Diabetes management often requires insulin therapy, yet adherence to daily injections can be challenging due to complexity, injection pain, and fear of hypoglycemia. Basal Insulin Fc (BIF) is a novel once-weekly insulin analog designed to simplify regimens, improve adherence, and enhance glycemic control. This meta-analysis evaluates the efficacy and safety of BIF compared to once-daily insulin degludec.

A systematic search of PubMed, Google Scholar, EBSCO, ScienceDirect, and the Cochrane Library, along with ClinicalTrials.gov, was conducted up to November 2024 to identify RCTs comparing BIF with insulin degludec. The search employed MeSH terms like "type 1 diabetes mellitus," "type 2 diabetes mellitus," "once weekly basal insulin Fc," and "insulin degludec." Studies were screened in accordance with PRISMA guidelines, and data on glycemic outcomes, safety, and patient demographics were extracted. Statistical analysis included pooled mean differences (MD) and risk ratios (RR) with 95% confidence intervals (CIs) using random-effects models. Heterogeneity was assessed using the I2 statistic, and sensitivity analyses were conducted for cases of high heterogeneity. Subgroup and meta-regression analyses assessed moderators such as diabetes type, insulin status, follow-up duration, and heterogeneity.

Five RCTs with 2,562 participants (Type 1 and Type 2 diabetes) were included. BIF showed non-inferiority to degludec in HbA1c reduction (MD 0.03, p = 0.37) and percentage time in range (MD 0.56, p = 0.27). No significant differences were observed in self-monitored fasting blood glucose (MD 2.73, p = 0.40) or clinically significant hypoglycemia (RR 1.00, p = 0.95). However, BIF increased time spent below range (MD 0.30, p = 0.0004) and was associated with higher treatment-emergent adverse events (RR 1.12, p = 0.006). The subgroup analysis highlighted differences in hypoglycemia risks between Type 1 and Type 2 diabetes.

BIF offers comparable glycemic control to insulin degludec while reducing injection frequency, potentially enhancing adherence. However, increased hypoglycemia risks in certain subgroups and higher adverse event rates warrant further evaluation.

The online version contains supplementary material available at 10.1007/s40200-025-01602-y.

Diabetes ranks among the most common chronic conditions in childhood and adolescence. It is unique among chronic conditions, in that clinical outcomes are intimately tied to how the child or adolescent living with diabetes and their parents or carers react to and implement good clinical practice guidance. It is widely recognized that the individual's perspective about the impact of trying to manage the disease together with the burden of self-management should be addressed to achieve optimal health outcomes. Standardized, rigorous assessment of behavioural and mental health outcomes is crucial to aid understanding of person-reported outcomes alongside, and in interaction with, physical health outcomes. Whilst tempting to conceptualize person-reported outcomes as a focus on perceived quality of life, the reality is that health-related quality of life is multi-dimensional and covers indicators of physical or functional health status, psychological well-being and social well- being.

In this context, this Consensus Statement has been developed by a collection of experts in diabetes to summarize the central themes and lessons derived in the assessment and use of person-reported outcome measures in relation to children and adolescents and their parents/carers, helping to provide a platform for future standardization of these measures for research studies and routine clinical use.

This consensus statement provides an exploration of person-reported outcomes and how to routinely assess and incorporate into clincial research.

Smart systems for multiple daily injections (Smart MDI) integrate continuous glucose monitoring, connected insulin pens, smartphone apps, and cloud-based data storage to provide bolus and corrective dose suggestions, reminders/alerts, automatic tracking and sharing of insulin therapy, and glycemic data to users, caregivers, and providers. This is an expert consensus on the clinical value of Smart MDI and critical points for implementation in adults and children/adolescents with diabetes.

A nominal group technique combined with the estimate-talk-estimate approach was employed to achieve consensus among panel members from the Italian Intersociety Technology and Diabetes Study Group with expertise in pediatric and adult diabetes care.

The expert consensus indicated that glycemic profiles can be improved by using bolus dose suggestions based on glucose values, planned meals, the insulin-to-carbohydrate ratio, correction factors, and consideration of insulin-on-board. Automatic remote sharing of patient data on glycemia and insulin therapy allows clinicians to make more appropriate and timely therapeutic recommendations based on objective data. Dose tracking, bolus reminders/alerts, and reduced hypoglycemia and associated anxiety achieved through Smart MDI may improve adherence.

Smart MDI can reduce treatment burden while improving the daily experiences and glycemic outcomes for adults and children/adolescents with type 1 or type 2 diabetes. However, high-quality clinical data are lacking, and more evidence is needed to compare the effects of Smart MDI and other advanced insulin delivery systems on glycemic and patient-reported outcomes.

ONWARDS 5 evaluated the effectiveness and safety of insulin icodec (icodec) titrated with a dosing guide app (icodec with app) versus once-daily insulin analogs in insulin-naive adults with type 2 diabetes. The insulin glargine U300 (glargine U300) stratum was too small to enable a robust post hoc efficacy comparison. Augmentation methodology was applied to increase the glargine U300 group size using real-world data (RWD), to facilitate efficacy comparisons of icodec with app versus glargine U300, and to demonstrate the potential of the augmentation methodology to strengthen underpowered treatment comparisons (AUGMENT study).

ONWARDS 5 data were augmented with RWD collected from the US Ambulatory Electronic Medical Records database. Randomized and augmented comparisons (propensity-score-matched) between icodec with app and glargine U300 were weighted to provide a fully augmented estimate of the primary outcome (change in glycated hemoglobin [HbA1c] after 52 weeks). Data were adjusted for trial effects. Sensitivity analyses were conducted.

The nonaugmented randomized estimated treatment difference (ETD; 95% CI) between icodec with app and glargine U300 (trial stratum) for change in HbA1c was - 0.21 (- 0.70 to 0.28) percentage points. After adjusting for trial effects, the overall fully augmented ETD (95% CI) was - 0.33 (- 0.68 to 0.01) percentage points numerically in favor of icodec with app, although not statistically significant. Sensitivity analyses supported the findings.

Using augmented data, the precision of the change in HbA1c estimate was increased compared with the trial stratum analysis alone. These findings help to validate the principle of utilizing augmentation to strengthen trial outcomes.

The ONWARDS 5 trial is registered with ClinicalTrials.gov (NCT04760626).

Diabetes mellitus is a growing global health issue, especially in low- and middle-income countries like Ethiopia. To the best of our knowledge, the impact of diabetes knowledge on glycemic control in Ethiopia has not been documented. This study assessed diabetes knowledge and its relationship with glycemic control among Type 2 diabetes (T2DM) patients in Debre Berhan, Ethiopia.

