AjaDuo Update Podcast- Diabetes News & Clinical Updates

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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. Jul 31

    Cardiorenal Outcomes of Dapagliflozin vs. Empagliflozin in Advanced Chronic Kidney Disease and Diabetes

    Abstract Although sodium–glucose co-transporter-2 (SGLT2) inhibitorsprovide cardiorenal benefits, direct comparisons between dapagliflozin and empagliflozin—the two most commonly used and studied agents in this class—remain limited, particularly in patients with advanced chronic kidney disease (CKD). In the current study, we aimed to compare the cardiorenal effectiveness and safety of dapagliflozin versus empagliflozin in adults with type 2 diabetes (T2D) and stage 3B to 5 chronic kidney disease (CKD). We used the TriNetX network and identified adults with type 2 diabetes and stage 3B to 5 chronic kidney disease (CKD) newly initiating dapagliflozin or empagliflozin. Following a target trial emulation framework, we applied one-to-one (1:1) propensity score matching and Cox proportional hazards models to estimate hazard ratios (HRs) for major adverse kidney events (MAKE), major adverse cardiovascular events (MACE), all-cause mortality, and adverse events. After matching, 4,361 participants were included per group. The mean age was 67.6–67.9 years and men comprised 45.3–45.9% with a median follow-up duration of 780–790 days. Dapagliflozin users showed comparable hazard ratios (HRs) for major adverse kidney events (MAKE) (1.04; 95% CI: 0.94–1.16), major adverse cardiovascular events (MACE) (1.02; 95% CI: 0.95–1.09), all-cause mortality (0.86; 95% CI: 0.74–1.00),and adverse events (1.03; 95% CI: 0.92–1.14). However, the risk of end-stage kidney disease (ESKD) was higher with dapagliflozin (1.28; 95% CI: 1.11–1.48). We concluded that in adults with type 2 diabetes (T2D) and advanced chronic kidney disease (CKD), dapagliflozin and empagliflozin demonstrated comparable cardiorenal effectiveness and safety. Dapagliflozin was associated with a modestly higher end-stage kidney disease (ESKD) risk, but this finding warrants cautious interpretation and further study given the observational design and potential residual confounding.

  2. Jul 31

    Implementing SGLT2 Inhibitor Therapy in Line with the New NICE Guidelines for Type 2 Diabetes Management

    Abstract The latest Type 2 Diabetes Mellitus (T2DM) management guidelines from the UK National Institute for Health and CareExcellence (NICE; NG28) have raised the profile of sodium-glucose cotransporter-2 inhibitors (SGLT2is) so that they are now the preferred first-line therapy in combination with modified-release metformin (or as monotherapy where metformin is contraindicated or not tolerated) for most individuals. Previous National Institute for Health and Care Excellence (NICE) recommendations limited use to those with high Cardiovascular Disease (CVD) risk or existing Cardiovascular Disease (CVD) and/or kidney disease for first-line treatment or people with a need for additional glycaemic optimisation at later stages in the pathway. This change brings the guidelines in line with other national and international recommendations regarding sodium-glucose cotransporter-2 inhibitors (SGLT2i) use for the achievement and maintenance of glycaemic targets and lowering of progressive risk for cardiovascular, renal and metabolic (CVRM) complications. Yet, despite a plethora of evidence supporting the role that sodium-glucose cotransporter-2 inhibitors (SGLT2is) can play in sustaining long-term health outcomes in people with Type 2 Diabetes Mellitus (T2DM), prescribing data from real-world clinical practice show that these therapies are under- prescribed, particularly among those populations most likely to benefit from their use (including individuals with Cardiovascular Disease or high cardiovascular, renal and metabolic risk). This latest narrative review from the Improving Diabetes Steering Committee examines the place of sodium-glucose cotransporter-2 inhibitors (SGLT2is) within the latest NG28 guidelines and likely reasons for suboptimal sodium-glucosecotransporter-2 inhibitors (SGLT2i) use, providing pragmatic advice on appropriate approaches to initiation and management in daily practice and setting perceived risks intocontext against the potential benefits. Practical tools for healthcare professionals and people with Type 2 Diabetes mellitus are included, and the Committee's previously published sodium-glucose cotransporter-2 inhibitors (SGLT2i) Prescribing Decision Tool for Type 2 Diabetes Mellitus Management has been updated and aligned with the most recent guidelines with the aim of providing a helpful and high-quality quick reference resource.

