Changes in diabetes prescription patterns following Affordable Care Act Medicaid expansion

IntroductionMost patients with diabetes mellitus are prescribed medications to control their blood glucose. The implementation of the Affordable Care Act (ACA) led to improved access to healthcare for patients with diabetes. However, impact of the ACA on prescribing trends by diabetes drug category is less clear. This study aims to assess if long-acting insulin and novel agents were prescribed more frequently following the ACA in states that expanded Medicaid compared with non-expansion states.Research design and methodsIn this analysis of a natural experiment, prescriptions reimbursed by Medicaid (US public insurance) for long-acting insulins, metformin, and novel agent medications (DPP4 inhibitors, sodium/glucose cotransporter 2 inhibitor antagonists, and glucagon-like peptide-1 receptor agonists) from 2012 to 2017 were obtained from public records. For each medication category, we performed difference-in-differences (DID) analysis modeling change in rate level from pre-ACA to post-ACA in Medicaid expansion states relative to Medicaid non-expansion states.ResultsExpansion and non-expansion states saw a decline in both metformin and long-acting insulin prescriptions per 100 enrollees from pre-ACA to post-ACA. These decreases were larger in non-expansion states relative to expansion states (metformin: absolute DID = +0.33, 95% CI=0.323 to 0.344) and long-acting insulin (absolute DID: +0.11; 95% CI=0.098 to 0.113). Novel agent prescriptions in expansion states (+0.08 per 100 enrollees) saw a higher absolute increase per 100 Medicaid enrollees than in non-expansion states (absolute DID= +0.08, 95% CI=0.079 to 0.086).ConclusionsThere was a greater absolute increase for prescriptions of novel agents in expansion states relative to non-expansion states after accounting for number of enrollees. Reducing administrative barriers and improving the ability of providers to prescribe such newer therapies will be critical for caring for patients with diabetes—particularly in Medicaid non-expansion states.

Changes in the use of diabetes drugs among community-dwelling people with Alzheimer’s disease

Background Type 2 diabetes is common in persons with Alzheimer’s disease (AD). Management of diabetes in persons with AD is challenging due to changing goals of care and susceptibility to adverse drug events including hypoglycemia. The aim of this study was to investigate the prevalence of diabetes drug use from 5 years before to 5 years after the time of AD diagnosis among persons with and without AD. Methods This was a nationwide register-based study of persons with and without AD and diabetes in Finland. We analyzed data from the Medication Use and Alzheimer’s disease (MEDALZ) study that included 70,718 community-dwelling people diagnosed with AD from 2005 to 2011. The study population included 8418 persons with AD and 6666 matched persons without AD who were diagnosed with diabetes 5 years before AD diagnosis (index date). We defined the prevalence of diabetes drug use in three-month evaluation periods from 5 years before until 5 years after the index date. Results Nearly all people with diabetes (94% in both cohorts) used one or more diabetes drugs on the index date. The most prevalent drug metformin was used by 60.9% of people with AD and 59.1% of people without AD. The next most prevalent drugs were sulfonylureas and insulin. The prevalence of diabetes drug use was similar in people with and without AD but began to decline 1 year after AD diagnosis in the AD cohort compared to non-AD cohort. Conclusions The decline in diabetes drug use after AD diagnosis may be attributed to clinicians and patients seeking to avoid serious adverse drug events including hypoglycemia. In addition, the findings may reflect personalized glycemic control and unintentional weight loss in persons with AD reducing the need for diabetes drugs.

Association Between the Diabetes Drug Cost and Cardiovascular Events for Type 2 Diabetes in Korea: A National Health Insurance Service Database Analysis

Background: We aimed to investigate the long-term effects of diabetes drug costs on cardiovascular (CV) events and death. Methods: This retrospective observational study used the 2009–2018 National Health Insurance data in Korea. Among patients with type 2 diabetes, those who were taking antidiabetic drugs and did not have CV events before 2009 were included. Data on the annual cost of each diabetes drug were collected. The 10-year incidence of CV events (cardiac death, non-fatal myocardial infarction, stroke, hospitalization for heart failure, and coronary revascularization) and CV death were analyzed according to the diabetes drug cost quartiles (Q1 [the lowest] – Q4 [the highest]).Results: A total of 441,914 participants were enrolled (median age, 60 years; male, 57%). CV events and death occurred in 28.1% and 8.36% of patients, respectively. The overall diabetes drug cost was USD 271/year per person (range: 1–18,921). The 10-year incidence of CV events and death was lowest in Q3 and high in Q4 and Q1. After adjusting for CV risk factors, the risk of CV events increased in the sequential order of cost quartiles (hazard ratio (HR)=1 [ref], 1.102 [95% confidence interval (CI): 1.084–1.120], 1.137 [95% CI: 1.118–1.156], and 1.323 [95% CI: 1.3011.346]). The risk of CV death showed U-shaped pattern which was lowest in the Q3 (HR=0.943, 95% CI 0.903-0.984) and highest in the Q4 (HR= 1.234, 95% CI 1.182-1.287).Conclusion: The expenditure for diabetes drug affects 10-year CV events and death. Affording an appropriate diabetes cost at a similar CV risk is an independent protective factor for CV death.Trial registration: retrospectively registered

Cardiovascular outcomes after initiating GLP-1 receptor agonist or basal insulin for the routine treatment of type 2 diabetes: a region-wide retrospective study