A cross-sectional study was conducted involving 380 patients diagnosed with T2DM who were receiving care at two hospitals in Debre Berhan from January 1 to March 30, 2024. Patients' knowledge was assessed using the modified Diabetes Knowledge Questionnaire (DKQ-18), categorizing outcomes as either good or poor. Glycemic control was evaluated using hemoglobin A1c (HbA1c) levels. Logistic regression analyses were conducted to identify predictors of poor diabetes knowledge. Correlation analysis was used to evaluate the relationship between knowledge and glycemic control.

Among the 380 participants, 75.2% were older than 45 years, and 51.3% were male. Overall, 62.4% of participants had poor knowledge of diabetes. Additionally, 72.6% had poor glycemic control, with HbA1C levels ≥7%. The mean average diabetes knowledge score was 7.9 (SD = 3.49) out of 18, and the median HbA1C was 8%. Diabetes knowledge was significantly associated (p < 0.05) with patients' educational level, occupation, family history of diabetes, and glycemic control. The Spearman correlation coefficient between HbA1C and diabetes knowledge scores was -0.166 (p = 0.001), suggesting a weak but statistically significant inverse relationship between knowledge scores and HbA1C levels.

The study found that the majority of patients had a low level of diabetes knowledge. Enhancing diabetes education and identifying additional factors that influence glycemic control are crucial for achieving optimal diabetes management in Ethiopia. Public health initiatives should prioritize enhancing diabetes knowledge through targeted educational programs and resources to support effective diabetes management and achieve optimal glycemic control.

Inadequate glycemic control in patients with type 2 diabetes (T2DM) is a major public health problem and a significant risk factor for the progression of diabetic complications.

To evaluate the effects of intensive and supportive glycemic management strategies over a 12-month period in individuals with T2DM with glycated hemoglobin (HbA1c) ≥ 10% and varying backgrounds of glycemic control.

This prospective observational study investigated glycemic control in patients with poorly controlled T2DM over 12 months. Participants were categorized into four groups based on prior glycemic history: Newly diagnosed, previously well controlled with recent worsening, previously off-target but now worsening, and HbA1c consistently above 10%. HbA1c levels were monitored quarterly, and patients received medical, educational, and dietary support as needed. The analysis focused on the success rates of good glycemic control and the associated factors within each group.

The study showed significant improvements in HbA1c levels in all participants. The most significant improvement was observed in individuals newly diagnosed with diabetes: 65% achieved an HbA1c target of ≤ 7%. The results varied between participants with different glycemic control histories, followed by decreasing success rates: 39% in participants with previously good glycemic control, 21% in participants whose glycemic control had deteriorated compared to before, and only 10% in participants with persistently poor control, with mean HbA1c levels of 6.3%, 7.7%, 8.2%, and 9.7%, respectively. After one year, 65.2% of the "newly diagnosed patients", 39.3% in the "previously controlled group", 21.9% in the "previously off-target but now worsened'" group and 10% in the "poorly controlled from the start" group had achieved HbA1c levels of 7 and below.

In poorly controlled diabetes, the rate at which treatment goals are achieved is associated with the glycemic background characteristics, emphasizing the need for tailored strategies. Therefore, different and comprehensive treatment approaches are needed for patients with persistent uncontrolled diabetes.

Artificial intelligence (AI) is increasingly being used to diagnose complications of diabetes. Artificial intelligence is technology that enables computers and machines to simulate human intelligence and solve complicated problems. In this article, we address current and likely future applications for AI to be applied to diabetes and its complications, including pharmacoadherence to therapy, diagnosis of hypoglycemia, diabetic eye disease, diabetic kidney diseases, diabetic neuropathy, diabetic foot ulcers, and heart failure in diabetes.Artificial intelligence is advantageous because it can handle large and complex datasets from a variety of sources. With each additional type of data incorporated into a clinical picture of a patient, the calculation becomes increasingly complex and specific. Artificial intelligence is the foundation of emerging medical technologies; it will power the future of diagnosing diabetes complications.

Diabetes affects 10.5% of adults globally, with type 2 diabetes accounting for 90-95% of cases. Achieving optimal glycemic control is crucial yet challenging, particularly with insulin therapy, where 30-50% of patients fail to meet treatment targets. Telemedicine can improve diabetes management but generates vast amounts of data, burdening healthcare professionals. Integrating clinical decision support tools into telemonitoring systems may enhance care efficiency and glycemic control.

The trial is a multicenter 3-month, three-arm, open-label, randomized controlled trial. The trial aims to enroll 51 participants with type 2 diabetes on insulin therapy. Participants will be divided with a 3:1:1 ratio into telemonitoring with decision support, telemonitoring without decision support, and usual care groups. The study employs connected insulin pens, continuous glucose monitors (CGMs), and activity trackers to enable telemonitoring. Outcomes measured include CGM time in range, HbA1c, hypo- and hyperglycemia incidents, total daily insulin dose, body weight, treatment satisfaction, and adherence.

Telemonitoring with decision support has the potential to revolutionize diabetes management by offering personalized treatment suggestions, thereby reducing the burden on healthcare professionals, and improving patient outcomes. This study will provide valuable insights into the effectiveness of such an approach in achieving glycemic control in people with type 2 diabetes on insulin therapy. By evaluating both clinical outcomes and patient and healthcare professionals' satisfaction, the study aims to contribute to the development of efficient, scalable telehealth solutions for diabetes care.

ClinicalTrials.gov NCT06185296. Registered on December 14, 2023.

Limited evidence exists to support any specific medication over others to prevent dementia in older patients with type 2 diabetes (T2D). We investigated whether treatment with sodium-glucose cotransporter 2 (SGLT-2) inhibitors is associated with a lower risk of incident dementia and all-cause mortality, relative to dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RA).

In this retrospective, active-comparator cohort study, we used data from the TriNetX electronic health records network. Our primary cohort comprised patients with T2D aged ≥50 years, registered between January 2012 and December 2022. Patients with a history of dementia were excluded. We used Kaplan-Meier survival analysis to estimate the incidence of dementia and all-cause mortality in our cohort after they had used glucose-lowering drugs for at least 12 months. Propensity score matching was performed to balance the SGLT-2 inhibitor, DPP-4 inhibitor and GLP-1 RA cohorts. Subgroup analyses for sex and age were also conducted.

