AjaDuo Update Podcast- Diabetes News & Clinical Updates

ImagicaHealth

Want to stay updated with the latest in diabetes research, reviews, and perspectives? Our content is curated, written, and edited by practicing healthcare professionals with clinical and scientific expertise in diabetes care. Our editorial team is comprised of highly-trained physicians. Our summaries are designed to deliver concise, relevant insights to support effective diabetes management in clinical practice. New summaries are available monthly.

  1. Sep 30

    Effects of Empagliflozin on Cardiovascular Outcomes Are Consistent Across Sociodemographic Subgroups: A Real-World Analysis From the EMPRISE Study

    OBJECTIVE We aimed to explore the heterogeneity of empagliflozin treatment effects on major adverse cardiovascular events (MACE), hospitalization for heart failure (HHF), and all-cause mortality (ACM) across sociodemographic and cardiovascular disease (CVD) subgroups of adults with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS Using 2014–2020 Medicare claims data, we examined rates of MACE (e.g., composite myocardial infarction, stroke, all-cause mortality [ACM]), HHF, and ACM among propensity score–matched individuals aged ≥65 years with T2D initiating empagliflozin compared with those prescribed dipeptidyl peptidase-4 inhibitors (DPP4is) and those prescribed GLP-1 receptor agonists (GLP-1RAs). We calculated hazard ratios(HRs) and incidence rate differences (IRDs) overall and by age, sex, race or ethnicity, socioeconomic factors, and baseline CVD. RESULTS Empagliflozin was associated with decreased risk of MACE (HR 0.77, 99.9% CI [0.69, 0.85]; IRD = −10.3 [−14.1, −6.4]); HHF (HR 0.72 [0.67, 0.79]; IRD = −18.3 [−22.9, −13.6]); and ACM (HR0.66 [0.57, 0.76]; IRD = −8.6 [−11.4, −5.8]) compared with DPP4is. Effect heterogeneity by baseline CVD was present across all outcomes on the IRD scale but only for HHF on the HR scale. Empagliflozin was also associated with decreased risk of HHF (HR 0.88 [0.81, 0.95]; IRD = −6.9 [−10.8, −3.1]) versus GLP-1RAs, with effect heterogeneity by baseline CVD on the IRD scale. No effect heterogeneity was observed by sociodemographic factors, although a numeric trend suggested greater absolute benefit in patients aged ≥75 years compared with those aged 65–74 years. CONCLUSIONS Empagliflozin reduced cardiovascular events across sociodemographic and CVD subgroups compared withboth DPP4is and GLP-1RAs, with higher absolute benefits observed in those with prevalent CVD.

  2. Sep 30

    Empagliflozin improves serum uric acid and early cardiometabolic outcomes in asymptomatic hyperuricemia among patients with type 2 diabetes- A 6-month observational study

    Abstract Asymptomatic hyperuricemia is common among patients with type 2 diabetes and has been associated with increased cardiovascular risk. However, evidence regarding the effects of empagliflozin on serum uric acid (SUA) and cardiovascular outcomes in this population remains limited. This study aimed to evaluate the impact of empagliflozin on serum uric acid (SUA) levels and early cardiometabolic outcomes in patients with type 2 diabetes and asymptomatic hyperuricemia. This 6-month observational study was conducted at a tertiary hospital in Vietnam. A total of 247 patients with type 2 diabetes were included in the cross-sectional analysis. Among them, 63 patients with asymptomatic hyperuricemia who did not meet indications for urate-lowering therapy were followed prospectively for 6 months and received either empagliflozin (10–25 mg/d) or background therapy without empagliflozin. Changes in serum uric acid SUA, HbA1c, fasting plasma glucose, and major adverse cardiovascular events (MACE) were assessed. Among the 247 participants, 73 (29.6%) had asymptomatic hyperuricemia and showed a significantly higher incidence of MACE than those without hyperuricemia (34.2% vs 8.6%; adjusted odds ratio 5.77, 95% CI: 2.49–13.39). Serum uric acid (SUA) demonstrated good predictive performance for MACE (AUC 0.741), cardiovascular mortality (AUC 0.804), and myocardial infarction (AUC 0.745). After 6 months, serum uric acid (SUA) decreased more significantly in the empagliflozin group than in the control group (−101.66 ± 76.44 vs −45.90 ± 86.36 µmol/L; P = .009). Fasting plasma glucose also improved significantly, whereas the reduction in HbA1c was not statistically significant. In patients with type 2 diabetes and asymptomatic hyperuricemia, elevated serum uric acid (SUA) was associated with increased cardiovascular risk. Empagliflozin significantly reduced serum uric acid (SUA) and improved fasting plasma glucose, with a potential trend toward favorable cardiovascular outcomes.

