Extrahepatic malignancies are the leading cause of death in patients with nonalcoholic fatty liver disease (NAFLD). Of these cancers, pancreatic cancer is one of the most lethal; however, the link between NAFLD and pancreatic cancer remains unclear. Recently, various research results have been reported on the association between NAFLD and pancreatic cancer, and the results of compiling this information revealed the following. First, the prevalence of pancreatic cancer in patients with NAFLD is at 0.26%. Second, the currently evident pathogenesis includes intrapancreatic risk factors, such as: (1) non-alcoholic fatty pancreas disease, and (2) intraductal papillary mucinous neoplasm; and extrapancreatic risk factors, such as: (1) insulin resistance and adipocytokines, (2) proinflammatory cytokines, and (3) dysbiosis. Finally, metformin and sodium-glucose cotransporter 2 inhibitors may reduce the risk of pancreatic cancer in diabetes patients with NAFLD. In this review, we summarize the recent evidence on the epidemiology and mechanisms for NAFLD-related pancreatic cancer. We further discuss the impact of anti-diabetic medication on pancreatic cancer.

Background: Prevalence of type 2 diabetes (T2D) is rising, and its burden on the healthcare system remains a challenge. Consumption of a plant-predominant diet is a promising approach for achieving remission, which has emerged as a therapeutic target. Objective: To establish feasibility of achieving T2D remission with a plant-predominant diet in a cohort of free-living individuals. Methods: Patients referred to a wellness clinic were treated with a low-fat, whole food, plant-predominant diet while receiving standard medical treatment. Included patients were adults, mostly elderly, with HbA1c > 6.5%, with or without use of antidiabetic medications. Results: N = 59 patients were included in this analysis, with mean age 71.5 years (range 41-89). Twenty-two (37%) patients achieved T2D remission. Mean differences showed a significant decrease post-lifestyle change (T2) compared to prior to lifestyle change (T1) for the following outcomes [least squares mean difference (95% CI)]: BMI [-2.6 (-4.8, -.3)] kg/m2; HbA1c [ -1.3 (-1.6, -1.0)] %; and fasting glucose [-29.6 (-41.8, -17.5)] mg/dL. No significant differences were observed for systolic or diastolic blood pressure, HDL, LDL, or triglycerides. Conclusion: A lifestyle-based treatment intervention promoting adherence to a plant-predominant diet and integrated as part of routine care can successfully achieve T2D remission in wellness clinic patients.

Diabetic retinopathy (DR) is the most frequent complication of type 2 diabetes and remains the leading cause of preventable blindness. Current clinical decisions regarding the administration of antidiabetic drugs do not sufficiently incorporate the risk of DR due to the inconclusive evidence from preceding meta-analyses. This umbrella review aimed to systematically evaluate the effects of antidiabetic drugs on DR in people with type 2 diabetes.
A systematic literature search was undertaken in Medline, Embase, and the Cochrane Library (from inception till 17th May 2022) without language restrictions to identify systematic reviews and meta-analyses of randomized controlled trials or longitudinal studies that examined the association between antidiabetic drugs and DR in people with type 2 diabetes. Two authors independently extracted data and assessed the quality of included studies using the AMSTAR-2 (A MeaSurement Tool to Assess Systematic Reviews) checklist, and evidence assessment was performed using the GRADE (Grading of recommendations, Assessment, Development and Evaluation). Random-effects models were applied to calculate relative risk (RR) or odds ratios (OR) with 95% confidence intervals (CI). This study was registered with PROSPERO (CRD42022332052).
With trial evidence from 11 systematic reviews and meta-analyses, we found that the use of glucagon-like peptide-1 receptor agonists (GLP-1 RA), sodium-glucose cotransporter-2 inhibitors (SGLT-2i), or dipeptidyl peptidase-4 inhibitors (DPP-4i) was not statistically associated with the risk of DR, compared to either placebo (RR: GLP-1 RA, 0.98, 0.89-1.08; SGLT-2i, 1.00, 95% CI 0.79-1.27; DPP-4i, 1.17, 0.99-1.39) or other antidiabetic drugs. Compared to other antidiabetic drugs, meglitinides (0.34, 0.01-8.25), SGLT-2i (0.73, 0.10-5.16), thiazolidinediones (0.92, 0.67-1.26), metformin (1.15, 0.81-1.63), sulphonylureas (1.24, 0.93-1.65), and acarbose (4.21, 0.44-40.43) were not statistically associated with the risk of DR. With evidence from longitudinal studies only, insulin was found to have a higher risk of DR than other antidiabetic drugs (OR: 2.47, 95% CI: 2.04-2.99).
Our results indicate that antidiabetic drugs are generally safe to prescribe regarding the risk of DR among people with type 2 diabetes. Further robust and large-scale trials investigating the effects of insulin, meglitinides, and acarbose on DR are warranted.
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=332052, identifier CRD42022332052.

