Antihyperglycemic drugs have potential therapeutic benefits for inflammatory bowel disease (IBD). We aimed to investigate the association between genetic variations in gene-targeted antihyperglycemic drugs and the risk of IBD.

Summary statistics for HbA1c data were from the UK Biobank including 344,182 participants. Statistics of IBD were obtained from UK Inflammatory Bowel Disease Genetics. Two Mendelian randomization methods were employed to derive the main findings.

In the SMR analysis, increased expression of genetic variations in SGLT2 inhibitor targets (gene: SLC5A2) was linked to a higher risk of CD (OR: 1.97, P = 0.048). Genetic variation in brain cerebellum tissue of sulfonylurea targets (gene: ABCC8) expression was positively associated with IBD (OR = 1.11, P = 0.000). The genetic variation in the GLP-1RA targets (gene: GLP1R) expression was positively correlated with IBD (OR: 1.45, P = 0.039). The IVW-MR analysis suggested reduced IBD and CD risk with expression of increased genetic variation in the thiazolidinediones targets (gene: PPARG).

Genetic variations in SGLT2 inhibitor targets might be associated with an increased risk of CD. The ABCC8 gene might be linked to IBD, CD, and UC. There might be a positive correlation between genetic variation in the GLP-1RA targets expression and IBD occurrence.

In the past 2 decades, health care has witnessed technological and pharmacological advancements leading to innovations in diabetes management. Despite these advances, published guidelines, and treatment algorithms, most people with diabetes remain above glycemic targets. Thus, the authors designed a novel care model aimed at improving several causative factors, including therapeutic inertia, limited access to endocrinology and cardiovascular specialists, time constraints, and complexity in incorporating clinical practice guidelines. The model involves collaboration between the diabetes specialty team and primary care providers (PCPs). The intervention reviewed uncontrolled diabetes data and the patient's electronic medical record (EMR) and sent personalized, evidence-based recommendations to the provider using the task function in the EMR. Other services (eg, diabetes education) were utilized to optimize patient care to achieve optimal glycemic targets and address cardiometabolic risk. The overall mean hemoglobin A1c (HbA1c) decreased pre-post intervention by almost 1%, and 52.1% (347 of 666) of the cohort had ≥-0.5% change in HbA1c post-intervention. All pathways exhibited a decrease in HbA1c. Team-based approaches to managing diabetes patient care were the most effective. The interventions effectively utilized the resources across the health system without placing additional load or burden on primary care or diabetes specialty care teams. In the future, the authors hope to address the limitations of the current gap caused by increasing diabetes numbers, decreasing availability of PCPs and endocrinologists, and fee-for-service models using the innovative specialty consultant-primary care connection and knowledge exchange offered by this novel model, which can only be sustained with payer's support.

The objective of this study was to examine the price sensitivity for provider visits among Medicare Advantage beneficiaries.

We used Medicare Advantage encounter data from 2014 to 2017 accessed as part of an evaluation for the Center for Medicare & Medicaid Innovation.

We analyzed the effect of cost-sharing on the utilization of 2 outcome categories: number of visits (specialist and primary care) and the probability of any visit (specialist and primary care). Our main independent variable was the size of the copayment for the visit, which we regressed on the outcomes with several beneficiary-level and plan-level control variables.

We included beneficiaries with at least 1 of 4 specific chronic conditions and matched comparison beneficiaries. We did not require beneficiaries to be continuously enrolled from 2014 to 2017, but we required a full year of data for each year they were observed. This resulted in 371,140 beneficiary-year observations.

Copay reductions were associated with increases in utilization, although the changes were small, with elasticities <-0.2. We also found evidence of substitution effects between primary care provider (PCP) and specialist visits, particularly cardiology and endocrinology. When PCP copays declined, visits to these specialists also declined.

We find that individuals with chronic conditions respond to changes in copays, although these responses are small. Reductions in PCP copays lead to reduced use of some specialists, suggesting that lowering PCP copays could be an effective way to reduce the use of specialist care, a desirable outcome if specialists are overused.

