To estimate the magnitude of reduction in major adverse cardiovascular events (MACE) that would be observed in clinical practice from adding tirzepatide to standard of care treatment.

Population based cohort study, using a design, data, and analytical approach previously benchmarked against randomised trials.

Two national US claims databases, May 2022 to May 2025.

52 971 participants aged ≥40 years with type 2 diabetes and established atherosclerotic cardiovascular disease who initiated tirzepatide (n=35 353) or sitagliptin (n=17 618), a cardiovascular outcome neutral comparator serving as a placebo proxy. Baseline characteristics were well balanced between treatment groups after propensity score overlap weighting.

The main outcome, MACE, was a composite of myocardial infarction, stroke, and all cause mortality and its individual components. Follow-up started the day after treatment initiation and continued until occurrence of the outcome, disenrollment from the health plan, treatment discontinuation or switching, or one year. Safety outcomes included infections requiring hospital admission and infection related mortality. Two negative control outcomes, lumbar radiculopathy and abdominal hernia, were analysed to assess residual confounding.

At one year, the weighted one year risk of MACE was 2.9% (95% confidence interval (CI) 2.5% to 3.4%) in the tirzepatide group and 4.4% (3.8% to 4.9%) in the sitagliptin group (risk difference -1.4%, 95% CI -2.1% to -0.7%; number needed to treat (NNT)=70), corresponding to a hazard ratio of 0.68 (95% CI 0.58 to 0.80). For individual MACE components, tirzepatide was associated with a lower hazard for myocardial infarction (hazard ratio 0.67, 0.52 to 0.87; NNT=130), whereas ischaemic stroke showed no meaningful difference (0.91, 0.64 to 1.28; NNT 2500). Infections requiring hospital admission were lower with tirzepatide (0.64, 0.55 to 0.75; NNT=48), as was infection related mortality (0.40, 0.26 to 0.61; NNT=200) and all cause mortality (0.55, 0.42 to 0.72; NNT=122). Negative control outcomes showed no association.

In this cohort study using an approach benchmarked against randomised trials, initiating tirzepatide reduced the risk of MACE compared with a placebo proxy among people with type 2 diabetes and established atherosclerotic cardiovascular disease. Reductions in infection related events suggest broader non-atherosclerotic biological mechanisms may contribute to the observed benefit. This study shows how trial-anchored evidence from clinical practice can estimate the expected cardiovascular benefit of initiating tirzepatide beyond standard background treatment and inform shared decision making.

ClinicalTrials.gov NCT07203677.

To investigate the behavioural and social determinants of type 2 diabetes mellitus (T2DM) self-care adherence in South Ethiopia using the integrated health belief model (HBM) and health-related quality-of-life (HRQoL) frameworks.

A cross-sectional study.

Three public hospitals in South Ethiopia: Wolaita Sodo University Comprehensive Hospital, Humbo Primary Hospital and Boditi Primary Hospital.

404 systematically sampled adults aged 18-60 years with a confirmed diagnosis of T2DM who had been attending follow-up clinics for at least 12 months. Exclusion criteria included newly diagnosed T2DM, pregnancy, severe comorbidities or critical illness and unwillingness to participate.

The primary outcome was adherence to diabetes self-care, assessed using the Summary of Diabetes Self-Care Activities scale across five domains: diet, physical activity, medication intake, blood glucose monitoring and foot care. Good adherence was defined as engagement in recommended behaviours on ≥50% of days per week. Secondary outcomes included socio-demographic factors, clinical variables, HBM constructs (perceived susceptibility, severity, benefits, barriers, cues to action and self-efficacy) and HRQoL domains (physical, psychological, social and environmental).

Of 404 participants, 58.4% demonstrated good adherence. In multivariable analysis, insulin-only treatment (AOR=3.0; p<0.001), having comorbidities (AOR=2.02; p=0.007) and poor glycaemic control (AOR=3.6; p=0.003) were positively associated with adherence. Factors associated with poor adherence included low income (AOR=0.18; p=0.002), living alone (AOR=0.19; p=0.012), low self-efficacy (AOR=0.18; p<0.001) and poor psychological health (AOR=0.53; p=0.024).

The findings challenge the direct application of standard behavioural models in low-resource settings. Structured factors, such as poverty, can overwhelm psychological mechanisms. Effective interventions must integrate economic support with psychological care to improve self-care adherence.