The fight against aging is an eternal pursuit of humankind. The aging rate of patients with type 2 diabetes mellitus (T2DM) is higher than that of healthy individuals. Reducing the aging rate of patients with T2DM and extending their life expectancy are challenges that endocrinologists are eager to overcome. Many studies have shown that antidiabetic medications have potent anti-aging potential. Telomeres are repetitive DNA sequences located at the ends of chromosomes, and telomere shortening is a hallmark of aging. This review summarizes clinical trials that have explored the association between antidiabetic medications and telomere length (TL) in patients with T2DM and explore the mystery of delaying aging in patients with T2DM from the perspective of telomeres. Various antidiabetic medications may have different effects on TL in patients with T2DM. Metformin and sitagliptin may protect telomeres in patients with T2DM, while exogenous insulin may promote telomere shortening in patients with T2DM. The effect of acarbose and glyburide on TL in patients with T2DM is still uncertain due to the absence of evidence from longitudinal studies.

UNASSIGNED: The aim of this study was to evaluate the factors affecting adherence to antidiabetic medication among diabetic patients in India.
UNASSIGNED: A qualitative study was conducted among 40 diabetic patients aged >30 years, on treatment for more than a year without any complications in the Urban Health Centre of Dayanand Medical College and Hospital, Ludhiana, Punjab, India.
UNASSIGNED: A semistructured questionnaire was harnessed to congregate data by interviewing the patients for 30-40 min in person. The interviews were recorded in the form of audios by acquiring informed consent and transcribed verbatim. The factors were then divided into barriers and enablers which were further subdivided into themes and subthemes as a result of which four major themes were built including individual, social, organizational, and community levels. These major themes were further categorized into several subthemes to assess the nonadherence to antidiabetic medications.
UNASSIGNED: The results of the interviews depicted that the lack of knowledge, financial problems, familial issues, misconceptions regarding the disease, and side effects of taking medications daily were the major altruist for nonadherence, whereas on the other hand, positive perception about the disease, family support, and getting medications on affordable prices by some health-care institutes played an important role in enabling medication adherence as about 50% patients were adherent to the medications. Moreover, various interventions were used to escort the patients regarding medication compliance and blood glucose level monitoring such as lifestyle modifications (diet and exercise), use of reminders for medication intake on time, encouraging them to visit health-care centers, or hospitals on time for regular check-ups and by educating them regarding the long-term effects of diabetes and its prevention.

UNASSIGNED: Medication adherence is an integral component in the management of patients with co-morbid type 2 diabetes mellitus (T2DM) and hypertension. However due to their combined conditions, there is likelihood of polypharmacy and medication-related burden, which could negatively impact adherence to therapy. This study aimed to assess the perceived medication-related burden among patients with co-morbid T2DM and hypertension and to evaluate the association between the perceived burden and adherence to medication therapy.
UNASSIGNED: A cross-sectional study was conducted among adult patients with co-morbid T2DM and hypertension attending a primary health facility. The living with medicines questionnaire and the medication adherence report scale were used to assess extent of medication-related burden and adherence respectively. Binary logistic regression model was used to estimate the adjusted odds and their corresponding 95% confidence interval for medication-related burden and adherence outcomes. All observed categorical variables were considered for the multivariable binary logistic regression model.
UNASSIGNED: The total number of participants was 329 with a median age of 57.5 ± 13.2 years. The median score for the overall burden was 99 (IQR: 93-113), and this significantly varied by sex (p = 0.012), monthly income (p = 0.025), monthly expenditure on medications (p = 0.012), frequency of daily dose of medications (p = 0.020) and family history of T2DM (p < 0.001). About 30.7% and 36.8% of participants reported moderate/high burden and medication adherence respectively. Uncontrolled diastolic blood pressure (AOR: 2.46, 95% CI: 1.20-5.05, p = 0.014), high glucose (AOR: 4.24, 95% CI: 2.13-8.46, p < 0.001) and no family history of T2DM (AOR: 2.14, 95% CI: 1.14-4.02, p = 0.026) were associated with moderate/high medication burden. Uncontrolled diastolic blood pressure (AOR: 0.48, 95% CI: 0.25-0.94, p = 0.031), at least 5 years since hypertension diagnosis (AOR: 0.55, 95% CI: 0.30-0.99, p = 0.045) and moderate/high medication-related burden (AOR: 0.33, 95% CI: 0.16-0.69, p = 0.003) were associated with lower odds of medication adherence.
UNASSIGNED: These findings suggest that to improve the preventive and optimal care of patients with T2DM and hypertension, interventions that aim to reduce medication-related burden and morbidity are recommended. The study proposes that health stakeholders such as clinicians, pharmacists, and policy makers, develop multidisciplinary clinical and pharmaceutical care interventions to include provision of counselling to patients on adherence. In addition, developing policies and sensitization activities on deprescribing and fixed-dose drug combinations aimed at reducing medication-related burden, while promoting better adherence, blood pressure and blood glucose outcomes are recommended.