To compare (in the LIRA-PRIME [NCT02730377], a randomized open-label trial), the efficacy of liraglutide in controlling glycaemia versus an oral antidiabetic drug (OAD) in patients with uncontrolled type 2 diabetes (T2D), despite metformin use in a primary care setting (n = 219 sites, n = 9 countries).

Adults (n = 1991) with T2D (HbA1c 7.5%-9.0%) receiving metformin were randomized 1:1 to liraglutide (≤1.8 mg/d) or one OAD, selected by the investigator, added to metformin, for up to 104 weeks. Primary endpoint: time to inadequate glycaemic control (HbA1c > 7.0%) at two scheduled consecutive visits after week 26. Outcomes were assessed for liraglutide versus a pooled OAD group, and (post hoc) liraglutide versus sodium-glucose co-transporter-2 inhibitors, dipeptidyl peptidase-4 inhibitors, and sulphonylureas individually.

Among randomized patients (liraglutide, n = 996; OAD, n = 995), 47.6% were female, mean age was 57.4 years and mean HbA1c was 8.2%. Median time to inadequate glycaemic control was 44 weeks longer with liraglutide versus OAD (109 weeks [25% percentile, 38; 75% percentile, not available] vs. 65 weeks [25% percentile, 35; 75% percentile, 107], P < .0001). Changes in HbA1c and body weight at week 104 or at premature treatment discontinuation significantly favoured liraglutide over OAD. Hypoglycaemia rates were comparable between groups and few patients discontinued because of adverse events (liraglutide, 7.9% [n = 79]; OAD, 4.1% [n = 41]). Similar results were observed in the post hoc analysis for liraglutide versus individual OAD classes.

Glycaemic control was better maintained with liraglutide versus OAD, supporting liraglutide use when intensifying therapy in primary care patients with T2D.

Swertiamarin is a lead, biologically active compound obtained from Enicostemma littorale Blume and known to be identified for the anti-diabetic activity. Present work comprises the synthesis and structural optimization of seven novel swertiamarin analogues and those were not being reported elsewhere till date. Swertiamarin was isolated, followed by modifications that have been accomplished amidst fluorinating, acetylating and oxidizing agents and also performed chromatographic purity and characterization of analogues. Furthermore, the swertiamarin analogues were screened for dipeptidyl peptidase IV (DPP-IV) enzyme inhibition with in silico studies. Besides, the pharmacokinetics and toxicity of analogues were predicted using ADMET software. In a nutshell, the compounds such as SNIPERSV-4 and SNIPERSV-7 have to pose good initial activity (∼48%) in comparison to standard DPP-IV inhibitor (Sitagliptin). The identified analogues were active against DPP-IV enzyme in preliminary screenings, and these findings would be beneficial for the new age researchers also for the therapy of diabetes.

Preclinical and clinical data of dipeptidyl peptidase 4 (DPP-4) inhibitors have demonstrated discordant data regarding acute kidney injury (AKI). Therefore, we aimed to evaluate the association between DPP-4 use and AKI. This cohort study utilized data from the Department of Veterans Affairs evaluating patients diagnosed with type 2 (T2) diabetes with a DPP-4 inhibitor and compared with nondiabetic and diabetic patients. The primary end point is the development of AKI, and statistical analyses were performed to examine the association. DPP-4 use is associated with a lower odds of AKI compared with diabetics (adjusted odds ratio (OR) = 0.39; 95% confidence interval (CI) = 0.32-0.48) and nondiabetics (OR = 0.64; 95% CI = 0.52-0.79). DPP-4 use in patients with T2 diabetes mellitus is associated with lower odds of AKI within 120 days compared with nondiabetic and diabetic controls when adjusting for study covariates.

Transdifferentiation (TD) is the direct reprogramming of adult cells into cells of alternate fate and function. We have previously shown that liver cells can be transdifferentiated into beta-like, insulin-producing cells through ectopic expression of pancreatic transcription factors (pTFs). However, the efficiency of the process was consistently limited to <15% of the human liver cells treated in culture. The data in the current study suggest that liver-to-pancreas TD is restricted to a specific population of liver cells that is predisposed to undergo reprogramming. We isolated TD-predisposed subpopulation of liver cells from >15 human donors using a lineage tracing system based on the Wnt response element, part of the pericentral-specific promoter of glutamine synthetase. The cells, that were propagated separately, consistently exhibited efficient fate switch and insulin production and secretion in >60% of the cells upon pTF expression. The rest of the cells, which originated from 85% of the culture, resisted TD. Both populations expressed the ectopic pTFs with similar efficiencies, followed by similar repression of hepatic genes. Our data suggest that the TD-predisposed cells originate from a distinct population of liver cells that are enriched for Wnt signaling, which is obligatory for efficient TD. In TD-resistant populations, Wnt induction is insufficient to induce TD. An additional step of chromatin opening enables TD of these cells.

