Sodium-glucose co-transporter 2 inhibitors (SGLT2i) improve cardiovascular and renal outcomes in type 2 diabetes mellitus (T2DM), chronic kidney disease (CKD) and chronic heart failure (CHF). Despite clinical guideline recommendations, SGLT2i uptake in UK primary care remains suboptimal and information on utilisation is limited. This study aims to quantify and describe the UK primary care population with T2DM, CKD and/or CHF who are eligible for but not currently prescribed an SGLT2i.
A cross-sectional study was conducted using routinely collected electronic health records from the Optimum Patient Care Research Database. Adults aged ≥ 18 years on 1 July 2024 were included. Descriptive analyses estimated disease prevalence (defined by morbidity-coded diagnosis), SGLT2i eligibility (defined using NICE clinical guidelines) and current SGLT2i treatment (defined as any SGLT2i prescription in the previous 2 months) by conditions and selected characteristics. Main results are based on diagnosed disease; in a separate CKD sensitivity analysis, indicative CKD (without a morbidity code) was defined using kidney function test results.
In the study population of 9.8 million adults, prevalence was 6.52% for T2DM, 4.95% for diagnosed CKD (6.07% including indicative CKD) and 1.40% for CHF. Among all SGLT2i-eligible individuals, 17.5% were currently prescribed an SGLT2i. Current SGLT2i treatment was lowest in CKD-only patients (3.8% treated among eligible) and highest in those meeting eligibility criteria for all three indications (32.9% treated). SGLT2i treatment was lower in women and older adults.
SGLT2i therapy is significantly underutilised in UK primary care, particularly for CKD. Equitable implementation of SGLT2i clinical guidelines is vital to improve cardio-renal-metabolic care.
]]>Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as potential adjuncts to insulin therapy for type 1 diabetes mellitus (T1DM). However, interpretation of the available evidence is complicated by substantial primary-study overlap, methodological heterogeneity and variable certainty of evidence. Thus, we conducted an overlap-informed umbrella review to evaluate the efficacy and safety of GLP-1RAs as adjunctive therapy in T1DM.
We searched PubMed/MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and OpenAlex from inception to 22 June 2026, and manually screened reference lists to identify systematic reviews with meta-analyses that included randomized controlled trials (RCTs), either alone or alongside nonrandomized studies, evaluating adjunctive GLP-1RA therapy in T1DM. Methodological quality was assessed using AMSTAR 2, and primary-study overlap was quantified using a citation matrix and corrected covered area (CCA). Outcome-specific representative meta-analyses were selected, and their primary-study data were independently reanalyzed using random-effects models. Continuous and dichotomous outcomes were summarized as mean differences (MDs) and risk ratios (RRs), respectively, with 95% confidence intervals (CIs). The certainty of evidence was assessed using GRADE.
Eighteen systematic reviews with meta-analyses encompassing 56 unique primary studies (35 RCTs and 21 nonrandomized studies) were included. The calculated CCA was 19.6%, indicating a very high degree of primary-study overlap, largely driven by the ADJUNCT ONE and ADJUNCT TWO trials. Adjunctive GLP-1RA therapy reduced HbA1c (MD, −0.23% [95% CI, −0.30 to −0.17]; moderate certainty), body weight (MD, −3.93 kg [−4.29 to −3.56]; moderate certainty) and total daily insulin dose (MD, −5.74 IU/day [−7.30 to −4.17]; low certainty). No significant improvement was observed in time in range (MD, 1.99% [95% CI, −1.17 to 5.15]; very low certainty). No statistically significant increases were observed in severe hypoglycemia (RR, 0.83 [95% CI, 0.36–1.91]; low certainty) or diabetic ketoacidosis (RR, 0.67 [95% CI, 0.16–2.86]; low certainty). However, GLP-1RAs increased the risks of nausea (RR, 2.88 [95% CI, 2.20–3.76]; high certainty), vomiting (RR, 3.11 [1.94–4.97]; high certainty), and withdrawal due to adverse events (RR, 2.10 [1.42–3.12]; high certainty), whereas the risk of diarrhoea was not significantly increased (RR, 1.88 [0.82–4.33]; low certainty).
Adjunctive GLP-1RA therapy was associated with a modest reduction in HbA1c and clinically relevant reductions in body weight and insulin requirements, without a significant improvement in time in range. Gastrointestinal adverse events were increased, whereas the risks of diabetic ketoacidosis and severe hypoglycemia remained uncertain. These findings do not support routine use but suggest a potential role in selected individuals for whom weight reduction and lower insulin requirements are therapeutic priorities.