The global prevalence of obesity is increasing rapidly with an exponential rise in incidence of type 2 diabetes mellitus in recent years. \'Diabesity\', the term coined to show the strong interlink between obesity and diabetes, is the direct cons-equence of the obesity pandemic, and poses significant challenges in the management of the disease. Without addressing the clinical and mechanistic complications of obesity such as metabolic-associated fatty liver disease and obstructive sleep apnoea, a rational management algorithm for diabesity cannot be developed. Several classes of anti-diabetic medications including insulins, sulphonylureas, thiazolidinediones and meglitinides are associated with the risk of weight gain and may potentially worsen diabesity. Therefore, appropriate selection of antidiabetic drug regimen is crucial in the medical management of diabesity. The role of non-pharmacological measures such as dietary adjustments, exercise interventions and bariatric procedures should also be emphasised. Unfortunately, the importance of appropriate and optimal management of diabesity is often overlooked by medical professionals when achieving adequate glycemic control which results in inappropriate management of the disease and its complications. This review provides a narrative clinical update on the evidence behind the management of diabesity.

Several epidemiological studies have clearly identified diabetes mellitus (DM) as a major risk factor for cognitive dysfunction, and it is going to be a major public health issue in the coming years because of the alarming rise in diabetes prevalence across the world. Brain and neural tissues predominantly depend on glucose as energy substrate and hence, any alterations in carbohydrate meta-bolism can directly impact on cerebral functional output including cognition, executive capacity, and memory. DM affects neuronal function and mental capacity in several ways, some of which include hypoperfusion of the brain tissues from cerebrovascular disease, diabetes-related alterations of glucose transporters causing abnormalities in neuronal glucose uptake and metabolism, local hyper- and hypometabolism of brain areas from insulin resistance, and recurrent hypoglycemic episodes inherent to pharmacotherapy of diabetes resulting in neuronal damage. Cognitive decline can further worsen diabetes care as DM is a disease largely self-managed by patients. Therefore, it is crucial to understand the pathobiology of cognitive dysfunction in relation to DM and its management for optimal long-term care plan for patients. A thorough appraisal of normal metabolic characteristics of the brain, how alterations in neural metabolism affects cognition, the diagnostic algorithm for patients with diabetes and dementia, and the management and prognosis of patients when they have this dangerous combination of illnesses is imperative in this context. This evidence-based narrative with the back-up of latest clinical trial reviews elaborates the current understanding on diabetes and cognitive function to empower physicians to manage their patients in day-to-day clinical practice.

Epidemiologic evidence is limited about associations between T2DM, metformin, and the risk of non-Hodgkin\'s lymphoma (NHL). We aimed to examine associations between T2DM, metformin, and the risk of NHL in the Women\'s Health Initiative (WHI) Study. Information on T2DM status (diabetes status/types of antidiabetic drug use/diabetes duration) from study enrollment and during follow-up were assessed. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to evaluate associations of T2DM status with risks of overall NHL and its three major subtypes [diffuse large B-cell lymphoma (DLBCL, n = 476), follicular lymphoma (FL, n = 301) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL, n = 136)] based on multivariable-adjusted Cox proportional hazards models. During a median follow-up of 18.86 years (range, 0.01-25.13; SD ± 6.55), a total of 1637 women developed NHL among 147 885 postmenopausal women. Women with T2DM and with self-reported oral medication use had 38% and 55% higher risk of DLBCL, respectively [multivariable-adjusted model HR = 1.38, 95% CI (1.06-1.81) and HR = 1.55, 95% CI (1.16-2.06)] compared to the reference group (nondiabetics/untreated diabetes). Risks of NHL and DLBCL [multivariable-adjusted model: HR = 1.28, 95% CI (1.06-1.54) and HR = 1.56, 95% CI (1.13-2.14), respectively] were significantly higher in associations with relatively short duration (≤7 years) of diabetes, compared to reference group. Additionally, an increased risk of DLBCL [HR = 1.76, 95% CI (1.13-2.75)] was found in metformin users compared to the reference group. Postmenopausal women who had T2DM, who were oral antidiabetic drug users, especially metformin, and who had a shorter diabetes duration may have higher risks of DLBCL. Further well-designed research is needed to confirm our findings.

Over the past century, since the discovery of insulin, the therapeutic offer for diabetes has grown exponentially, in particular for type 2 diabetes (T2D). However, the drugs in the diabetes pipeline are even more promising because of their impressive antihyperglycemic effects coupled with remarkable weight loss. An ideal medication for T2D should target not only hyperglycemia but also insulin resistance and obesity. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and the new class of GLP1 and gastric inhibitory polypeptide dual RAs counteract 2 of these metabolic defects of T2D, hyperglycemia and obesity, with stunning results that are similar to the effects of metabolic surgery. An important role of antidiabetic medications is to reduce the risk and improve the outcome of cardiovascular diseases, including coronary artery disease and heart failure with reduced or preserved ejection fraction, as well as diabetic nephropathy, as shown by SGLT2 inhibitors. This review summarizes the main drugs currently under development for the treatment of type 1 diabetes and T2D, highlighting their strengths and side effects.