Liver-to-pancreas TD occurs in defined predisposed cells. These cells' predisposition is maintained by Wnt signaling that endows the cells with the plasticity needed to alter their transcriptional program and developmental fate when triggered by ectopic pTFs. These results may have clinical implications by drastically increasing the efficacy of TD in future clinical uses. (Hepatology 2018).

Hemoglobin A1c is an excellent population health measure for the risk of vascular complications in diabetes, while continuous glucose monitoring (CGM) is a tool to help personalize a diabetes treatment plan. The value of CGM in individuals with type 1 diabetes (T1D) has been well demonstrated when compared with utilizing self-monitoring of blood glucose (SMBG) to guide treatment decisions. CGM is a tool for patients and clinicians to visualize the important role that diet, exercise, stress management, and the appropriate selection of diabetes medications can have in managing type 2 diabetes (T2D). Several diabetes organizations have recently reviewed the literature on the appropriate use of CGM in diabetes management and concluded CGM may be a useful educational and management tool particularly for patients on insulin therapy. The indications for using CGM either as a clinic-based loaner distribution model for intermittent use (professional CGM) or a CGM system owned by the patient and used at home with real-time glucose reading (personal CGM) are only beginning to be addressed in T2D. Most summaries of CGM studies conclude that having a standardized glucose pattern report, such as the ambulatory glucose profile (AGP) report, should help facilitate effective shared decision-making sessions. The future of CGM indications for the use of CGM is evolving rapidly. In some instances, CGM is now approved for making medication adjustments without SMBG confirmation and it appears that some forms of CGM will be approved for use in the Medicare population in the United States in the near future. Many individuals with T1D and T2D and their care teams will come to depend on CGM as a key tool for diabetes management.

There is no clear consensus regarding treatment of patients with type 2 diabetes mellitus (T2DM) that is inadequately controlled using dual combination therapy. Recommended agents for triple combination therapy should have complementary mechanisms of action with minimal risk of added side effects such as weight gain and hypoglycemia. We discuss considerations in selecting triple oral therapy regimens in patients with T2DM, and review clinical trial data regarding triple oral therapy using dipeptidyl peptidase-4 (DPP-4) inhibitors.

A search of the PubMed database was conducted to identify clinical trials of triple oral therapy incorporating a DPP-4 inhibitor (November 2013 to January 2015), using the following search terms: 'type 2 diabetes' AND 'alogliptin OR linagliptin OR saxagliptin OR sitagliptin OR vildagliptin' AND 'metformin'. Trials had to include adult patients with T2DM who received triple oral therapy with a DPP-4 inhibitor for ≥18 weeks. The bibliographies of retrieved articles were also searched to identify any other relevant trials.

A total of 17 clinical trials evaluating metformin and a DPP-4 inhibitor combined with a sulfonylurea (SU), thiazolidinedione (TZD), or sodium-glucose cotransporter 2 (SGLT2) inhibitor were identified and included in this review. Consistently, the addition of a DPP-4 inhibitor to metformin and SU, TZD, or SGLT2 inhibitor therapy improved glycemic measures, and these combinations were generally well tolerated. An increased incidence of hypoglycemia was reported for combinations that included an SU.

Triple oral therapy that includes a DPP-4 inhibitor is a valid option for patients with T2DM not adequately controlled with dual combination therapy, and offers an alternative to insulin therapy. Triple oral therapy with a DPP-4 inhibitor, metformin, and a TZD or SGLT2 inhibitor should be considered when avoidance of hypoglycemia is a primary goal.