  3. Jul 31

    Meta-analysis of sodium glucose transport 2 inhibitors versus other glucose-lowering agents on the progression of diabetic retinopathy and diabetic macular edema

    Abstract Objective:  While glycemic control reduces the progression of diabetic retinopathy (DR), the effects of specific glucose-lowering drugs (GLD) remain incompletely defined. Emerging evidence suggests that sodium-glucose cotransporter‑2 inhibitors (SGLT2i) may confer protective effects on diabetic retinopathy (DR) and diabetic macular edema (DME). Research design and methods:  We reviewed human studies comparing sodium-glucosecotransporter‑2 inhibitors (SGLT2i) versus other glucose-lowering drugs (GLD) with primary outcomes of diabetic retinopathy (DR) or diabetic macular edema (DME). Random effects meta-analyses and meta-regression were performed to estimate relative risks (rr) and risk differences (rd) for retinopathy progression. Results: Of 273 identified studies, 16 met inclusion criteria, comprising 1,785,409 patients. Comparator subclasses included dipeptidyl peptidase-4 inhibitors (DPP-4i), Glucagon Like Peptide 1 -receptor agonists (GLP-1RA), sulfonylureas, and "other" glucose-lowering drugs (GLD). Sodium-glucosecotransporter‑2 inhibitors (SGLT2i) therapy was associated with significantly lower relative risks (rr) of diabetic retinopathy (DR) progression versus all glucose-lowering drugs (GLD) (rr = 0.77;95%CI:0.72,0.82,p 0.001), and eachof the subclasses. Similar reductions were observed for diabetic macular edema (DME) progression (rr = 0.75;95%CI:0.69,0.82,p 0.001). Benefits were proportional to baseline rates; for cohorts with a 20% diabetic retinopathy (DR) rate, the absolute risk difference (rd) was approximately 4%. The comparative benefit of Sodium-glucose cotransporter‑2 inhibitors (SGLT2i) was most pronounced versus sulfonylureas than to Glucagon Like Peptide 1 -receptor agonists GLP-1RA and dipeptidyl peptidase-4 inhibitors (DPP-4i). Conclusions: In patients with established diabetic retinopathy (DR) or diabetic macular edema (DME), Sodium-glucose cotransporter‑2 inhibitors (SGLT2i) may be preferred over dipeptidyl peptidase-4 inhibitors (DPP-4i) and sulfonylureas, whereas choice of Sodium-glucose cotransporter‑2 inhibitors (SGLT2i) versus Glucagon Like Peptide 1 -receptor agonists (GLP-1RA) should be guided by other comorbidities.

  4. Jul 31

    On target? Cardiovascular risk factor patterns in type 1 and type 2 diabetes: Real-world attainment of cardiovascular risk factor targets and use of medication

    Abstract Aims Adequate cardiovascular risk control prevents complications. A multifactorial approach for simultaneously managing risk factors is recommended by guidelines. We evaluated cardiovascular risk factors among Dutch diabetes outpatients and described glucose-lowering and cardiovascular prescriptions. Methods From the Dutch Pediatric and Adult Registry of Diabetes (DPARD), a cohort of 81,096 patients with type 1 diabetes (T1D) or type 2 diabetes (T2D) was derived from 2017 to 2024.Descriptive statistics reported patient characteristics and the primary outcomes cardiovascular risk targets and medication prescription patterns. Results Overall, 3,832 children had type 1 diabetes (T1D),145 children had type 2 diabetes (T2D), 35,934 adults had type 1 diabetes (T1D) and 41,185 adults had type 2 diabetes (T2D). For most cardiovascular risk factors, guideline-recommended targets were met by at least two-thirds of patients, whereas some risk factors had lower attainmentin specific subgroups. HbA1c was the least frequently reached target. The most common medications for type 1 diabetes (T1D) were fast-acting and long-acting insulins. For T2D, these were biguanides, insulins, sulfonylureas, Glucagon Like Peptide 1- agonists (GLP-1 agonists), and Sodium-glucose cotransporter‑2 inhibitors (SGLT2 inhibitors). ConclusionsThis study shows the extent to which guideline-recommended cardiovascular risk factor targets are met in children and adults with type 1 diabetes (T1D) and type 2 diabetes (T2D), which varies by age group and diabetes type. These findings may refine individually tailored strategies for management of risk factors, particularly HbA1c.

  5. Jul 2

    Integrated Cardiovascular Risk Assessment in Young Adults with Type 2 Diabetes: The “YOUNG DIABETES” Program