Our first cohort comprised 193 948 patients treated with metformin and SGLT-2 inhibitors and an equal number of patients treated with metformin and DPP-4 inhibitors. In this cohort, the risk of dementia and all-cause mortality was lower in patients treated with SGLT-2 inhibitors than in those treated with DPP-4 inhibitors (hazard ratio [HR]: 0.62, 95% confidence interval [CI]: 0.59-0.65, for dementia; HR: 0.54, 95% CI: 0.52-0.56, for all-cause mortality). Our second cohort comprised 165 566 patients treated with metformin and SGLT-2 inhibitors and an equal number of patients treated with metformin and GLP-1 RAs. In this cohort, the risk of dementia and all-cause mortality was lower in those treated with SGLT-2 inhibitors than in those treated with GLP-1 RAs (HR: 0.92, 95% CI: 0.87-0.98, for dementia; HR: 0.88, 95% CI: 0.85-0.91, for all-cause mortality).

The use of SGLT-2 inhibitor was associated with a lower risk of incident dementia and all-cause mortality in older adults with T2D compared to DPP-4 inhibitor and GLP-1 RA.

Diabetes mellitus (DM) and heart failure (HF) share vascular, skeletal and metabolic abnormalities that can reduce exercise capacity. We investigated whether exercise capacity differ in patients with type 2 DM compared to those without DM with HF of similar severity.

The Studies Investigating Co-morbidities Aggravating HF (SICA-HF) prospectively enrolled 615 patients with chronic HF, 259 (42.1 %) of whom had DM. We assembled a propensity score-matched cohort of 231 pairs of patients with HF with or without DM who were balanced on age, sex and variables reflecting HF severity. Patients with DM had lower median peak VO2 (15.7 [13.0-19.1] vs. 17.3 [14.1-21.0] ml/min/kg; p = 0.005). Forearm blood flow reserve (per 1 ml/min/100 ml increase) was associated with lower exercise capacity (peak VO2 ≤ 16.6 ml/min/kg) in patients with DM (OR, 0.92; 95 % CI, (0.85-0.98; p = 0.014), but not in those without DM (OR, 0.98; 95 % CI, 0.93-1.02). A similar heterogeneity was also observed for HDL cholesterol.

Diabetes is associated with a reduced exercise capacity in patients with HF. Most predictors of lower exercise capacity in HF are similar regardless of DM except impaired vascular function and lower HDL cholesterol which predict lower exercise capacity only in those with DM.

Type 2 diabetes (T2D) is a chronic condition that requires not only a team-based approach but also substantial self-management by those affected. Patient-clinician barriers such as lack of educational resources, hesitancy in initiation of therapy, concerns over treatment-related side effects, frequency of dosing, and the establishment of treatment goals, can prevent a patient from achieving optimal glycemic management. Recently, advances in diabetes technology and insulin formulations have helped to address some of these concerns. Insulin icodec, the first once-weekly basal insulin analog, has demonstrated efficacy and safety comparable to traditional basal insulin formulations. Since clinicians and patients may benefit from a once-weekly therapy, this review sought to evaluate the potential clinical implications of insulin icodec. A literature search was performed using PubMed, Google Scholar, and ClinicalTrials.gov up to 31 January 2024. Key search terms such as once-weekly basal insulin, icodec, and ONWARDS were utilized to compile relevant publications. Further, studies involving patients living with T2D on once-weekly insulin icodec compared with once-daily basal insulin were considered for this review. Findings from this review suggest insulin icodec can offer a reduced dosing frequency that may improve medication adherence, provide effective glycemic management, and a comparable safety profile to existing basal insulins. In summary, insulin icodec may help to remove patient-clinician barriers associated with suboptimal glycemic management with its once-weekly dosing schedule. Clinicians can further support a patient's ability to self-manage the disease through continued monitoring and guidance on the use of icodec.

Diabetes is unique among chronic diseases because clinical outcomes are intimately tied to how the person living with diabetes reacts to and implements treatment recommendations. It is further characterised by widespread social stigma, judgement and paternalism. This physical, social and psychological burden collectively influences self-management behaviours. It is widely recognised that the individual's perspective about the impact of trying to manage the disease and the burden that self-management confers must be addressed to achieve optimal health outcomes. Standardised, rigorous assessment of mental and behavioural health status, in interaction with physical health outcomes is crucial to aid understanding of person-reported outcomes (PROs). Whilst tempting to conceptualise PROs as an issue of perceived quality of life (QoL), in fact health-related QoL is multi-dimensional and covers indicators of physical or functional health status, psychological and social well-being. This complexity is illuminated by the large number of person reported outcome measures (PROMs) that have been developed across multiple psychosocial domains. Often measures are used inappropriately or because they have been used in the scientific literature rather than based on methodological or outcome assessment rigour. Given the broad nature of psychosocial functioning/mental health, it is important to broadly define PROs that are evaluated in the context of therapeutic interventions, real-life and observational studies. This report summarises the central themes and lessons derived in the assessment and use of PROMs amongst adults with diabetes. Effective assessment of PROMs routinely in clinical research is crucial to understanding the true impact of any intervention. Selecting appropriate measures, relevant to the specific factors of PROs important in the research study will provide valuable data alongside physical health data.

Diabetic retinopathy (DR) is the leading cause of blindness among the working-age population. Although controlling blood glucose levels effectively reduces the incidence and development of DR to less than 50%, there are currently no diagnostic biomarkers or effective treatments for DR development in glucose-well-controlled diabetic patients (GW-DR). In this study, we established a prospective GW-DR cohort by strictly adhering to glycemic control guidelines and maintaining regular retinal examinations over a median 2-year follow-up period. The discovery cohort encompassed 71 individuals selected from a pool of 292 recruited diabetic patients at baseline, all of whom consistently maintained hemoglobin A1c (HbA1c) levels below 7% without experiencing hypoglycemia. Within this cohort of 71 individuals, 21 subsequently experienced new-onset GW-DR, resulting in an incidence rate of 29.6%. In the validation cohort, we also observed a significant GW-DR incidence rate of 17.9%. Employing targeted metabolomics, we investigated the metabolic characteristics of serum in GW-DR, revealing a significant association between lower levels of ethanolamine and GW-DR risk. This association was corroborated in the validation cohort, exhibiting superior diagnostic performance in distinguishing GW-DR from diabetes compared to the conventional risk factor HbA1c, with AUCs of 0.954 versus 0.506 and 0.906 versus 0.521 in the discovery and validation cohorts, respectively. Furthermore, in a streptozotocin (STZ)-induced diabetic rat model, ethanolamine attenuated diabetic retinal inflammation, accompanied by suppression of microglial diacylglycerol (DAG)-dependent protein kinase C (PKC) pathway activation. In conclusion, we propose that ethanolamine is a potential biomarker and represents a viable biomarker-based therapeutic option for GW-DR.

