This study evaluated the cost-effectiveness (from the United States [US] societal perspective) of tirzepatide at its maximum-tolerated-dose (MTD) compared to semaglutide (MTD), both administered adjunct to a reduced-calorie diet and increased physical activity. The analysis focused on individuals with obesity (body mass index [BMI] ≥ 30 kg/m²), or overweight (BMI ≥27 to <30 kg/m² + ≥1 obesity-related complication), using data from the head-to-head Phase-3 SURMOUNT-5 trial (patients without type 2 diabetes [T2D]).

This patient-level simulation modeling study assessed the cost and long-term clinical outcomes of tirzepatide (MTD) versus semaglutide (MTD), using data from the SURMOUNT-5 trial population. The modeled population were at risk of developing obesity-related complications including cardiovascular disease (CVD) and obstructive sleep apnea (OSA), amongst others. These outcomes were modeled using cardiometabolic parameters including weight, systolic blood pressure, high-density lipoprotein, glycated hemoglobin (HbA1c) and total cholesterol, by assessing their impact on healthcare and wider societal costs, quality of life, and mortality. Incremental cost-effectiveness ratios (ICERs; cost/quality-adjusted life year [QALY]) and incremental net health benefit (iNHBs) were calculated, and uncertainty was assessed through sensitivity and scenario analyses.

Tirzepatide (MTD) was estimated to be less costly and more efficacious compared to semaglutide (MTD) with per patient cost savings of $41,688, 0.506 QALYs gained and positive iNHB of 0.784, indicating a net health benefit for tirzepatide. The model predicted that per 1,000 patients, 70 fewer patients will develop T2D, 10 fewer will develop CVD with tirzepatide (MTD) and patients spend 3.07 more years living with moderate/severe OSA when treated with semaglutide (MTD).

Based on this simulation model, using head-to-head SURMOUNT-5 trial data, tirzepatide (MTD) had lower total costs and higher QALYs compared to semaglutide (MTD). This supports that tirzepatide (MTD) is a cost-effective treatment option for individuals with obesity or overweight compared to semaglutide (MTD).

Cardiac autonomic neuropathy (CAN) is a frequent but under-recognised complication of diabetes that may exacerbate cardiovascular risk after stroke. This study aimed to characterise circadian patterns of heart rate (HR) and HR variability (HRV) in patients with acute ischaemic stroke, comparing those with and without type 2 diabetes.

We conducted a retrospective case-control study of 157 patients with acute ischaemic stroke who underwent 7-day continuous electrocardiographic (ECG) monitoring (80 with type 2 diabetes, 77 without diabetes). Patients with paroxysmal atrial fibrillation, insufficient ECG data (<7 days), or obstructive sleep apnoea were excluded. HR and HRV indices (standard deviation of NN intervals [SDNNs], root mean square of successive differences [RMSSDs], pNN50, high-frequency [HF], low-frequency [LF] and LF/HF ratio) were derived from 5-min segments. Circadian variation was analysed using generalised additive mixed models (GAMMs) adjusted for demographic, clinical and treatment factors.

Compared with patients without diabetes, those with type 2 diabetes exhibited persistently higher HR and lower HRV across both time- and frequency-domain measures. Differences were most pronounced at night and in the early morning, indicating blunted autonomic fluctuations despite a preserved HR rhythm. Among patients with diabetes, poorer glycaemic control (glycated haemoglobin [HbA1c] > 7% [53 mmol/mol]) was associated with higher HR and lower HRV, particularly during nocturnal hours, supporting a dose-response relationship.

Type 2 diabetes is associated with attenuated circadian autonomic regulation after ischaemic stroke, characterised by elevated HR and reduced HRV, most evident during sleep and early morning periods. Continuous ECG monitoring may facilitate early detection of nocturnal autonomic dysfunction, and interventions that enhance parasympathetic tone-such as improved glycaemic control and potentially cholinergic modulation-warrant further investigation to mitigate post-stroke cardiovascular risk.

Co-existence of multiple cardiovascular-kidney-metabolic (CKM) conditions, such as chronic kidney disease (CKD), type 2 diabetes (T2D), and cardiovascular disease, is common. The interconnected nature of CKM conditions emphasizes the need for an interprofessional approach to patient care. As the prevalence of people with CKM conditions continues to rise in the United States and the burden on the health care system increases, clinical pharmacists are well-positioned to provide support within interprofessional teams and improve patient access to care through delivery of education, assessments and monitoring, and optimal initiation and maintenance of guideline-directed medical therapy (GDMT).

