Diabetes is a common condition with a dismal prognosis. According to the International Diabetes Federation, 537 million people worldwide have diabetes. Cardiovascular disorders (CVD) are the major cause of death globally. Diabetes mellitus type 2 (T2DM) increases the risk of CVD. Since 2008, the FDA has required all new antihyperglycemic treatments to show no increased CV risk. Years of glucocentric diabetic therapy have left many patients on medicines with no known CV benefit. GLP-1 receptor agonists (GLP-1RAs) are excellent glucose-lowering medicines with little risk of hypoglycaemia, CVD and weight loss. GLP-1RAs may also delay renal disease development. As an adjunct to metformin or ongoing therapy, GLP1RAs or sodium-glucose cotransporter-2 inhibitors are recommended by the American Diabetes Association and the European Association for the Study of Diabetes (EASD). Thus, this review summarises GLP-1RA and their significance in the paradigm shift in diabetes care recommendations from glucocentric to gluco-cardiocentric.

Objectives Sodium-glucose cotransporter-2 (SGLT-2) inhibitors and dipeptidyl peptidase IV (DPP-IV) inhibitors are recommended as preferred add-on oral antidiabetic drugs (OADs) after metformin among type 2 diabetes mellitus (T2DM) patients with atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), and chronic kidney disease (CKD). They are generally many folds costlier than other OADs. This is a simulatory analysis to assess the incremental cost escalation and risk reduction with their hypothetical substitution/addition in prescriptions of high-risk patients. Methods A simple simulation of cost-effectiveness analysis was performed using prescriptions of T2DM patients with established cardiovascular (CV) or renal disease or high-risk factors. SGLT-2 and DPP-IV inhibitors with proven benefits/safety were substituted or added in place of other OADs. Increments in treatment costs were calculated, and the anticipated decrease in hazards was extrapolated from cardiovascular outcome trials (CVOTs) and real-world studies. The incremental cost-effectiveness ratios (ICERs) were calculated. Results Prescriptions of 351 patients with a mean age of 58.04 ± 8.67 years were analyzed. The median annual acquisition cost of drug therapy for diabetes per patient was found to be Indian national rupee (INR) 8,964.4 for the original prescriptions when calculated using median retail prices of drugs prescribed for diabetes. Upon substituting one of the SGLT-2 inhibitors for the other OADs in the regimen, the cost increased to INR 12,265 (increase by 36.8%) for dapagliflozin, and INR 26,718 and INR 29,419 (increase by ~200%), respectively, for canagliflozin and empagliflozin. Upon calculating the ICERs, additional cost to prevent one all-cause death with dapagliflozin substitution is INR 660,020-25,384,369; INR 2,223,326 with empagliflozin substitution and INR 8,069,818 with canagliflozin substitution. The ICER for prevention of hospitalization with HF with dapagliflozin substitution is INR 1,320,040-1,435,543; INR 4,010,706 with empagliflozin and INR 5,548,000 with canagliflozin. To prevent a three-point major adverse cardiac event (3P-MACE), INR 2,062,562 would be needed with dapagliflozin substitution, and INR 3,146,861 and INR 3,859,478 with empagliflozin and canagliflozin, respectively. Incremental costs for various outcomes were higher with the addition of SGLT-2 inhibitors and significantly more if substitution with sitagliptin/linagliptin was also done. The numbers needed to treat were calculated too and ranged from 35 to 1,831 for various outcomes and drugs. Conclusion While the recommendations for use of SGLT-2 and DPP-IV inhibitors are adequately backed by evidence from CVOTs and real-world data, the incremental costs per event reduction are quite high for most outcomes in the Indian context. Dapagliflozin, being available as cheaper generic versions, appears to be most effective for most outcomes. Interpretations are subjective in terms of value assigned for preventing a major event.

Type II Diabetes Mellitus (T2DM) is a serious public health issue, affecting the global population, particularly those living in low- and middle-income countries. Worldwide, the prevalence of T2DM ranges between 10.4% and 13.5%, depending on the domiciliary. T2DM negatively affects individuals\' quality of life and causes high economic burden due to the increasing cost of treatment and management of the disease. Risk factors associated with T2DMs include aging, lifestyle or behavior, genetics, and important biopsychological aspects, which are psychological stress and sleep deprivation. By understanding the associations of psychological stress and sleep deprivation, which contribute to pathophysiology of T2DM, policies, programs, and guidelines were developed in Malaysia to combat the issue among population at large. This narrative review examines 19 national public health policies, programs, and guidelines from the past 20 years in Malaysia that aimed to mitigate the negative health effects of psychological stress, sleep deprivation, and T2DM, both from the government and non-governmental organizations. Both psychological stress and sleep deprivation works independently or as combined effects in the pathophysiology of T2DM. Besides, in Malaysia, the government, in collaboration with non-governmental organizations, have been developing and implementing policies, programs, and guidelines to combat mental health and T2DM issues, targeted to population at large. Integration of digital technology, such as usage of social media for health promotion and dissemination of public health messages to the community and good governance from government were deemed important in the effective implementation of health policies and guidelines, resulting in better health outcome.