    Abstarct: Introduction and Objective: Early-onset type 2 diabetes (T2D) is associated with a more adverse cardiometabolic profile and increased cardiovascular (CV) risk. We aimed to characterize cardiovascular risk and subclinical atherosclerosis in young adults with type 2 diabetes (T2D) participating in the YOUNG DIABETES program. Methods: Observational study including individuals with type 2 diabetes (T2D) diagnosed at ≤50 years and current age ≤55 years enrolled in the YOUNG DIABETES clinical program. Participants underwent clinical and biochemical assessment, cardiovascular (CV) risk estimation (SCORE2-Diabetes), and carotid ultrasound to detect subclinical atherosclerosis.  Results: A total of 179 participants were included; 37% were women. Median age was 45 years [37-50] and diabetes duration 4 years [1-10]. Active smoking was present in 18% and 25% were former smokers. Median Body Mass Index (BMI) was 30.1 kg/m² [26.5-34.3], Median Glycated Hemoglobin (HbA1c) 7.2% [6.4-8.6], Median Low-Density Lipoprotein Cholesterol (LDL-C) 101 mg/dL [86-125.3], and calculated cardiovascular (CV) risk by SCORE2-Diabetes 5.2% [3.9-7].Carotid ultrasound was performed in 115 participants and identified subclinical atherosclerosis in 31% (20% had 1-2 plaques and 11% ≥3 plaques). Individuals with atherosclerosis were older (49 vs 42.5 years-old, p=0.0001), had longer diabetes duration (8 vs 2.5 years, p=0.0007), and higher HbA1c levels (7.9 vs 7%, p=0.03), No differences were observed by sex, smoking status, Body Mass Index (BMI), lipid profile, or calculated cardiovascular (CV) risk. In multivariate analysis, diabetes duration (OR 1.09 [1.01-1.17] and smoking exposure (OR 1.04 [1.00-1.07]) were independently associated with greater plaque burden.  Conclusion: In young adults with type 2 diabetes (T2D), in which SCORE2-Diabetes may underestimate cardiovascular risk, the YOUNG DIABETES program enables comprehensivecardiovascular risk stratification including detection of subclinical atherosclerosis. Carotid plaques were independently associated with longer diabetes duration and smoking exposure, highlighting the importance of early and strict glycemic control and smoking avoidance to reduce cardiovascular risk in young-onset type 2 diabetes (T2D).

  6. Jul 2

    Adoption of GLP-1RA and SGLT2i Drug Classes among Patients with Cardiovascular or Renal Indications: Evolution of Prescribing Patterns over Time

    Abstarct: Introduction and Objective: Glucagon-like peptide-1 receptor agonists (GLP-1RA) and Sodium-glucose transporter 2 inhibitors (SGLT2i) are crucial components of type 2 diabetes care, especially for adults with Cardio-vascular disease (CVD) or Diabetic kidney disease (DKD). However, early adoption of Glucagon-like peptide-1 receptor agonists GLP-1RA and SGLT2i remains low. Our aim was to evaluate the association between prescription of of Glucagon-like peptide-1 receptor agonists and Sodium–Glucose Cotransporter 2 Inhibitors medications and presence of indications for the drugs among patients with type 2 diabetes and how prescribing patters have evolved between 2016 and 2023.  Methods: We analyzed Electronic Health Record (EHR) data from adults with type 2 diabetes with one or more indications for Glucagon-like peptide-1 receptor agonists or Sodium–Glucose Cotransporter 2 Inhibitors - 1) Cardio-vasculardisease (CVD) or Diabetic kidney disease (DKD), 2) obesity, or 3) high Glycated Hemoglobin (HbA1c) level above 8% within a large regional health system. We used cluster-robust linear probability modeling with a primary outcome of receiving a Glucagon-like peptide-1 receptor agonists or Sodium–Glucose Cotransporter 2 Inhibitors prescription and predictor of indication for Glucagon-like peptide-1 receptor agonists or Sodium–Glucose Cotransporter 2 Inhibitors therapy. To examine changes over time, we introduced an interaction term of time period, 2016-2018, 2019-2021, and 2022-2023. Results: We analyzed data from 7,917 adults and 12,667 patient-time-periods. Cardiovascular disease or Diabetic kidney disease increased probability of prescription of either drug by 6.4%, obesity by 12.6%, and high A1c by 16.3% (p0.001 for all). Cardiovascular disease or Diabetic kidney disease was not associated with acceleration in prescribing rate over time, while obesity significantly accelerated prescribing in the third time period by 7% (p=0.01 for interaction). For the 2022-2023 period, estimated prescription rates were similar for obesity (50.9%) and high A1c (50.7%) but lower for Cardio-vascular disease or Diabetic kidney disease (46.7%). Conclusion: Adults with type 2 diabetes and Cardiovasculardisease or Diabetic kidney disease had increased prescribing of Glucagon-like peptide-1 receptor agonists and Sodium–Glucose Cotransporter 2 Inhibitors, continue to receive the Glucagon-like peptide-1 receptor agonists and Sodium–Glucose Cotransporter 2 Inhibitors at lower rates than adults with obesity or high A1c. Targeted clinical interventions, such as clinical decision support tools, are needed to ensure that guideline-based prescribing increases to maximize population benefit in high-risk patients with type 2 diabetes.