This scoping review explored interprofessional team-based interventions that incorporated pharmacists into the management of CKM conditions in the U.S. Searches were conducted in Embase and MEDLINE for relevant studies published in English between January 1, 2015 and February 14, 2025, in a patient population with > 5% of patients with both CKD and one or more cardiovascular or metabolic conditions. Outcomes investigated included estimated glomerular filtration rate, urine albumin-to-creatinine ratio, glycated hemoglobin, and systolic and diastolic blood pressure, as well as patient and physician satisfaction with pharmacist interventions.

A total of 28 studies met the eligibility criteria, including 18 randomized clinical trials, 4 pilot studies, and 6 observational studies. Effective interventions generally included longitudinal follow-up with multiple pharmacist visits over time, comprehensive pharmacist involvement including patient assessment, monitoring, and medication management, and direct deployment of pharmacist-led interventions through collaborative practice agreements.

This scoping review demonstrates an integral and direct role for pharmacists in improving outcomes for patients with CKM conditions in interprofessional settings. However, there is a need for more robust studies that investigate cardiovascular, kidney, and metabolic outcomes in these patients.

Type 2 diabetes (T2D) results from the interplay of genetic susceptibility and an unhealthy lifestyle, but their combined effects are not well studied. We examined whether unhealthy modifiable behaviors were associated with similar increases in the risk of incident T2D in individuals with different levels of genetic risk. Among 332,251 UK Biobank participants without diabetes, we constructed a multiancestry genetic risk score (GRS) based on 783 T2D-associated variants, categorized into tertiles. Lifestyle was classified as healthy, intermediate, or unhealthy based on baseline self-reported smoking status, BMI, physical activity level, and diet quality. Cox proportional hazards regression models were used to generate adjusted hazard ratios (HRs) for T2D and associated 95% CIs. During follow-up (median 13.6 years), 13,128 (4.0%) participants developed T2D. GRS (P < 0.001) and lifestyle classification (P < 0.001) were independently associated with increased risk of T2D. Compared with a healthy lifestyle, an unhealthy lifestyle was associated with increased risk in all genetic risk strata, with adjusted HRs ranging from 7.11 to 16.33. High genetic risk and an unhealthy lifestyle were the most significant contributors to T2D development. Individuals at all levels of genetic risk can substantially mitigate their T2D risk through lifestyle modifications.

Both genetic susceptibility and an unhealthy lifestyle are known to be associated with elevated type 2 diabetes (T2D) risk. However, their combined effects on T2D risk are not well studied. In this large prospective cohort study of more than 332,000 individuals, unhealthy lifestyle factors were associated with risk of incident T2D within and across different levels of genetic risk. These findings suggest individuals at all levels of genetic risk can greatly mitigate their risk of T2D by adhering to a healthy lifestyle.

Despite the high prevalence of diabetes, hypertension and dyslipidemia among Malaysian adults, there are gaps in management and control of these diseases. Evidence suggests that implementation of the Chronic Care Model in primary health care (PHC) can improve patients' clinical outcomes, quality of life and reduce the overall social burden. This study aims to describe the PHC interventions for diabetes, hypertension and/or dyslipidemia in Malaysia and to identify existing gaps by mapping against Chronic Care Model domains.

This study reports a section of a larger scoping review and focuses on studies with interventions. PubMed, Embase, Scopus and MyMedR were searched systematically from inception until 31 December 2024, using keywords pertaining to "diabetes", "hypertension", "dyslipidemia", "PHC" and "Malaysia". Study selection was independently performed by reviewers in pairs.

A total of 32 interventions were identified across 39 publications. The earliest study was published in 2012 and the highest number of publications was seen in 2020. Most studies were conducted in the states of Kelantan and Selangor. The two most common components of intervention were patient education (n = 16) and the use of decision aids (n = 11). Interventions predominantly targeted type 2 diabetes (72%) and the Chronic Care Model domains of self-management support and delivery system design, with very few addressing community linkages (n = 3). Intermediate clinical outcomes (HbA1c, blood pressure, and cholesterol) were the most common measures.