BACKGROUND: According to current guidelines, appropriate drug treatment is the backbone of the effective management of cardiovascular (CV) comorbidities in patients with type 2 diabetes mellitus (T2DM). The main objective of this study was to assess the degree of real-world adherence to these guideline recommendations and to identify whether poor guideline adherence is associated with worse clinical outcomes.
METHODS: In this retrospective German claims data analysis (AOK PLUS dataset), patients with T2DM with an incident diagnosis (index date) of ischemic stroke, myocardial infarction, heart failure or coronary artery disease were observed for 12 months between 1 January 2014 and 31 December 2017. We assessed guideline adherence per observed CV disease combination at three levels: \"green\" if patients received prescriptions of all recommended medications with > 185 defined daily doses (DDDs) per observed patient-year; \"yellow\" if patients received at least two prescriptions of at least one of the recommended medications; and \"red\" if patients did not receive at least two prescriptions of at least one of the recommended medications. The impact of the assignment of a patient to one of these three levels on all-cause mortality and CV risk was analyzed based on multivariable Cox regression analyses and reported as adjusted hazard ratios (HRs).
RESULTS: We identified 32,916 patients with T2DM with an incident CV comorbidity (mean age 75.0 years, 54.2% female, Charlson Comorbidity Index [CCI]: 5.5). Observed patients received at least 185 DDDs of the following medication classes in the 12 months before/after the index date: vitamin K antagonists (6%/6%); antiplatelet drugs (9%/27%); novel oral anticoagulants (3%/13%); diuretics (48%/54%); beta blockers (31%/35%); calcium-channel blockers (34%/32%); renin-angiotensin-aldosterone system inhibitors (69%/68%); and lipid-modifying agents (19%/37%). When post-index therapy was compared to guideline recommendations, the level of \"guideline adherence\" was classified as \"green\" for 14.4% of the patients, \"yellow\" for 75.2% and \"red\" for 10.5%. An assignment of \"red\" was associated with worse CV outcomes in all analyses. Regarding mortality, in addition to one additional year of age (hazard ratio [HR] 1.04), CCI (HR 1.17), use of insulins (HR 1.25), digitalis glycosides (HR 1.52) and diuretics (HR 1.32), non-adherence to guideline recommendations (\"red\": HR 6.79; \"yellow\": HR: 1.30) was a significant predictor for early death, while female gender (HR 0.79), the participation in a disease management program (HR 0.69) and the use of antidiabetics other than insulin (HR 0.74) were generally associated with a reduced risk.
CONCLUSIONS: Only a minority of patients with T2DM and an incident CV comorbidity receive a treatment fully adherent with guideline recommendations. This may contribute to high mortality rates in this population in clinical practice.

BACKGROUND: New recommendations call for lowering LDL-C < 55 mg/dL and non-HDL-C < 85 mg/dL in very-high cardiovascular risk (VH-CVR) patients with type 2 diabetes (T2DM). This study assessed the proportion of VH-CVR diabetics currently meeting these primary and secondary lipid targets, and which therapies/phenotypes predict combined goals achievement.
METHODS: We analysed the cardiometabolic phenotype, use of lipid-modulatind drugs (LMD), pre- and post-LMD lipids levels, and CV complications among 1196 T2DM with high (n = 221; 18%) or VH-CVR (n = 975; 82%). Among the latter, the characteristics of combined lipid goal-achievers (n = 158) were compared to those of non-achievers (n = 817), with subgroup analyses of on-statin patients (n = 732) and those with established CVD taking statins (n = 362). Presence of statin-associated muscle symptoms (SAMS) was also recorded.
RESULTS: 75% of VH-CVR patients were on statins. Both LDL-C and non-HDL-C goals were achieved by 16.2% of all VH-CVR, 19.3% of on-statin VH-CVR, and 24.3% of patients with established CVD taking statins. Achieving both targets was associated with high-intensity statins, specifically rosuvastatin, [statin + ezetimibe] combination, lower baseline LDL-C, smaller LDLs, lower TG and lipoprotein(a), and reduced metabolic syndrome frequency. SAMS reporting did not differ between achievers and non-achievers.
CONCLUSIONS: More than 80% of patients are above targets. To bridge this gap, apart from treating more LMD-naive/refractory diabetics, one should consider for LDL-C to put most patients on high-intensity statins, more often with ezetimibe and, within statins, to switch preferably to rosuvastatin. As regards non-HDL-C, the off-target patients\' phenotype suggests that intensifying lifestyle measures against metabolic syndrome should supplement current therapies.

The epidemic of the century, Diabetes Mellitus (DM) is continuously rising. Intensive research is urgently needed whereby experimental models represent an essential tool to optimise the diagnostic strategy and to improve therapy. In this review, we describe the central principles of the metabolic tests available in order to study glucose and insulin homeostasis in mice, focusing on the most widely used - the glucose and insulin tolerance tests. We provide detailed experimental procedures as well as the practical implementation of these methods and discuss the main factors that should be taken into account when using this methodology.

The recent American Diabetes Association and the European Association for the Study of Diabetes guideline mentioned glycaemia management in type 2 diabetes mellitus (T2DM) patients with cardiovascular diseases (CVDs); however, it did not cover the treatment approaches for patients with T2DM having a high risk of CVD, and treatment and screening approaches for CVDs in patients with concomitant T2DM. This consensus guideline undertakes the data obtained from all the cardiovascular outcome trials (CVOTs) to propose approaches for the T2DM management in presence of CV comorbidities. For patients at high risk of CVD, metformin is the drug of choice to manage the T2DM to achieve a patient specific HbA1c target. In case of established CVD, a combination of glucagon-like peptide-1 receptor agonist with proven CV benefits is recommended along with metformin, while for chronic kidney disease or heart failure, a sodium-glucose transporter proteins-2 inhibitor with proven benefit is advised. This document also summarises various screening and investigational approaches for the major CV events with their accuracy and specificity along with the treatment guidance to assist the healthcare professionals in selecting the best management strategies for every individual. Since lifestyle modification and management plays an important role in maintaining the effectiveness of the pharmacological therapies, authors of this consensus recommendation have also briefed on the patient-centric non-pharmacological management of T2DM and CVD.