Silibinin has considerable therapeutic potential for the treatment of diabetes through anti-inflammatory, antioxidant, and immunomodulatory properties. However, the therapeutic application of silibinin is quite limited due to its poor bioavailability. In the present study, an attempt was made to improve the antidiabetic efficacy of silibinin by its encapsulation in liposomal vesicles. The liposomes with a high encapsulation efficiency of silibinin (96%) and a zeta potential of -26.2 ± 0.6 mV were developed and studied using nicotinamide/streptozotocin-induced diabetic rats. Administration of silibinin-loaded liposomes to diabetic rats lowered glucose levels, increased insulin levels, and improved pancreatic islet architecture. The anti-inflammatory effect of silibinin-loaded liposomes was demonstrated by a decrease in serum C-reactive protein (CRP) levels and a reduced deposition of collagen fibers in the islets of diabetic rats. Furthermore, silibinin-loaded liposomes were more efficient in lowering glucose, alanine transaminase, triglyceride, and creatinine levels in diabetic rats than pure silibinin. In addition, silibinin-loaded liposomes had a significantly better effect on beta-cell mass and Glut2 glucose receptor distribution in diabetic islets than pure silibinin. The present results clearly show that liposome encapsulation of silibinin enhances its antidiabetic efficacy, which may contribute to the therapeutic benefit of silibinin in the treatment of diabetes and its complications.

Aging is one of the most important public health issues. Previous studies on the factors affecting aging focused on genetics and lifestyle, but the association between polycyclic aromatic hydrocarbons (PAHs) and aging is still unclear.

This study utilized data from the National Health and Nutrition Examination Survey (NHANES) 2003-2010. A total of 8,100 participants was used to construct the biological age predictors by using recent advanced algorithms Klemera-Doubal method (KDM) and Mahalanobis distance. Two biological aging indexes, recorded as KDM-BA acceleration and PhenoAge acceleration, were used to investigate the relationship between single PAHs and biological age using a multiple linear regression analysis, and a weighted quantile sum (WQS) model was constructed to explore the mixed effects of PAHs on biological age. Finally, we constructed the restricted cubic spline (RCS) model to assess the non-linear relationship between PAHs and biological age.

Exposure to PAHs was associated with PhenoAge acceleration. Each unit increase in the log10-transformed level of 1-naphthol, 2-naphthol, and 2-fluorene was associated with a 0.173 (95% CI: 0.085, 0.261), 0.310 (95% CI: 0.182, 0.438), and 0.454 (95% CI: 0.309, 0.598) -year increase in PhenoAge acceleration, respectively (all corrected P < 0.05). The urinary PAH mixture was relevant to KDM-BA acceleration (β = 0.13, 95% CI: 0, 0.26, P = 0.048) and PhenoAge acceleration (β = 0.59, 95% CI: 0.47, 0.70, P < 0.001), and 2-naphthol had the highest weight in the weighted quantile sum (WQS) regression. The RCS analyses showed a non-linear association between 2-naphthol and 2-fluorene with KDM-BA acceleration (all P < 0.05) in addition to a non-linear association between 1-naphthol, 2-naphthol, 3-fluorene, 2-fluorene, and 1-pyrene with PhenoAge acceleration (all P < 0.05).

Exposure to mixed PAHs is associated with increased aging, with 2-naphthol being a key component of PAHs associated with aging. This study has identified risk factors in terms of PAH components for aging.

To investigate the efficacy and safety of pioglitazone compared to placebo when added to metformin plus dapagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, for patients with type 2 diabetes mellitus (T2DM).

In a multicentre study, with a randomized, double-blind, placebo-controlled design, 249 Korean patients with T2DM suboptimally managed on metformin and dapagliflozin were assigned to receive either pioglitazone (15 mg daily) or placebo for 24 weeks, followed by a 24-week pioglitazone extension. Primary outcomes included changes in glycated haemoglobin (HbA1c), with secondary outcomes assessing insulin resistance, adiponectin levels, lipid profiles, liver enzymes, body weight and waist circumference.

Pioglitazone administration resulted in a significant reduction in HbA1c levels (from 7.80% ± 0.72% to 7.27% ± 0.82%) compared with placebo (from 7.79% ± 0.76% to 7.69% ± 0.86%, corrected mean difference: -0.42% ± 0.08%; p < 0.01) at 24 weeks. Additional benefits from pioglitazone treatment included enhanced insulin sensitivity, increased adiponectin levels, raised high-density lipoprotein cholesterol levels and reduced liver enzyme levels, resulting in improvement in nonalcoholic fatty liver disease liver fat score. Despite no serious adverse events in either group, pioglitazone therapy was modestly but significantly associated with weight gain and increased waist circumference.

Adjunctive pioglitazone treatment in T2DM inadequately controlled with metformin and dapagliflozin demonstrates considerable glycaemic improvement, metabolic benefits, and a low risk of hypoglycaemia. These advantages must be weighed against the potential for weight gain and increased waist circumference.

We aimed to report the latest and largest pooled analyses and evidence updates to assess the effectiveness of telemedicine interventions for self-management (DSM) in patients with type 2 diabetes mellitus (T2DM).

A systematic literature search was conducted using PubMed, Cochrane, Embase, and Web of Science in December 2023. We included randomized controlled trials (RCTs) of adults (≥18 years of age) diagnosed with T2DM where the intervention was the application of telemedicine. The Cochrane Risk of Bias Assessment was used to evaluate quality. The study's main outcome indicators were glycosylated hemoglobin (HbA1c) and diabetes self-management (DSM) capacity.

A total of 17 eligible articles, comprising 20 studies and 1,456 patients (734 in the intervention group and 722 in the control group), were included in the evidence synthesis. The baseline characteristics of both groups were similar in all outcomes. Comprehensive analyses showed post-intervention decreases in HbA1c, 2-h postprandial glucose, systolic and diastolic blood pressure, increases in Diabetes Self- Care activities, DSM competencies based on dietary and medication adherence, and improvements in overall DSM scores, all of which were statistically significant. While no statistically significant differences were observed in body mass index, lipids, and other DSM dimensions. Based on subgroup analyses, app-based experimental interventions targeting under 60 years old populations in Asia and North America were found to be more effective and less heterogeneity in the short term (<6 months of intervention).