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]]>The long-term cardiometabolic effects of alcohol reduction remain unclear. We evaluated the long-term associations of sustained alcohol reduction with glycemic, blood pressure, and lipid profiles.
We conducted a pooled sequential target trial emulation using annual health examination data from Japanese employees (2008–2023). Eligible participants were aged ≥ 40 years and consumed ≥ 20 g/day of ethanol at baseline. Participants subsequently reducing alcohol intake to < 20 g/day formed the intervention group; those maintaining ≥ 20 g/day formed the control group. We applied inverse probability weighting to estimate the per-protocol effect of sustained alcohol reduction. We used weighted generalized estimating equations to estimate longitudinal trajectories of fasting plasma glucose (FPG), systolic blood pressure (SBP), diastolic blood pressure (DBP), triglycerides, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol.
Among 266 699 eligible trial entries, 30 280 and 229 946 trial entries were included in the intervention and control groups, respectively. Alcohol reduction was associated with persistently lower FPG, SBP, DBP, and triglycerides over 15 years. At Year 15, between-group differences were −1.8 mg/dL for FPG, −3.4 mmHg for SBP, −2.2 mmHg for DBP and −20.4 mg/dL for triglycerides (all p ≤ 0.005). Conversely, HDL cholesterol levels were consistently lower and LDL cholesterol levels modestly higher in the intervention group. Blood pressure-lowering effects were consistent across genders, and findings were broadly consistent across sensitivity, subgroup, and dose-transition analyses.
Sustained alcohol reduction improved long-term FPG, blood pressure, and triglycerides. These findings support alcohol reduction as a potentially beneficial lifestyle intervention for improving cardiometabolic profiles.
]]>To evaluate dose-normalised time in range (dn-TIR) and its log relative change (Δdn-TIR) as measures of within-person glycaemic change relative to total daily insulin exposure following hybrid closed-loop therapy (HCL/AID).
We conducted a retrospective two-cohort study of people with type 1 diabetes commencing hybrid closed-loop/automated insulin delivery (HCL/AID) therapy in Australia and the United Kingdom (UK). dn-TIR was calculated as time in range (TIR) 3.9–10.0 mmol/L (70–180 mg/dL) divided by total daily insulin dose (TDD) and Δdn-TIR as log[(TIR/TDD)post/(TIR/TDD)pre].
The study comprised 86 people living with type 1 diabetes in Australia and 288 in the UK. In the fixed Australian dn-TIR cohort, TIR increased from 53.2% ± 20.7% to 70.4% ± 14.6% (n = 86; p < 0.001), whereas mean TDD changed from 53.3 to 52.0 units/day (n = 86; p = 0.724). Median Δdn-TIR was 0.224 [IQR: −0.033, 0.583]. In the UK cohort, TIR increased from a median 54% [34, 68] to 66% [54, 74] (n = 257; p < 0.001), whereas mean TDD changed from 44.1 to 46.3 units/day (n = 242; p = 0.152). Median Δdn-TIR was 0.194 [IQR: −0.097, 0.541].
HCL/AID therapy improved TIR relative to TDD in two real-world cohorts. dn-TIR and Δdn-TIR are not replacements for established CGM metrics or direct measures of insulin sensitivity; they may provide an adjunct longitudinal description of whether glycaemic improvement was accompanied by proportionately greater, similar or lower insulin exposure.
]]>Low-density lipoprotein cholesterol (LDL-C) goal attainment is central to primary atherosclerotic cardiovascular disease (ASCVD) prevention, but LDL-C may not fully reflect the burden of apolipoprotein B (ApoB)-containing atherogenic particles. The prevalence and clinical correlates of residual ApoB elevation among adults who have attained PREVENT risk–stratified LDL-C goals remain unclear.
This cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) 2005–2016 from adults aged 30–79 years without known ASCVD. The primary analytic sample included participants with 10-year PREVENT-ASCVD risk ≥ 3% who attained risk-stratified LDL-C goals. Residual ApoB elevation was defined as ApoB ≥ 90 mg/dL for PREVENT-ASCVD risk 3% to < 10% and ≥ 70 mg/dL for risk ≥ 10%. Survey-weighted analyses were used to estimate prevalence and identify factors associated with residual ApoB elevation.