  3. Sep 30

    SGLT2 inhibitors for heart failure outcomes across baseline glycemic status: a systematic review and stratified meta-analysis of independent parent trial populations

    Abstract Background Sodium-glucose cotransporter 2 (SGLT2) inhibitors improve heart failure outcomes, but whether relative effects are consistent across normoglycemia, prediabetes, and diabetes/type 2 diabetes remains uncertain. Linked publications from the same randomized populations may also be double counted in publication-based syntheses.   Methods We conducted a PROSPERO-registered systematic review and stratified meta-analysis. PubMed,Embase, Web of Science Core Collection, Cochrane CENTRAL, ClinicalTrials.gov, and supplementary sources were searched from inception to June 1, 2026. Independent parent trial populations were the quantitative analysis units. Trial-reported hazard ratios were pooled with random-effects REML models, and source-defined glycemic strata were analyzed separately. Source-reported interaction tests were interpreted without estimating a new cross-trial interaction. Modified Knapp–Hartung sensitivity analysis assessed the five Wald-type models with only three or four contributing trials.   Results Seventeen eligible reports were mapped to four independent chronic heart failure trials—DAPA-HF, EMPEROR-Reduced, EMPEROR-Preserved, and DELIVER—with 20,725 randomized participants. Dapagliflozin or empagliflozin reduced the trial-defined primary composite outcome (HR, 0.78; 95% CI, 0.73 to 0.83); the small-k sensitivity remained conclusive (95% CI, 0.70 to 0.86). Pooled estimates were HR, 0.72 (95% CI, 0.57 to 0.90) for normoglycemia or normal HbA1c, HR, 0.81 (95% CI, 0.70 to 0.95) for prediabetes, and HR, 0.77 (95% CI, 0.71 to 0.84) for diabetes/type 2 diabetes. Source-reported interaction tests showed no clear effect modification but did not establish equivalence. Strict hospitalization for heart failure was reduced (HR, 0.72; 95% CI, 0.66 to 0.78). Small-k sensitivities for cardiovascular death, all-cause death, and volume depletion were less conclusive; the renal outcome remained exploratory.   Conclusions Across four parent trials of dapagliflozin or empagliflozin, the primary composite and strict hospitalization for heart failure improved, with directionally consistent relative effects across source-defined glycemic strata. These subgroup findings do not prove equivalent efficacy or exclude treatment-effect modification. Small-k sensitivity supported the primary finding while increasing uncertainty for selected secondary and safety outcomes.

  4. Sep 30

    Type 2 diabetes mellitus: emerging mechanistic insights, evolving therapeutic strategies, and future perspectives

    Abstract Type 2 diabetes mellitus (T2DM) is a complex and progressive metabolic disorder driven by interactions among genetic susceptibility, environmental influences, and metabolic dysfunction. Although insulin resistance and pancreatic β-cell dysfunction remain central to disease pathogenesis, emerging evidence highlights the contributions of chronic low-grade inflammation, gut microbiota dysbiosis, mitochondrial dysfunction, and adipose tissue remodeling in disease progression. Recent advances have shifted the management paradigm beyond glycemic control towards comprehensive cardiometabolic risk reduction, with newer therapies such as glucagon-like peptide-1 receptor agonists (GLP-1RAs), sodium-glucose co transporter-2 (SGLT2) inhibitors, and dual incretin receptor agonists demonstrating significant cardiovascular, renal, and metabolic benefits. Emerging concepts including prediabetes remission, early metabolic reversal, and precision medicine are further reshaping preventive and therapeutic strategies. However, important challenges remain regarding early risk identification, quitable access to advanced therapies, long-term treatment adherence, and implementation of evidence-based interventions in routine clinical practice. This review synthesizes contemporary mechanistic insights, evolving therapeutic approaches, and future directions in T2DM management, highlighting opportunities for personalized care and improved long term outcomes.