Telemedicine interventions may assist patients with T2DM in enhancing their DSM and improving their HbA1c levels. Clinician can use various telemedicine interventions to enhance DSM in T2DM patients, considering local circumstances.

https://www.crd.york.ac.uk/PROSPERO/, CRD42024508522.

A precision medicine approach in type 2 diabetes could enhance targeting specific glucose-lowering therapies to individual patients most likely to benefit. We aimed to use the recently developed Bayesian causal forest (BCF) method to develop and validate an individualised treatment selection algorithm for two major type 2 diabetes drug classes, sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1-RA).

We designed a predictive algorithm using BCF to estimate individual-level conditional average treatment effects for 12-month glycaemic outcome (HbA1c) between SGLT2i and GLP1-RA, based on routine clinical features of 46,394 people with type 2 diabetes in primary care in England (Clinical Practice Research Datalink; 27,319 for model development, 19,075 for hold-out validation), with additional external validation in 2252 people with type 2 diabetes from Scotland (SCI-Diabetes [Tayside & Fife]). Differences in glycaemic outcome with GLP1-RA by sex seen in clinical data were replicated in clinical trial data (HARMONY programme: liraglutide [n=389] and albiglutide [n=1682]). As secondary outcomes, we evaluated the impacts of targeting therapy based on glycaemic response on weight change, tolerability and longer-term risk of new-onset microvascular complications, macrovascular complications and adverse kidney events.

Model development identified marked heterogeneity in glycaemic response, with 4787 (17.5%) of the development cohort having a predicted HbA1c benefit >3 mmol/mol (>0.3%) with SGLT2i over GLP1-RA and 5551 (20.3%) having a predicted HbA1c benefit >3 mmol/mol with GLP1-RA over SGLT2i. Calibration was good in hold-back validation, and external validation in an independent Scottish dataset identified clear differences in glycaemic outcomes between those predicted to benefit from each therapy. Sex, with women markedly more responsive to GLP1-RA, was identified as a major treatment effect modifier in both the UK observational datasets and in clinical trial data: HARMONY-7 liraglutide (GLP1-RA): 4.4 mmol/mol (95% credible interval [95% CrI] 2.2, 6.3) (0.4% [95% CrI 0.2, 0.6]) greater response in women than men. Targeting the two therapies based on predicted glycaemic response was also associated with improvements in short-term tolerability and long-term risk of new-onset microvascular complications.

Precision medicine approaches can facilitate effective individualised treatment choice between SGLT2i and GLP1-RA therapies, and the use of routinely collected clinical features for treatment selection could support low-cost deployment in many countries.

To assess and compare the metabolic and vascular effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT-2i) and dipeptidyl peptidase-4 inhibitors (DPP-4i) in the clinical practice of patients with type 2 diabetes in Italy.

GIOIA is a 2-year prospective, multicentre, quasi-experimental study that enrolled patients with type 2 diabetes initiating SGLT-2i or DPP-4i for inadequate glycaemic control [glycated haemoglobin (HbA1c) >7%] between March 2018 and March 2021. The primary endpoints were changes in markers of organ damage [carotid intima-media thickness (CIMT), albuminuria, myocardial function] and HbA1c from baseline to year 2.

In total, 1150 patients were enrolled in the study (SGLT-2i n = 580, DPP-4i n = 570). Patients initiated on SGLT-2i were younger (about 6 years) and heavier (about 11 kg), had higher HbA1c level (1% more), more albuminuria and cardiovascular events (16% more) than patients initiated on DPP-4i. CIMT and echocardiographic parameters were not significantly different. Propensity score matching yielded two groups, each consisting of 155 patients with diabetes with similar baseline characteristics. Despite a significant similar reduction in HbA1c levels in both groups (-0.8%), more patients on SGLT-2i had regression of CIMT and albuminuria (22% and 10%, respectively, p < .001 vs. DPP-4i); more patients on DPP-4i had progression of CIMT and albuminuria (23% and 28%, respectively, p < .001 vs. SGLT-2i). Left ventricular ejection fraction improved slightly (3%, p = .043) on SGLT-2i only.

In a real-world setting, both SGLT-2i and DPP-4i improve glycaemic control persisting after 2 years of treatment, with a robust effect on both CIMT and albuminuria regression for SGLT-2i as compared with DPP-4i in the propensity score matching.

Genetic variants contribute to differential responses to non-insulin antidiabetic drugs (NIADs), and consequently to variable plasma glucose control. Optimal control of plasma glucose is paramount to minimizing type 2 diabetes-related long-term complications. India's distinct genetic architecture and its exploding burden of type 2 diabetes warrants a population-specific survey of NIAD-associated pharmacogenetic (PGx) variants. The recent availability of large-scale whole genomes from the Indian population provides a unique opportunity to generate a population-specific map of NIAD-associated PGx variants.

We mined 1029 Indian whole genomes for PGx variants, drug-drug interaction (DDI) and drug-drug-gene interactions (DDGI) associated with 44 NIADs. Population-wise allele frequencies were estimated and compared using Fisher's exact test.

Overall, we found 76 known and 52 predicted deleterious common PGx variants associated with response to type 2 diabetes therapy among Indians. We report remarkable interethnic differences in the relative cumulative counts of decreased and increased response-associated alleles across NIAD classes. Indians and South Asians showed a significant excess of decreased metformin response-associated alleles compared with other global populations. Network analysis of shared PGx genes predicts high DDI risk during coadministration of NIADs with other metabolic disease drugs. We also predict an increased CYP2C19-mediated DDGI risk for CYP3A4/3A5-metabolized NIADs, saxagliptin, linagliptin and glyburide when coadministered with proton-pump inhibitors (PPIs).

Indians and South Asians have a distinct PGx profile for antidiabetes drugs, marked by an excess of poor treatment response-associated alleles for various NIAD classes. This suggests the possibility of a population-specific reduced drug response in atleast some NIADs. In addition, our findings provide an actionable resource for accelerating future diabetes PGx studies in Indians and South Asians and reconsidering NIAD dosing guidelines to ensure maximum efficacy and safety in the population.