Diabetes mellitus (DM) is associated with negative psychological conditions, specifically burnout, in cases where there is less glycemic control and longer illness time. The aim of this study was to adapt and validate the Diabetes Burnout Scale [DBS, Escala do Burnout na Diabetes (EBD)] into European Portuguese, as an evaluation measure tailored to the Portuguese context.

The scale was translated, retranslated and adapted. This study resorted to online and in-person collection of a convenience sample of people with DM. Reliability tests and convergent validation tests were performed, using the EQ-5D-5L and Problem Areas in Diabetes Scale 5 (PAID-5) as reference. Factor structure was evaluated using fit and invariance tests. Associations between the total score of the scale and variables like the respondents' most recent glycated hemoglobin (HbA1c) and socioeconomic index were analyzed.

A total of 1070 people with DM participated, 50.6% male and 49.3% female, with an average age of 56.0 ± 15.7 years and an average time since diagnosis of 20 ± 12.3 years. A three-factor structure was ascertained with a good fit: exhaustion, detachment and loss of control - invariant by sex and DM type. The internal consistency, as given by Cronbach's Alpha, was 0.885. Spearman's correlation showed the relation between EBD total score and EQ-5D-5L utility index (ρ = -0.382, p < 0.001), PAID-5 total score (ρ = 0.638, p < 0.001), and most recent HbA1c (ρ = 0.295, p < 0.001).

The EBD scale was successfully adapted and validated for European Portuguese.

Patients with myasthenia gravis (MG) are frequently associated with other autoimmune diseases. However, the temporal relationship between autoimmune diseases and MG remains unclear. This study aimed to evaluate the rates and temporal patterns of autoimmune diseases during the 10 years preceding MG diagnosis.

This retrospective population-based cohort study analyzed claims data from the Korean National Health Insurance Service between 2010 and 2021 and included individuals aged ≥20 years. MG was defined using the International Classification of Diseases, 10th Revision (ICD-10) code (G70.0) and Rare Intractable Disease registration (V012). Each MG case was matched with 10 controls by age, sex, and index year. Outcomes were autoimmune thyroid disease (AITD), systemic lupus erythematosus (SLE), seropositive rheumatoid arthritis (SRA), Sjögren syndrome (SjS), psoriasis, type 1 diabetes mellitus (T1DM), Crohn disease, and ulcerative colitis occurring during the 10 years before the index year. Rate ratios (RRs) and 95% CIs were estimated using Poisson regression models for 0-2, 2-5, and 5-10 years before the index year.

A total of 8,355 patients with MG and 83,550 matched controls were included. The mean age (SD) was 53.7 (16.0) years, and 44.1% were male. Patients with MG had a higher rate of any autoimmune disease during 10 years before diagnosis than controls (RR 2.12, 95% CI 1.97-2.28), with the highest rates in 0-2 years before diagnosis (RR 4.27, 95% CI 3.78-4.83). SLE (RR 4.87, 95% CI 2.71-8.77), SjS (RR 4.75, 95% CI 3.01-7.50), AITD (RR 3.66, 95% CI 3.29-4.07), and SRA (RR 2.45, 95% CI 1.89-3.19) showed the strongest associations. Psoriasis (RR 1.68, 95% CI 1.25-2.25) and T1DM (RR 2.03, 95% CI 1.52-2.71) were associated with MG only within 0-2 years before diagnosis, whereas Crohn disease and ulcerative colitis were not associated.

Autoimmune diseases were more frequent in the years preceding MG diagnosis than in controls, particularly within 2 years before diagnosis. Strong associations were observed for SLE, SjS, AITD, and SRA. However, these findings should be interpreted with caution because of limitations of administrative claims data.

This study examined changes in body composition and bone mineral density (BMD) over 12 months in people with obesity and type 1 diabetes (T1D) treated with a GLP-1 receptor agonist alone (GLP-1RA) or a dual glucose-dependent insulinotropic polypeptide (GIP/GLP-1RA).

This real-world observational study included 70 people with obesity and T1D treated with GLP-1RA alone or dual GIP/GLP-1RA. Dual-energy X-ray absorptiometry (DEXA) was used to quantify regional and total fat mass, lean mass, bone mineral content (BMC) and BMD at baseline and after 12 months of treatment. Overall changes were quantified, and changes stratified by percentage weight loss using repeated measures analysis.