  5. Aug 31

    Association between different sodium–glucose co-transporter 2 inhibitors and the risk of dementia: a network meta-analysis

    Abstract Background:  Sodium-glucose cotransporter 2 inhibitors (SGLT2i),as key therapeutic agents for type 2 diabetes, have in recent years been recognized as potentially exerting europrotective effects on the central nervous system. However, systematic comparative evidence remains lacking regarding whether different Sodium-glucose cotransporter 2 inhibitors (SGLT2i) exhibit differential effects on dementia risk. By conducting a network meta-analysis to compare the association between different Sodium-glucose cotransporter 2 inhibitors (SGLT2i)and the risk of dementia onset, the relative efficacy of each drug in reducing dementia risk is determined. Methods:  A systematic search was conducted across databases including PubMed, Embase, Web of Science, and the ochraneLibrary, from their inception to the search cutoff date of 1 December 2025. Randomized controlled trials and observational studies comparing Sodium-glucosecotransporter 2 inhibitors (SGLT2i) with other antidiabetic medications or placebo, and reporting dementia outcomes, were included. A network meta-analysis employing arandom-effects model was conducted. Pooled effect sizes were expressed as hazard ratios with 95% confidence intervals. Relative efficacy among different drugs was ranked using the probability of ranking, whilst heterogeneity andconsistency were assessed. Results:  Six cohort studies involving 845,433 patients were included in this analysis. The results of the network meta-analysis indicated that canagliflozin (HR = 0.75, 95% CrI: 0.59, 0.98),Dapagliflozin (HR = 0.75, 95% CrI: 0.59, 0.98), and Empagliflozin (HR = 0.69, 95% CrI: 0.55, 0.85) significantly reduced the risk of dementia onset. Empagliflozin had the highest probability of being ranked as the most effective treatment (81.2%). However, no statistically significant differences were observed between empagliflozin and dapagliflozin or canagliflozin in the network comparisons. For Alzheimer’s disease, Dapagliflozin (HR = 0.68,95% CrI: 0.48, 0.96) and Empagliflozin (HR = 0.62, 95% CrI: 0.45, 0.87) also demonstrated significant risk reduction, whilst direct comparisons between Empagliflozin and other agents showed no significant differences. For vasculardementia, Empagliflozin (HR = 0.63, 95% CrI: 0.46, 0.87) and Canagliflozin (HR = 0.71, 95% CrI: 0.48, 0.98) also demonstrated favorable outcomes. Conclusions:  The findings of this study indicate that dapagliflozin, empagliflozin, and canagliflozin, particularly empagliflozin, demonstrate significant potential in reducing the incidence ofdementia and related cognitive impairments. Compared with Dipeptidyl peptidase-4 (DPP-4) inhibitors, these agents effectively lower the risk of dementia, Alzheimer’sdisease, and vascular dementia, offering an effective therapeutic option for diabetic patients, particularly the elderly.

  6. Aug 31

    Effects of Linagliptin on Liver Enzymes in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis

    Abstract Type 2 diabetes mellitus (T2DM) is often linked to metabolic dysfunction-associated steatotic liver disease (MASLD), a metabolic liver condition defined by excessive lipid deposition within hepatocytes and is frequently accompanied by increased circulating liver enzyme levels. Dipeptidyl peptidase-4 (DPP-4) inhibitors, such as linagliptin, may exert pleiotropic effects on hepatic metabolism; however, their effects on liver enzyme profiles remain uncertain. This systematic review and meta-analysis aimed to evaluate the impact of linagliptin on liver enzymes, including aspartate aminotransferase (AST), alanine aminotransferase (ALT),alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT), in patients with Type 2 diabetes mellitus (T2DM). A systematic literature search was performed across five electronic databases up to 11 May 2026 following the PRISMA 2020 guidelines. Randomized controlled trials and cohort studies were included, and pooled mean differences (MDs) were calculated using random-effects models. Eight studies involving 1262 participants were analyzed. Linagliptin was associated with a modest reduction in aspartate aminotransferase AST (MD −1.58 U/L, 95% CI −2.85 to −0.31) with low heterogeneity, whereas the change in alanineaminotransferase (ALT) was not statistically significant (MD −1.86 U/L, 95% CI −4.14 to 0.42), and substantial heterogeneity was observed. No significant effects were observed for gamma-glutamyl transferase (GGT), while evidence for alkaline phosphatase (ALP) was limited to a single study and was insufficient to determine the effect of linagliptin. Overall, linagliptin demonstrated limited and inconsistent effects on liver enzyme profiles.