Randomized controlled trials (RCTs) and real-world evidence (RWE) studies are crucial and complementary in generating clinical evidence. RCTs provide controlled settings to validate the clinical effect of specific drugs or medical devices, while RWE integrates extrinsic factors, encompassing external influences affecting real-world scenarios, thus challenging RCT results in practical applications. In this study, we explore the impact of extrinsic factors on RWE outcomes, focusing on "dark data," which refers to data collected but not used or excluded from the analyses. Dark data can arise in many ways during research process, from selecting study samples to data collection and analysis. However, even unused or unanalyzed dark data hold potential insights, providing a comprehensive view of clinical contexts. Extrinsic factors lead to divergent RWE outcomes that could differ from RCTs beyond statistical correction's scope. Two main types of dark data exist: "known-unknown" and "unknown-unknown." The distinction between these dark data types highlights RWE's complexity. The transformation of unknown into known depends on data literacy-powerful utilization capabilities that can be interpreted based on medical expertise. Shifting the focus to excluded subjects or unused data in real-world contexts reveals unexplored potential. Understanding the significance of dark data is vital in reflecting the complexity of clinical settings. Connecting RCTs and RWEs requires medical data literacy, enabling clinicians to decipher meaningful insights. In the big data and artificial intelligence era, medical staff must navigate data complexities while promoting the core role of medicine. Prepared clinicians will lead this transformative journey, ensuring data value shapes the medical landscape.

Awareness of diabetes as a major risk factor for cardiovascular disease (CVD) may enhance uptake of screening for diabetes and primary prevention of CVD.

The American Heart Association conducted an online survey in 50 countries. The main outcome of this study was the proportion of individuals in each country who recognized diabetes as a CVD risk factor. We also examined variation by sex, age, geographic region, and country-level economic development.

Among 48,988 respondents, 15,747 (32.1%) identified diabetes as a major CVD risk factor. Awareness was similar among men and women, but increased with age, and was greater in high-income than in middle-income countries.

Two-thirds of adults in surveyed countries did not recognize diabetes as a major CVD risk factor. Given the increasing global burden of diabetes and CVD, this finding underscores the need for concerted efforts to raise public health awareness.

Diabetes mellitus (DM) poses a significant global health burden, with hyperglycemia being a primary contributor to complications and high morbidity associated with this disorder. Existing glucose management strategies have shown suboptimal effectiveness, necessitating alternative approaches. In this study, we explored the role of high mobility group box 1 (HMGB1) in hyperglycemia, a protein implicated in initiating inflammation and strongly correlated with DM onset and progression. We hypothesized that HMGB1 knockdown will mitigate hyperglycemia severity and enhance glucose tolerance. To test this hypothesis, we utilized a novel inducible HMGB1 knockout (iHMGB1 KO) mouse model exhibiting systemic HMGB1 knockdown. Hyperglycemic phenotype was induced using low dose streptozotocin (STZ) injections, followed by longitudinal glucose measurements and oral glucose tolerance tests to evaluate the effect of HMGB1 knockdown on glucose metabolism. Our findings showed a substantial reduction in glucose levels and enhanced glucose tolerance in HMGB1 knockdown mice. Additionally, we performed RNA sequencing analyses, which identified potential alternations in genes and molecular pathways within the liver and skeletal muscle tissue that may account for the in vivo phenotypic changes observed in hyperglycemic mice following HMGB1 knockdown. In conclusion, our present study delivers the first direct evidence of a causal relationship between systemic HMGB1 knockdown and hyperglycemia in vivo, an association that had remained unexamined prior to this research. This discovery positions HMGB1 knockdown as a potentially efficacious therapeutic target for addressing hyperglycemia and, by extension, the DM epidemic. Furthermore, we have revealed potential underlying mechanisms, establishing the essential groundwork for subsequent in-depth mechanistic investigations focused on further elucidating and harnessing the promising therapeutic potential of HMGB1 in DM management.

Cardiovascular complications and renal disease is the growing cause of mortality in patients with diabetes. The subversive complications of diabetes such as hyperglycemia, hyperlipidemia and insulin resistance lead to an increase in the risk of myocardial infarction (MI), stroke, heart failure (HF) as well as chronic kidney disease (CKD). Among the commercially available anti-hyperglycemic agents, incretin-based medications appear to be safe and effective in the treatment of type 2 diabetes mellitus (T2DM) and associated cardiovascular and renal disease. Glucagon-like peptide 1 receptor agonists (GLP-1RAs) have been shown to be fruitful in reducing HbA1c, blood glucose, lipid profile, and body weight in diabetic patients. Several preclinical and clinical studies revealed the safety, efficacy, and preventive advantages of GLP-1RAs against diabetes- induced cardiovascular and kidney disease. Data from cardio-renal outcome trials had highlighted that GLP-1RAs protected people with established CKD from significant cardiovascular disease, lowered the likelihood of hospitalization for heart failure (HHF), and lowered all-cause mortality. They also had a positive effect on people with end-stage renal disease (ESRD) and CKD. Beside clinical outcomes, GLP-1RAs reduced oxidative stress, inflammation, fibrosis, and improved lipid profile pre-clinically in diabetic models of cardiomyopathy and nephropathy that demonstrated the cardio-protective and reno-protective effect of GLP-1RAs. In this review, we have focused on the recent clinical and preclinical outcomes of GLP-1RAs as cardio-protective and reno-protective agents as GLP-1RAs medications have been demonstrated to be more effective in treating T2DM and diabetes-induced cardiovascular and renal disease than currently available treatments in clinics, without inducing hypoglycemia or weight gain.

This article describes a program through which interactions every 2-3 weeks between patients and primary care clinicians (PCCs), with recommendations based on analysis of remote glucose monitoring by computerized insulin dose adjustment algorithms, significantly improved diabetes control. Insulin doses increased by 30% in the majority of patients. A sizeable minority (36%) had a decrease or no increase in insulin doses, but still showed an improvement in diabetes control. Frequent interactions allowed PCCs the opportunity to recognize and address medication nonadherence.

Patient- and physician-associated barriers impact the effectiveness of basal insulin (BI) titration in the management of type 2 diabetes (T2D). We evaluated the experiences of patients with T2D and physicians with BI titration education.

In this observational, cross-sectional study, patients with T2D and physicians treating patients with T2D were identified by claims in the Optum Research Database and were invited to complete a survey. Eligible patients had 12 months of continuous health-plan enrolment with medical and pharmacy benefits during the baseline period, and recent initiation of BI therapy. Eligible physicians had initiated BI for ≥1 eligible patient with T2D during the past 6 months.

In total, 416 patients and 386 physicians completed the survey. Ninety per cent of physicians reported treating ≥50 patients with T2D; 66% treated ≥25% of patients with BI. Whereas 74% of patients reported that BI titration was explained to them by a physician, 96% of physicians reported doing so. Furthermore, 20% of patients stated they were offered educational materials whereas 56% of physicians reported having provided materials. Physicians had higher expectations of glycaemic target achievement than were seen in the patient survey; their main concern was the patients' ability to titrate accurately (79%).