This review highlights key gaps in PHC interventions for these three chronic diseases. While self-management and delivery systems are well-addressed, current efforts remain heavily focused on individuals with diabetes, with limited attention to community components and rural populations. There is a need to broaden the intervention scope beyond diabetes and invest in stronger community linkages for a more equitable system in Malaysia.

Impaired post-prandial skeletal muscle glucose uptake plays a pivotal role in the development of type 2 diabetes mellitus (T2DM), yet pharmacological strategies to enhance muscle glucose uptake are limited. Previous (pre)clinical research revealed that β₂-adrenergic receptor (β2-AR) stimulation enhances glucose uptake, but its clinical relevance in individuals susceptible to developing T2DM is unknown. Here we determined in a double-blinded, placebo-controlled, crossover study (ClinicalTrials.gov-identifier: NCT04921306), the effects of a 4-week treatment with the β₂-adrenergic agonist clenbuterol (40 μg/day) on insulin-stimulated glucose uptake in the quadriceps muscle (primary outcome) and brown adipose tissue (BAT) (secondary outcome) using ¹⁸F-FDG PET-MRI during a hyperinsulinemic-euglycemic clamp in individuals with overweight or obesity (age: 40-70 years, BMI: 25-35 kg/m²). A total of 14 participants were recruited and randomized. Insulin-stimulated glucose uptake tended to improve in vastus lateralis (15%, p = 0.072) and increased significantly in the hamstring (13%, p = 0.039) muscle, while BAT uptake (p = 0.720) remained unaffected. These findings suggest potential therapeutic benefits of β₂-AR stimulation for improving muscle-specific glucose uptake in individuals with or at risk for developing diabetes.

Combination therapy of glucokinase activators and sodium-glucose cotransporter-2 inhibitors may exhibit potent glucose-lowering effects and improvement of β-cell function and insulin sensitivity in patients with type 2 diabetes mellitus, given their complementary mechanisms of action. However, the safety, pharmacokinetic interactions and pharmacodynamic effects of such combinations remain unexplored. To address this gap, we conduct an open-label, sequential phase I trial (ClinicalTrials.gov, NCT03790787) evaluating the dorzagliatin and the sodium-glucose cotransporter-2 inhibitor empagliflozin in patients with type 2 diabetes mellitus and obesity in the US. After strict screening against the inclusion/exclusion criteria, 16 participants are deemed eligible. Participants receive sequential treatments-empagliflozin alone, empagliflozin plus dorzagliatin, and dorzagliatin alone-five days for each regimen, followed by a comprehensive assessment of pharmacokinetic profiles and safety. The primary outcomes included GMR for C_max and AUC_0-24h of empagliflozin and dorzagliatin of pharmacokinetic parameters and the incidence of adverse events, abnormal vital signs, abnormal clinical laboratory findings, and 12-lead electrocardiogram abnormalities of safety profile. A total of 27 adverse events occurs in 9 participants (56.3%), the majority of which are mild, with the exception of one case of moderate constipation. No clinically significant findings or changes attributable to study drug treatment were found in clinical chemistry, hematology and urinary analyses, and observed in vital signs, 12-lead electrocardiogram and physical examination. The geomean ratio and their associated 90% confidence intervals for both maximum plasma concentration (empagliflozin: 98.43% (84.07%, 115.25%); dorzagliatin: 103.94% (90.45%, 119.44%)) and area under the concentration-time curve from 0 to 24 h (empagliflozin: 97.53% (94.35%, 100.82%); dorzagliatin: 99.65% (95.25%, 104.25%)) of empagliflozin and dorzagliatin fall entirely within the conventional bioequivalence range of 80.00% to 125.00%. No pharmacokinetic drug-drug interaction is observed, and the treatment exhibits a favorable safety profile with good overall tolerability.

High-density lipoprotein (HDL) functionality is emerging as a novel predictor of disease outcomes. The role of HDL functionality in patients with diabetes-related amputations is unexplored. We aimed to assess changes in HDL functionality in people with diabetes who had minor amputations and to determine the relationship between HDL functionality and wound closure (WC).