Clinicians and patients are rapidly adapting GLP-1 receptor agonists as efficacious and safe therapeutic options for managing type 2 diabetes (T2DM). GLP-1 receptor agonists stimulate insulin production and secretion from the pancreatic β cells in a glucose-dependent manner, improve gastric emptying, favor weight reduction, and reduce postabsorptive glucagon secretion from pancreatic α cells. GLP-1 receptor activity is impaired in patients with T2DM. GLP-1 secretion and subsequent physiologic actions in patients with type 1 diabetes (T1DM) is ill-defined. Some researchers have suggested that the use of GLP-1 receptor agonists in T1DM may reduce excessive postprandial glucagon secretion allowing patients to reduce their total daily dose of exogenous insulin. Hypoglycemia risk may also be minimized in T1DM as glucagon counter-regulation can be preserved to some degree via the glucose-dependent action of the GLP-1 receptor agonists. This paper will consider the physiologic and pharmacologic benefits of adding GLP-1 receptor agonists to therapeutic regimens of patients with T1DM.

This study was performed to assess the effect of chronic low-dose sitagliptin, a dipeptidyl peptidase 4 inhibitor, on metabolic profile and on renal lesions aggravation in a rat model of type-2 diabetic nephropathy, the Zucker diabetic fatty (ZDF) rat. Diabetic and obese ZDF (fa/fa) rats and their controls ZDF (+/+) were treated for 6 weeks with vehicle (control) or sitagliptin (10 mg/kg/bw). Blood/serum glucose, HbA1c, insulin, Total-c, TGs, urea, and creatinine were assessed, as well as kidney glomerular and tubulointerstitial lesions (interstitial fibrosis/tubular atrophy), using a semiquantitative rating from 0 (absent/normal) to 3 (severe and extensive damage). Vascular lesions were scored from 0-2. Sitagliptin in the diabetic rats promoted an amelioration of glycemia, HbA1c, Total-c, and TGs, accompanied by a partial prevention of insulinopenia. Furthermore, together with urea increment prevention, renal lesions were ameliorated in the diabetic rats, including glomerular, tubulointerstitial, and vascular lesions, accompanied by reduced lipid peroxidation. In conclusion, chronic low-dose sitagliptin treatment was able to ameliorate diabetic nephropathy, which might represent a key step forward in the management of T2DM and this serious complication.

Glucagon-like peptide-1 (GLP-1) has been the focus of considerable research activity in the treatment of type 2 diabetes mellitus (T2DM) because the incretin effect is significantly reduced or absent in individuals with T2DM. Thus, pharmacologic efforts to develop medications that mimic the actions of GLP-1 have become a target for improving or reversing chronic hyperglycemia. Two GLP-1 receptor agonists are commercially available: exenatide twice daily (b.i.d.) and liraglutide once daily (q.d.). Targeted and individualized intensification of diabetes management can best be accomplished with a thorough understanding of these new medications.

Information was gathered through a search of MEDLINE and PubMed for GLP-1 and glycemic management in patients with type 2 diabetes.

Activation of the GLP-1 receptors on the β-cells results in enhanced levels of insulin biosynthesis, β-cell proliferation, resistance to β-cell apoptosis, and enhanced β-cell survival in both humans and rodents; yet, the risk of hypoglycemia is minimized because insulin production and exocytosis occurs in a glucose-dependent manner. The efficacy and safety of the two commercially available GLP-1 receptor agonists, liraglutide and exenatide, in managing postprandial glycemia have been well documented in numerous clinical trials, in which reductions in glycosylated hemoglobin (HbA1c) levels of -0.79% to -1.12% have been demonstrated. Weight reduction/maintenance and improvements in blood pressure and lipidemia have also been reported.

Because GLP-1 receptor agonists work in a glucose-dependent manner, they are likely to reduce hyperglycemia safely, without a marked fluctuation toward hypoglycemia. In the process of acutely restoring β-cell function, GLP-1 agonists may allow patients to achieve HbA(1c) <7% without experiencing weight gain or hypoglycemia. The ability of GLP-1 receptor agonists to improve blood pressure and postprandial lipidemia in the context of weight neutrality or weight loss may have the potential to ameliorate some of the cardiovascular risks observed in patients with T2DM.