  7. Aug 31

    Safety & efficacy of sodium glucose co-transport 2 (SGLT2) inhibitors in elderly patients with heart failure

    Abstract Introduction:  Sodium-glucose cotransporter-2 (SGLT2) inhibitors haveemerged as an important therapy in heart failure (HF). However, their safety and efficacy in elderly patients remain underexplored, as this group is often underrepresentedin clinical trials. Aim:  This study aimed to evaluate safety outcomes and describe changes in clinical parameters following initiation of Sodium-glucose cotransporter 2 (SGLT2) inhibitors in elderly Malaysian patients with heart failure. Methods:  A multicentre, single-arm, retrospective cohort study was conducted from January to December 2023 at two Malaysian hospitals. Patients aged ≥65 years initiated on empagliflozin or dapagliflozin were included. Safety outcomes assessed were acute kidney injury (AKI), orthostatic hypotension, genitourinary infections, hypoglycemia, volume depletion, and diabetic ketoacidosis (DKA). Efficacy outcomes included changes in left ventricular ejection fraction (LVEF), glycatedhaemoglobin (HbA1c), estimated glomerular filtration rate (eGFR), and New York Heart Association (NYHA) class. Descriptive statistics and chi-square tests were applied. Results:  Among 126 patients (median age 70 years), acute kidney injury (AKI) was the most frequent adverse event (12.1%), followed by orthostatic hypotension (3.0%) and urinary tract infection (1.5%). More than half (51.4%) showed left ventricular ejection fraction (LVEF) improvement, while 38.2% of diabetic patients achieved better HbA1c control. Renal functionimproved or was preserved in 40.7%, and 21.4% demonstrated New York Heart Association (NYHA) class improvement. Significant associations were observed between chronickidney disease (CKD) and acute kidney injury (AKI) (p = 0.003), and between systolic blood pressure (BP) ≤140 mmHg and both eGFR improvement (p = 0.034) and New York Heart Association (NYHA) class improvement (p = 0.029). Conclusion:  In this retrospective cohort, Sodium-glucose cotransporter 2 (SGLT2) inhibitor use was associated with observed improvements in selected cardiometabolic and functional parameters, with acute kidney injury being the most frequently recorded adverse event. However, given the single-arm retrospective design and the absence of a comparator group, these observed changes cannot be definitively attributed to Sodium-glucose cotransporter 2 (SGLT2) inhibitor therapy alone and should therefore be interpreted as associations rather than evidence of a causal treatment effect. Careful clinical monitoring remains essential, particularly in patients with underlying renal impairment.

  8. Aug 31

    Impact of empagliflozin on serum calcium and phosphate in heart failure

    Abstract Background Alterations in serum calcium (Ca2+) and phosphate (Pi)balance have been associated with poor outcomes in heart failure (HF). However, these data are mostly derived from small observational studies. Moreover, the impact of Sodium-glucose cotransporter 2 (SGLT2) inhibitors on calcium (Ca2+)and phosphate (Pi) levels have not been explored in large, randomized HF trials. Aims Using EMPEROR-Pooled data we aim to study the prognostic associations of serum calcium (Ca2+) and phosphate (Pi)in patients with heart failure (HF) and study the impact of empagliflozin on calcium (Ca2+) and phosphate (Pi) levels. Methods EMPEROR-Pooled (N=9718) was used to create serum calcium (Ca2+) and phosphate (Pi) categories (quintiles, Q). Cox andmixed-effects models were used. Results Mean calcium (Ca2+) levels were 2.35 ± 0.12 mmol/L and phosphate (Pi) 1.14±0.18 mmol/L. Compared to patients with higher calcium (Ca2+) levels (Q5, mean 2.5±0.1 mmol/L), those with lower calcium (Ca2+) (Q1, mean 2.2±0.1 mmol/L) presented more peripheral edema and higher NT-proBNP levels (P0.1), while the mortality reduction appeared more marked among patients with higher serum calcium (Ca2+)(interaction-P=0.08). Serum phosphate levels were not associated with outcomes and did not influence the effect of empagliflozin (interaction-P>0.1). Empagliflozin induced a minor increase in serum calcium (Ca2+) and phosphate(Pi) levels over time: +0.004 (0.001-0.006) mmol/L (P=0.002),and +0.030 (0.026-0.034) mmol/L (P0.001), respectively. Conclusion Low serum calcium (Ca2+) may be associated with poor outcomes but did not influence the effect of empagliflozinin a statistically significant manner.

See All (29)

About

Want to stay updated with the latest in diabetes research, reviews, and perspectives? Our content is curated, written, and edited by practicing healthcare professionals with clinical and scientific expertise in diabetes care. Our editorial team is comprised of highly-trained physicians. Our summaries are designed to deliver concise, relevant insights to support effective diabetes management in clinical practice. New summaries are available monthly.

Information