Among 3857 adults with PREVENT-ASCVD risk ≥ 3%, 908 (23.5%) attained risk-stratified LDL-C goals. Of these, 128 had residual ApoB elevation, corresponding to a weighted prevalence of 17.7% (95% CI, 14.5%–21.4%). The prevalence was substantially higher among participants with triglycerides 150–400 mg/dL than among those with triglycerides < 150 mg/dL (43.6% vs. 4.3%; p < 0.001). In multivariable logistic regression, triglycerides of 150–400 mg/dL were strongly associated with residual ApoB elevation (adjusted OR, 15.87; 95% CI, 8.28–30.41; p < 0.001). Higher odds were also observed for PREVENT-ASCVD risk ≥ 10%, obesity, metabolic syndrome and advanced cardiovascular-kidney-metabolic stages (CKM Stages 2–4). The association with triglycerides was consistent across exploratory subgroups and robust in sensitivity analyses.
Among U.S. adults without known ASCVD who attained PREVENT risk–stratified LDL-C goals, residual ApoB elevation was common and strongly associated with triglyceride elevation. The prognostic and clinical significance of this discordant phenotype remains to be established.
]]>To evaluate whether intravitreal ranibizumab (IVR) frequency is associated with longitudinal renal markers in diabetic macular oedema (DMO) and whether the expected systemic renal and haematological effects of SGLT2 inhibition are reproduced.
In this post hoc sub-analysis of the prospective COMET randomised controlled trial, 53 participants were analysed. The estimated glomerular filtration rate (eGFR), haematocrit (Hct), and urinary albumin-to-creatinine ratio (UACR) were assessed over 48 weeks using linear mixed-effects models with the treatment group, week, group-by-week interaction, and cumulative IVR as fixed effects.
Baseline eGFR was preserved (72.2 ± 18.5 mL/min/1.73 m2) despite common albuminuria (median UACR 50.6 mg/gCr); mean cumulative IVR at week 48 was 7.00 ± 4.42. Cumulative IVR was not significantly associated with eGFR (−0.22 mL/min/1.73 m2 per injection; 95% CI −0.59 to 0.15; p = 0.25), ln(UACR), or Hct. The SGLT2 inhibitor reproduced an early eGFR dip and Hct rise.
No statistically significant exposure-response association was detected between cumulative IVR and renal markers within the COMET trial cohort and dosing range. Because all participants received IVR and the sample size was modest, small cumulative renal effects cannot be excluded.
Trial Registration: University Hospital Medical Information Network Center (UMIN000057674); Japan Registry of Clinical Trials (jRCTs031180210, parent COMET trial)
]]>Antenatal corticosteroids (ACS) promote foetal lung maturation in pregnancies at risk of preterm birth; however, in gestational diabetes mellitus (GDM), they can exacerbate maternal glycemia and contribute to adverse neonatal outcomes. Clinical guidelines offer limited direction on optimal treatment adjustment.
To synthesize the evidence on glycaemic responses and management strategies following ACS exposure in individuals with GDM.
A systematic review of Embase, MEDLINE and CENTRAL in October 2025 in accordance with PRISMA guidelines. Studies reporting on glycaemic outcomes and/or management strategies following ACS exposure in individuals with GDM were included.
Twenty studies were included. Maternal glycemia rose predictably after ACS, with hyperglycaemia typically emerging within 9–16 h, peaking over the subsequent 24–72 h and often persisting up to 5 days. Among individuals managed with medical nutrition therapy or oral hypoglycaemic agents at baseline, insulin initiation ranged from 13% to 91%. Among those already using insulin, 67%–88% required dose escalation, with mean increases typically ranging from 47% to 91%. Pregnancy-adapted intravenous insulin (IVI) pathways reported higher time-in-range and fewer hyperglycaemic/hypoglycaemic events than adult IVI protocols. However, emerging evidence suggests that structured, pregnancy-specific subcutaneous insulin protocols may achieve comparable or improved glycaemic control.
ACS exposure in GDM is associated with a predictable but variable, transient deterioration in maternal glycaemia. GDM-specific evidence suggests that structured pregnancy-adapted monitoring and insulin-adjustment pathways may help attenuate post-ACS hyperglycaemia. However, the evidence remains heterogeneous and largely observational. Prospective studies are needed to validate GDM-specific algorithms, clarify thresholds for insulin initiation or escalation and define indications for subcutaneous versus IVI.
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]]>PROSPERO registration number
CRD420251105442.
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