characteristics. Literature shows that DPP‐4is have a promising safety profile in comparison with other oral antidiabetic medications, however, certain safety aspects require additional exploration. Different DPP‐4is havedemonstrated comparable safety and tolerability, whether used alone or in combination with other antidiabetic medications. Besides, it has been shown that in silico method could be employed in development of DPP‐4is. Further research is necessary to ascertain whether differences amongDPP‐4 inhibitors might influence the occurrence of specific adverse effects.Conclusion: DPP‐4 inhibitors remain effective and well tolerated options for managing T2DM.

AbstractAims: Guidelines for type 2 diabetes recommend add-on agents when metformin alone fails to provide adequate glycaemic control. However, early combination therapy may benefit health outcomes. We conducted a systematic review and meta-analysis to investigate this question.Methods: We searched MEDLINE and Cochrane CENTRAL (up to July 2012) without language restrictions. We sought randomized controlled trials (RCTs) evaluating initial combination therapy with metformin versus metforminmonotherapy in patients with untreated type 2 diabetes. Weighted mean differences (WMDs) for changes from baseline and relative risks (RRs) [with 95% confidence intervals (CIs)] were calculated using random-effects model.Results: In 15 RCTs (N = 6693), the mean age range was 48.4–62.7 years; mean baseline glycosylated haemoglobin (A1c) was 7.2–9.9% and mean diabetes duration was 1.6–4.1 years, with median follow-up of 6 months and with 13 comparisons for A1c change, 14 comparisons for A1c goal attainment of <7% and 13 comparisons for change in fasting plasma glucose (FPG). Drugs combined with metformin included thiazolidinediones (TZDs), insulin secretagogues, dipeptidylpeptidase-4 (DPP-4) inhibitors or sodium glucose transporterase (SGLT-2) inhibitors. Compared to metformin alone, combination therapy with metformin provided statistically significant reductions in A1c (WMD −0.43%, 95% CI −0.56, −0.30), increases in attainment of A1c goal of less than 7% (RR 1.40, 95% CI 1.33–1.48) and reductions in FPG (WMD −14.30 mg/dl, 95% CI −16.09, −12.51).Conclusions: These results suggest a potential benefit of initial combination therapy on glycaemic outcomes in diabetes compared to metformin monotherapy across awide range of baseline A1c levels. Further research should explore if early combination treatment may also affect longer term health outcomes in diabetes.

AbstractImportance: Sodium-glucose cotransporter 2 (SGLT2) inhibitors favorably affect cardiovascular (CV) and kidney outcomes; however, the consistency of outcomes across the class remains uncertain.Objective: To perform meta-analyses that assess the CV and kidney outcomes of all 4 available SGLT2 inhibitors in patients with type 2 diabetes.Study Selection: One hundred forty-five records were initially identified; 137 were excluded because of study design or topic of interest. As a result, a total of 6 randomized, placebo controlled CV and kidney outcomes trials of SGLT2 inhibitors in patients with type 2 diabetes were identified, with contributory data from 9 publications. All analyses were conducted on the total patient population of these trials.Main Outcomes and Measures: Outcomes included time to the first event of (1) the composite of major adverse CV events of myocardial infarction, stroke, or CV death, and each component, (2) the composite of hospitalization for heart failure (HHF) or CV death (HHF/CV death) and each component, and (3) kidney composite outcomes. For outcomes in the overall trial populations and in selected subgroups, hazard ratios (HRs) and 95% CIs were pooled and meta analyzed across trials.Results: Data from 6 trials comprised 46 969 unique patients with type 2 diabetes, including 31 116 (66.2%) with atherosclerotic CV disease. The mean (SD) age of all trial participants was 63.7 (7.9) years; 30 939 (65.9%) were men, and 36 849 (78.5%) were White. The median number of participants per trial was 8246 (range, 4401-17 160). Overall, SGLT2 inhibitors were associated with a reduced risk of major adverse CV events (HR, 0.90; 95% CI, 0.85-0.95; Q statistic, P = .27), HHF/CV death (HR, 0.78; 95% CI, 0.73-0.84; Q statistic, P = .09), and kidney outcomes (HR, 0.62; 95% CI, 0.56-0.70; Qstatistic, P = .09), with no significant heterogeneity of associations with outcome. Associated risk reduction for HHF was consistent across the trials (HR, 0.68; 95% CI, 0.61-0.76; I2 = 0.0%), whereas significant heterogeneity of associations with outcome was observed for CV death (HR, 0.85; 95% CI,0.78-0.93; Q statistic, P = .02; I2 = 64.3%). The presence or absence of atherosclerotic CV disease did not modify theassociation with outcomes for major adverse CV events (HR, 0.89; 95% CI, 0.84-0.95 and HR, 0.94; 95% CI, 0.83-1.07, respectively; P = .63 for interaction), with similar absence of associations with outcome modification by prevalentatherosclerotic CV disease for HHF/CV death (P = .62 for interaction), HHF (P = .26 for interaction), or kidney outcomes (P = .73 for interaction).Conclusions and Relevance: In this meta-analysis, SGLT2 inhibitors were associated with a reduced risk of major adverse CV events; in addition, results suggest significant heterogeneity in associations with CV death. The largest benefit across the class was for an associated reduction in risk for HHF and kidney outcomes, with benefits for HHF risk being the most consistent observation across the trials.

Abstract Introduction and Objective: To analyze the efficacy, safety and tolerability of SGLT2i and DPP-4i combination vs placebo as add-on or initial therapy in Asian patients with T2DM as available data is heterogenous in Asian population.Methods: Database like MEDLINE, Embase, and Cochrane review was searched until August 2023 to identify trials evaluating the efficacy and safety of combination therapy (SGLT-2i+ DPP-4i and/or metformin) in subjects with Asianorigin. Primary outcome was mean difference in glycemic and extra-glycemic effects like body weight and systolic BP, and hypoglycemia risk at least for 24 weeks. A meta-analysis was conducted to measure standardized mean differences (SMD), and other relevant statistics for clinical parameters. Meta analysis with systemic review was performed using CMA v4 software.Results: A total of nine RCTs were included with 2170 patients (three studies as initial combination, three of SGLT2i as add-on to DPP-4i and three of DPP-4i as add onto SGLT2i in a sequential manner). Overall, the combination of SGLT2i and DPP-4i demonstrated a significant decrease in HbA1c relative to DPP-4i [-0.95% (95% CI: -1.09, -0.81)] or SGLT2i [-0.97% (95% CI:-1.11, -0.83)] compared to placebo. When SGLT2i combined with DPP-4i, either as initial or sequential combination, a marked lowering of HbA1c level was reported. Patients treated in combination treatment revealed the favorableeffects on the body weight and systolic BP compared to subjects on DPP-4 inhibitors, but no difference in subjects of SGLT2i arm. There were no statistically significant differences in the incidence of adverse events.Conclusion:SGLT2i and DPP-4i combination show significant glycemic improvement in Asian population. Safety indicators did not show significant differences. More high-quality studies are required to validate these findings.

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