Over 12 months body weight (-6.33%; 95% CI: -7.92, -4.73; p < 0.001), HbA1c (-0.48%; 95% CI: -0.74, -0.22; p < 0.001), total tissue fat (-1.42%; 95% CI: -2.47, -0.36; p = 0.009), fat mass (-5.90%; 95% CI: -10.50, -1.57; p = 0.001), and lean mass (-1.75%; 95% CI: -3.50, -0.48; p = 0.005) decreased, while total BMC and BMD remained unchanged. Total lean mass loss was associated with body weight loss (R² = 0.36, p < 0.001).

In people with obesity and T1D, 12-month GLP-1RA alone or dual GIP/GLP-1RA therapy resulted in clinically meaningful weight loss, improved glycaemic control, preferential fat mass reduction, modest lean mass loss, and preservation of total BMD. People achieving > 10% weight loss derived the greatest metabolic benefit without compromising bone health, although the loss of lean mass was greater.

Dyslipidemia is prevalent among Nigerians with diabetes mellitus (DM), but its treatment has not been well-studied. The objective of this study was to determine the prevalence, treatment rates and control of dyslipidemia among DM patients in northern Nigeria.

We conducted a multicenter, cross-sectional study of dyslipidemia in DM patients, and noted cardiovascular disease (CVD) risk factors, lipid-lowering treatments, body mass index, blood pressure, HbA1c, lipid profile, glomerular filtration rate and proteinuria. Outcome measures were the rate and treatment of dyslipidemia and attainment of low density lipoprotein cholesterol target for primary prevention of CVD. Binomial logistic regression was used to analyze associations between participant characteristics and dyslipidemia. Hosmer-Lemeshow goodness-of-fit test was used to evaluate the model fit. Statistical analysis was performed with the SPSS version 25 program.

The study enrolled 403 participants (58.8% females), of whom 59.6% had dyslipidemia. Besides DM and dyslipidemia, other risk factors for CVD were hypertension (56.8%), obesity (52.6%), chronic kidney disease (36.5%), atrial fibrillation (7.9%), heart failure (5.0%), cigarette smoking (4.7%), excess alcohol use (2.0%), and previous CVD (14.4%). Logistic regression analysis showed dyslipidemia was significantly associated with female gender (odds ratio = 1.68, P = 0.029) and proteinuria (odds ratio = 2.26, P = 0.004). Among those with dyslipidemia, 51.3% took lipid-lowering treatments comprising statins (50.8%) and clofibrate (2.9%). None took other lipid-lowering treatments, and only 17.1% attained the target for primary prevention of CVD.

Three-fifths of patients had dyslipidemia, but only a sixth attained the treatment target. Treatment for dyslipidemia included statins and fibrates, but not niacin, ezetimibe, bempedoic acid, icosapent ethyl, inclisiran or PCSK9 inhibitors recommended for those who failed intensive statin therapy. There is the need for better access to non-statin treatment and physician adherence to clinical practice guidelines.

As the global incidence of diabetes and its associated treatment costs rise, continuous glucose monitors (CGMs) constitute a valuable tool for patient self-monitoring. However, market dominance of a few well-known brands, predominantly in populations with type 1 diabetes, limits the adoption of more cost-effective alternatives that might offer improved clinical outcomes. To address this, an expert roundtable evaluated barriers to efficient CGM use, identifying challenges such as regional care board variations, lack of patient-centred prescribing and insufficient training for both patients and healthcare professionals (HCPs). The panel suggested implementing more individualised prescribing, such as accessible readers for elderly patients, and expanding HCP education. Moreover, more streamlined integration of CGM data into electronic health records would reduce admin burden, while helping to facilitate remote monitoring to encourage patient self-management. Individualised CGM prescription, alongside improved workflows for HCPs around prescribing and addressing patient queries, could significantly lower healthcare costs while improving diabetes care in the UK.

Amylin is a pancreatic beta-cell hormone that sits at a systems hub connecting key aspects of energy metabolism. Amylin physiologically controls satiation, slows gastric emptying and limits postprandial glucagon release, while its actions also link homeostatic eating controls with reward driven behaviours via defined central nervous system pathways. Further, at least under certain conditions, aggregating amylin exerts a strong pathophysiological impact on the destruction of pancreatic beta-cells in Type 2 diabetes mellitus (T2D), providing a plausible explanation for why a T2D-like disease entity is only observed in a few mammalian species. This review will provide a brief summary of selected aspects of our current understanding of the biology of amylin and outlines how this knowledge has recently been translated into effective pharmacotherapy for obesity and diabetes, including long-acting analogs combination approaches with other peptide hormones.