There is a marked difference in patients' and physicians' experiences of BI titration education. Novel tools and strategies are required to enable effective BI titration, with more educational resources at the outset, and ongoing access to tools that provide clear, simple direction for self-titration with less reliance on physicians/health care providers.

Glucagon-like peptide-1 receptor agonist (GLP-1 RA) is used to treat obesity or type 2 diabetes mellitus (DM). We compared weight loss and side-effects between patients with and without DM using GLP-1 RA.

This was a retrospective cohort study based on electronic medical records. Patients were categorized into three groups: liraglutide without DM (LiRa_NL), liraglutide with DM (LiRa_DM), and lixisenatide with DM (LiXi_DM). Six-month outcomes were evaluated for weight loss, side-effect types, and onset discontinuation of GLP-1 RA.

We enrolled 356 (190 LiRa_NL, 95 LiRa_DM, and 71 LiXi_DM) patients (women, 72.5 %; mean age, 43.7 ± 12.7 years; mean body mass index, 30.7 ± 5.2 kg/m2). The mean glycated hemoglobin (HbA1c) participants were 7.7 ± 2.1 %. Average weight loss was 2.9 ± 0.3 kg. The change in HbA1c was lower in the LiXi_DM group than in the LiRa_DM group (- 1.1 ± 0.2 % vs. - 0.4 ± 0.1 %, P < 0.05). The LiRa_DM group showed a more effective weight loss (- 3.0 ± 0.4 kg) than the LiXi_DM group (- 0.9 ± 0.4 kg) (P < 0.05). Approximately 30 % of the patients reported experiencing side-effects, with gastrointestinal side-effects being the most frequent (20.5 %). The median side-effect onset was 1.9 ± 0.1 months from first treatment. The rate of GLP-1 RA discontinuation was 72.8 %. Discontinuation rates due to side-effects were 75.7 %, 68.9 %, and 64.4 % in the LiRa_NL, LiRa_DM, and LiXi_DM groups, respectively.

The LiRa_NL group showed the most weight loss, although the discontinuation rate was high. Most side-effects occurred at 1-2 months. When prescribing GLP-1 RA, education concerning side-effects and discontinuation is needed to enhance treatment adherence.

To evaluate the real-life effectiveness and safety of Chinese patients with type 2 diabetes mellitus (T2DM) receiving hydrogen inhalation (HI) treatment as a supplementary treatment.

This retrospective, multicenter, observational 6-months clinical study included T2DM patients maintaining HI, visited at 4 time points. The primary outcome is the mean change in glycated hemoglobin (HbA1c) at the end of the study compared to baseline. The secondary outcome is analyzing the mean change of fasting plasma glucose (FPG), weight, lipid profile, insulin dose and homeostasis model assessment. Linear regression and logistics regression are applied to evaluate the effect of HI after the treatment.

Of the 431 patients comprised, it is observed a significant decrease in HbA1c level (9.04±0.82% at baseline to 8.30±0.99% and 8.00±0.80% at the end, p<0.001), FPG (165.6±40.2 mg/dL at baseline to 157.1±36.3mg/dL and 143.6±32.3mg/dL at the end, p<0.001), weight (74.7±7.1kg at baseline to 74.8±10.0kg and 73.6±8.1kg at the end, p<0.001), insulin dose (49.3±10.8U/d at baseline to 46.7±8.0U/d and 45.2±8.7U/d, p<0.001). The individuals in subgroup with higher baseline HbA1c and longer daily HI time duration gain greater HbA1c decrease after 6 months. Linear regression shows that higher baseline HbA1c level and shorter diabetes duration are significantly in relation to greater HbA1c reduction. Logistics regression reveals that lower weight is associated with a higher possibility of reaching HbA1c<7%. The most common adverse event is hypoglycemia.

HI therapy significantly improves glycemic control, weight, insulin dose, lipid metabolism, β-cell function and insulin resistance of patients with type 2 diabetes after 6 months. Higher baseline HbA1c level and shorter diabetes duration is related to greater clinical response to HI.

This paper presented the methodology and main findings of a population-based survey to determine diabetes care status among type 2 diabetic subjects in Iran. The current study assessed treatment goal achievements in type 2 diabetics, diabetes care service utilization, prevalence of diabetes complications, and psychological effects of diabetes in a representative sample of Iranian population in urban and rural areas.

This nationwide study was conducted between 2018 and 2020 as the observational survey entitled "Diabetes Care (DiaCare)". We studied a representative sample of participants with type 2 diabetes, aged 35-75 years, living in urban and rural areas in all thirty- one provinces of Iran. Data were collected by an interviewer in a form of a questionnaire that includes demographic and socioeconomic status, family and drug history, lifestyle, and self-reported psychological status according to a Patient's Health Questionnaire (PHQ). Management goal achievements, diabetes care service utilization, diabetes complications and psychological effects of diabetes were also assessed. Physical measurements were measured based on standard protocol. Fasting blood glucose (FBG), HbA1c, lipid profile, and also urine albumin to creatinine ratio were obtained from all participants of the study.

Overall, 13,334 people with type 2 diabetes in 31 provinces of Iran completed the survey (response rate: 99.6%). In total 13,321 participants, 6683(50.17%) women and 6638(49.83%) men were included in our analysis. Thirteen recruited patients refused after the consenting process and did not respond. The mean age (SD) of total participants was 54.86 ± 9.44 years and 71.50% were from the urban areas. 13.66% of diabetic patients had achieved the triple target of management [controlled HbA1c, blood pressure, and Low-Density Lipoprotein-Cholesterol (LDL-C)] in the whole country. While 28.74% of people had controlled HbA1c and 33.40% of them had controlled FBG. Diabetic subjects living in rural areas had less controlled HbA1c (23.93 vs. 29.48), controlled FBG (29.50 vs. 34.20) and controlled triple targets (10.45 vs. 14.32) than those living in urban areas. Diabetic neuropathy and diabetic foot were more common in women than men, while end-stage of renal disease (ESRD) was more common in men than women.

This population-based study provided representative information about diabetes care in Iran. The high prevalence of diabetes and low proportion of diabetes control in Iran implies that it is necessary to identify factors associated with poor treatment goal achievements. Besides, general improvements in management and care of diabetes are mandatory.

Previous systematic reviews have aimed to clarify the effect of telemedicine on diabetes. However, such reviews often have a narrow focus, which calls for a more comprehensive systematic review within the field. Hence, the objective of the present systematic review, meta-analysis, and meta-regression is to evaluate the effectiveness of telemedicine solutions versus any comparator without the use of telemedicine on diabetes-related outcomes among adult patients with type 2 diabetes (T2D).