  7. Jul 2

    Effect of Different Treatment Durations of Sodium–Glucose Cotransporter 2 Inhibitor on Cardiovascular Outcomes in Patients with Type 2 Diabetes: A Target Trial Emulation Study Free

    Abstarct: Introduction and Objective: Despite cardiovascular benefits of Sodium-glucose cotransporter 2 inhibitors (SGLT2i), treatment persistence is suboptimal in routine clinical practice. We investigated whether longer treatment durations offer greater cardiovascular benefits. Methods: We used nationwide healthcare data of South Korea (2012-2023) to emulate a target trial comparing following treatment strategies: treated with Sodium–Glucose Cotransporter 2 Inhibitors (SGLT2i) for 1 year, 1-2 years, 2-3 years, and ≥3 years among patients with type 2 diabetes. Primary outcomes were Major adverse cardiovascular events (MACE) and hospitalization for heart failure (HHF). Cloning, censoring, and weighting methods were applied, and 5-year absolute risks, risk differences, and risk ratios were estimated using weighted Kaplan-Meier methods. Results: 1,174,088 eligible patients initiating Sodium–Glucose Cotransporter 2 Inhibitors (SGLT2i) were identified (mean age 57.3 years; 40.5% female). Compared to patients treated with Sodium–Glucose Cotransporter 2 Inhibitors (SGLT2i) for 1 year, those treated for 1-2 years, 2-3 years,and ≥3 years had progressively lower risks of Major adverse cardiovascular events (MACE) (RRs: 0.93 [95% CI, 0.90-0.96],0.82 [0.78-0.85], and 0.69 [0.67-0.72], respectively) and Hospitalization for heart failure (HHF) (RRs: 0.93 [0.90-0.97], 0.91 [0.80-0.99], and 0.74 [0.67-0.79], respectively) over a 5-year follow-up. Conclusion: Longer Sodium–Glucose Cotransporter 2 Inhibitors (SGLT2i) use was associated with progressively lower cardiovascular risk, highlighting cardioprotective benefits of sustained treatment.

  8. Jul 2

    Effects of Empagliflozin on Hepatic Glucose Production, Gluconeogenesis, and Lipolysis in Type 2 Diabetes

    Abstarct: Introduction and Objective: We previously showed that Sodium–Glucose Cotransporter 2 Inhibitors  (SGLT2 inhibitors) stimulate endogenous glucose production, offsetting their glucosuria-induced glucose lowering action, and that this effect is not explained by changes in plasma glucose, insulin, or glucagon concentration using a pancreatic clamp. To investigate the impact of Empagliflozin, a Sodium–Glucose Cotransporter 2 Inhibitor on fasting Hepatic glucose production (HGP), gluconeogenic flux, and lipolytic activity in type 2 diabetes individuals. Methods: 15individuals with type 2 diabetes (Age 57 ± 2 yrs, HbA1c = 9.0 ± 1.0%; BMI 31 ± 1.5 kg/m²) underwent a tracer-based metabolic study with 6, 6-²H2-Glucose, a stable isotope tracer used to measure hepatic glucose production (HGP) and ²H5-Glycerol, a stable isotope tracer used to measure lipolysis, or fat breakdown. Tracers were infused continuously from -180 min to 300 min (total 480 min). Heavy Water (D₂O), used to measure gluconeogenesis, the production of new glucose by the liver, was ingested on the night prior to study. Empagliflozin 25 mg was ingested at time 0 min. This design allowed quantitation of baseline (following overnight fast)and hepatic and adipocyte responses to Sodium–Glucose Cotransporter 2 (SGLT2) inhibition over a 5-hour treatment period. Results: Baseline (following overnight fast) Hepatic glucose production (HGP) and gluconeogenesis were 2.33 and 1.57 mg/kg/min, respectively. Following Empagliflozin gluconeogenesis (GNG) increased to 1.77 mg/kg/min (p0.01),while Hepatic glucose production (HGP) remained unchanged (2.43 mg/kg/min). Baseline glycerol Rate of Appearance (Ra) was 3.57 µmol/kg/min and following empagliflozin increased to 4.02 µmol/kg/min (p0.01), in association with increases inplasma glycerol (134 to 157 µmol/L, p0.01) and Free Fatty Acids (FFA) (0.51 to 0.71 µmol/L, p0.01) concentrations.  Conclusion: Sodium–Glucose Cotransporter 2 (SGLT2) Inhibition with empagliflozin: (i) stimulates gluconeogenesis, preventing the normal fasting - induced decline in Hepatic glucose production (HGP) and (ii) augments lipolysis, providing glycerol as a substrate to drive gluconeogenesis. This explains why Sodium–Glucose Cotransporter 2 inhibitors (SGLT2i) do not cause hypoglycemia.

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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.

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