Thirty patients with diabetes mellitus (DM) and 11 without (non-DM) undergoing minor amputations were recruited. Blood was collected at baseline (DM, n = 30; non-DM, n = 11), 1 month (DM, n = 22; non-DM, n = 5), and 6 months (DM, n = 14; non-DM, n = 3) postamputation and from 20 healthy gender- and age-matched control participants. HDL was isolated from plasma and functionality markers of macrophage cholesterol efflux, and anti-inflammatory and proangiogenic capacities in endothelial cells were assessed. The study adhered to Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines.

HDL-cholesterol (HDL-c) levels positively correlated with WC (r = 0.44, p < 0.05). Cholesterol efflux capacity of DM HDL was reduced 1-month postamputation (-44% vs. non-DM HDL, d = -1.5, p < 0.05). Following inflammatory stimulation, DM HDL-treated cells had elevated levels of C-X3-C motif chemokine ligand 1 (+92%, d = 0.9), C-C motif chemokine ligand 2 (+49%, d = 0.8), vascular cell adhesion molecule 1 (+67%, d = 0.9), and intracellular adhesion molecule 1 (+58%, d = 0.9) (vs. non-DM HDL, p < 0.05). The capacity of endothelial cells to form tubules reduced linearly with time following DM HDL treatment (p < 0.05), concomitant with reduced vascular endothelial growth factor A (-47% vs. non-DM HDL, d = -1.2, p < 0.05). Endothelial cells treated with HDL from participants with delayed WC (<50%, 1-month postamputation) exhibited increased v-rel avian reticuloendotheliosis viral oncogene homolog A (RELA) expression (+52%, d = 1.2, p < 0.05). The impairment of HDL functionality in DM was concomitant with reduced apolipoprotein AI (-34%, d = 1.2) and paraoxonase 1 (-32%, d = -1.3, vs. non-DM, p < 0.05) protein in HDL 1-month postamputation.

An HDL panel, including HDL-c and HDL functionality and composition, could be used in early screening to identify patients who may benefit from early therapeutic intervention, guiding wound care management.

Impaired HDL functionality, mediated through changes in HDL composition, may contribute to delayed wound healing.

A substantial number of cats develop diabetes mellitus (DM), a serious endocrine disorder that can lead to other physiologic complications. While DM management can be complex, successful control that alleviates the patient's clinical signs and avoids hypoglycemia is achievable in most cats. Diabetic remission is also possible. The 2026 AAHA Diabetes Management Guidelines for Cats retain clinically relevant information from the 2018 AAHA Diabetes Management Guidelines and present new findings and expert opinions. Subjects such as pathophysiology, diagnosis, how to treat and monitor cats receiving SGLT2 inhibitors, various insulin options for cats, how to monitor cats receiving insulin, diet and physical activity recommendations, advantages and disadvantages of at-home glucose monitoring devices, diagnosing and treating diabetic ketoacidosis, and client education are all discussed. The guidelines also cover how to identify patients who are at risk of developing DM and how to differentiate DM from transient or mild hyperglycemia.

Evidence supporting the benefits of continuous glucose monitoring (CGM) in reducing diabetes-related complications remains scarce. This study aimed to investigate the association between CGM and diabetes-related complications, specifically diabetic ketoacidosis (DKA) and severe hypoglycemia in children and adolescents with type 1 diabetes mellitus (T1DM).

From the Korean Nationwide Cohort (2016-2022), we included children and adolescents (aged <19 years) with T1DM who received rapid-acting insulin between 2019 and 2022. The primary outcomes were DKA and severe hypoglycemia. Adjusted hazard ratios (HRs) for the primary outcomes were compared between CGM users and non-users using Cox proportional hazards regression models. Additionally, among the CGM users, the frequencies of DKA and severe hypoglycemia were compared before and after CGM initiation using a paired t-test.

This study included 3,765 children and adolescents (2,313 CGM users and 1,452 non-users). During a median follow-up of 2.7 years, CGM users showed a lower risk of DKA (adjusted HR, 0.44; 95% confidence interval [CI], 0.35 to 0.56) and severe hypoglycemia (adjusted HR, 0.48; 95% CI, 0.29 to 0.79) than non-users. Among CGM users, the mean frequency of DKA decreased by 64%, and that of severe hypoglycemia decreased by 57% after CGM initiation (P<0.001 for both).

In this nationwide cohort study, CGM was associated with a reduced risk of DKA and severe hypoglycemia in children and adolescents with T1DM.