This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We considered telemedicine randomized controlled trials (RCT) including adults (≥18 years) diagnosed with T2D. Change in glycated hemoglobin (HbA1c, %) was the primary outcome. PubMed, EMBASE, and the Cochrane Library Central Register of Controlled Trials (CENTRAL) were searched on October 14, 2020. An overall treatment effect was estimated using a meta-analysis performed on the pool of included studies based on the mean difference (MD). The revised Cochrane risk-of-bias tool was applied and the certainty of evidence was graded using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach.

The final sample of papers included a total of 246, of which 168 had sufficient information to calculate the effect of HbA1c%. The results favored telemedicine, with an MD of -0.415% (95% confidence interval [CI] = -0.482% to -0.348%). The heterogeneity was great (I2 = 93.05%). A monitoring component gave rise to the higher effects of telemedicine.

In conclusion, telemedicine may serve as a valuable supplement to usual care for patients with T2D. The inclusion of a telemonitoring component seems to increase the effect of telemedicine.

Our objective was to evaluate the association between patient profiles and sustained diabetes management (SDM) among patients with type 2 diabetes.

We collected HbA_1c values recorded from 2014 through 2020 for 570 patients in a hospital in Taipei, Taiwan, and calculated a standard level based on an HbA_1c level less than 7.0% to determine SDM. We used patients' self-reported data on diabetes self-care behaviors to construct profiles. We used 8 survey items to perform a latent profile analysis with 3 groups (poor management, medication adherence, and good management). After adjusting for other determining factors, we used multiple regression analysis to explore the relationship between patient profiles and SDM.

The good management group demonstrated better SDM than the poor management group (β = 0.183; P = .003). Using the most recent HbA_1c value and the 7-year average of HbA_1c values as the outcome, we found lower HbA_1c values in the good management group than in the poor management group (β = -0.216 [P = .01] and -0.217 [P = .008], respectively).

By using patient profiles, we confirmed a positive relationship between optimal patient behavior in self-care management and SDM. Patients with type 2 diabetes exhibited effective self-care management behavior and engaged in more health care activities, which may have led to better SDM. In promoting patient-centered care, using patient profiles and customized health education materials could improve diabetes care.

Tirzepatide, a novel dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist (RA), received regulatory approval from the U.S. Food and Drug Administration (13 May 2022) and marketing authorization from the European Commission (25 September 2022) for the improvement of glycemic control in adults with type 2 diabetes (T2D). In the phase 3 clinical development program (SURPASS), tirzepatide demonstrated superior glycemic and body weight control compared with placebo and active comparators across a spectrum of patients with T2D.

This review summarizes efficacy and safety results of the tirzepatide T2D phase 3 clinical trials that supported regulatory approvals. Additionally, it discusses a meta-analysis assessing tirzepatide cardiovascular (CV) safety, and provides a brief overview of ongoing late-stage clinical trials in patients with T2D. Information in this review was acquired from peer-reviewed published trials, ClinicalTrials.gov, and the manufacturer's website.

Based on phase 3 clinical trial data, tirzepatide is the most potent glucose and body weight lowering agent available for the management of T2D. The potential for tirzepatide to improve CV outcomes is currently being assessed in a CV outcomes trial (SURPASS CVOT). Results of this trial are highly anticipated and expected in 2024.

The ultimate purpose of diabetes care is achieving the outcomes that patients regard as important throughout the life course. Despite advances in pharmaceuticals, nutraceuticals, psychoeducational programs, information technologies, and digital health, the levels of treatment target achievement in people with diabetes mellitus (DM) have remained suboptimal. This clinical care of people with DM is highly challenging, complex, costly, and confounded for patients, physicians, and healthcare systems. One key underlying problem is clinical inertia in general and therapeutic inertia (TI) in particular. TI refers to healthcare providers' failure to modify therapy appropriately when treatment goals are not met. TI therefore relates to the prescribing decisions made by healthcare professionals, such as doctors, nurses, and pharmacists. The known causes of TI include factors at the level of the physician (50%), patient (30%), and health system (20%). Although TI is often multifactorial, the literature suggests that 28% of strategies are targeted at multiple levels of causes, 38% at the patient level, 26% at the healthcare professional level, and only 8% at the healthcare system level. The most effective interventions against TI are shorter intervals until revisit appointments and empowering nurses, diabetes educators, and pharmacists to review treatments and modify prescriptions.

To analyze the effectiveness and safety of hydrogen inhalation (HI) therapy as an adjunct treatment in Chinese type 2 diabetes mellitus (T2DM) patients in a real-life clinical setting.

This observational, non-interventional, retrospective, double-arm, 6-month clinical study included T2DM patients receiving conventional anti-diabetes medication with or without HI initiation from 2018 to 2021. Patients were assigned to the HI group or non-HI group (control group) after 1:1 propensity score matching (PSM). The mean change in glycated hemoglobin (HbA1c) after 6 months in different groups was evaluated primarily. The secondary outcome was composed of the mean change of fasting plasma glucose (FPG), weight, lipid profile, and homeostasis model assessment. Logistics regression was performed to evaluate the likelihood of reaching different HbA1c levels after 6-month treatment between the groups. Adverse event (AE) was also evaluated in patients of both groups.

In total, 1088 patients were selected into the analysis. Compared to the control group, subjects in HI group maintained greater improvement in the level of HbA1c (-0.94% vs -0.46%), FPG (-22.7 mg/dL vs -11.7 mg/dL), total cholesterol (-12.9 mg/dL vs -4.4 mg/dL), HOMA-IR (-0.76 vs -0.17) and HOMA-β (8.2% vs 1.98%) with all p< 0.001 post the treatment. Logistics regression revealed that the likelihood of reaching HbA1c< 7%, ≥ 7% to< 8% and > 1% reduction at the follow-up period was higher in the HI group, while patients in the control group were more likely to attain HbA1c ≥ 9%. Patients in HI group was observed a lower incidence of several AEs including hypoglycemia (2.0% vs 6.8%), vomiting (2.6% vs 7.4%), constipation (1.7% vs 4.4%) and giddiness (3.3% vs 6.3%) with significance in comparison to the control group.

HI as an adjunct therapy ameliorates glycemic control, lipid metabolism, insulin resistance and AE incidence of T2DM patients after 6-month treatment, presenting a noteworthy inspiration to existing clinical diabetic treatment.