Aim We aimed to compare cardiovascular outcomes of patients with type 2 diabetes (T2D) who initiated GLP-1 receptor agonists (GLP-1RA) or basal insulin (BI) under routine care. Methods We accessed the administrative claims database of the Veneto Region (Italy) to identify new users of GLP-1RA or BI in 2014–2018. Propensity score matching (PSM) was implemented to obtain two cohorts of patients with superimposable characteristics. The primary endpoint was the 3-point major adverse cardiovascular events (3P-MACE). Secondary endpoints included 3P-MACE components, hospitalization for heart failure, revascularizations, and adverse events. Results From a background population of 5,242,201 citizens, 330,193 were identified as having diabetes. PSM produced two very well matched cohorts of 4063 patients each, who initiated GLP-1RA or BI after an average of 2.5 other diabetes drug classes. Patients were 63-year-old and only 15% had a baseline history of cardiovascular disease. During a median follow-up of 24 months in the intention-to-treat analysis, 3P-MACE occurred less frequently in the GLP-1RA cohort (HR versus BI 0.59; 95% CI 0.50–0.71; p < 0.001). All secondary cardiovascular endpoints were also significantly in favor of GLP-1RA. Results were confirmed in the as-treated approach and in several stratified analyses. According to the E-value, confounding by unmeasured variables were unlikely to entirely explain between-group differences in cardiovascular outcomes. Conclusions Patients with T2D who initiated a GLP-1RA experienced far better cardiovascular outcomes than did matched patients who initiated a BI in the same healthcare system. These finding supports prioritization of GLP-1RA as the first injectable regimen for the management of T2D.

Pioglitazone administration restores a PPARG-dependent transcriptional network and ATP levels within skeletal muscles of mice implanted with patient-derived breast tumors

BackgroundFatigue is common in patents with breast cancer (BC), and can occur in patients with early stage disease and in the absence of muscle wasting (i.e. cachexia). We have reported transcriptional and proteomic alterations in muscles from BC patients, which are associated with fatigue. Mice implanted with human BC xenografts recapitulate the muscle molecular composition changes seen in patients, coupled with a greater rate of contraction-induced fatigue. Multiple bioinformatics platforms in both human and mouse muscles have identified peroxisome proliferator activated receptor gamma (PPARG) as central to this phenotype, with multiple PPARG target genes downregulated in response to tumor growth. The current study tested the hypothesis that the PPARG agonist pioglitazone (pio), a commonly prescribed diabetes drug, would rescue the transcriptional alterations observed in muscles of tumor-bearing mice.MethodsSixteen female NSG mice were implanted with breast cancer patient-derived orthotopic xenografts (BC-PDOX) via transplantation of Her2/neu+ human tumor fragments. BC-PDOX mice were randomly assigned to a treatment group that received daily oral pio at 30 mg.kg-1 (n=8), or a control group that received a similar volume of vehicle (n=8). Treatment was initiated when tumors reached a volume of 600mm3, and lasted for 2-weeks. Hindlimb muscles were isolated from BC-PDOX and non-tumor bearing mice for RNA-sequencing, gene expression validation, and ATP quantification. Differentially expressed genes (DEGs) in muscles from BC-PDOX mice relative to non-tumor bearing controls were identified using DESeq2, and multiple bioinformatics platforms were employed to contextualize the DEGs.ResultsWe found that the administration of pio restored the muscle gene expression patterns of BC-PDOX mice to a profile resembling muscles of non-tumor bearing NSG control mice. Validation of skeletal muscle gene expression by qPCR confirmed pio increased the expression of PPARG target genes in skeletal muscles. Isolated mitochondria from muscles of BC-PDOX mice treated with pio contained greater levels of ATP. There were no differences in body weights, muscle weights, or tumor volumes in pio vs. vehicle treated BC-PDOX mice.ConclusionsThese data demonstrate that oral pio supplementation rescues the BC-associated downregulation of PPARG target genes in skeletal muscle. Additionally, muscles from BC-PDOX mice treated with pio had greater levels of ATP, which would be associated a more fatigue-resistant muscle phenotype. Therefore, we propose that the FDA-approved and generic diabetes drug, pio, be considered as a supportive therapy for the treatment of BC-associated muscle fatigue.

Potential of Bioactive Compounds of Arenga Vinegar as Traditional Medicine Through Reverse Docking Techniques

Background: Arenga vinegar (Arenga pinnata) has been trusted by the indigenous people of Kampung Kuta as traditional medicine, one of which is used as a diabetes medicine. For this reason, the aim of this study is to examine the bioactive compounds contained in arenga vinegar, namely acetic acid, which is predicted to be scientifically proven using reverse docking techniques. Methods: This research is descriptive qualitative research, by interpreting the data obtained from databases and software. Results: There is a binding pose between acetic acid and the sucrase-isomaltase enzyme, the lowest binding affinity value is -3.2 kcal/mol, and the binding site occurs hydrophobic interactions with the amino acids Trp327 (A), Asp355 (A), Ile392 (A), Trp470 (A), Phe604 (A), His629 (A), Trp586 (A) as well as hydrogen bonding to the amino acid Asp(472)A. Conclusions: The acetic acid-binding pose binds well to the sucrase-isomaltase enzyme so that the binding affinity value appears even though the value is not too low and the binding site occurs, this can be used as proof of the belief of the indigenous people of Kampung Kuta, namely the treatment of arenga vinegar as a diabetes drug, especially as a level control blood sugar.

Canagliflozin Increases Intestinal Adenoma Burden in Female ApcMin/+ Mice

The diabetes drug canagliflozin extends life span in male mice. Since malignant neoplasms are the major cause of death in most mouse strains, this observation suggests that canagliflozin might exert anti-neoplastic effects in male mice. Here, we treated a mouse neoplasia model, the adenoma-prone ApcMin/+ strain, with canagliflozin, to test the effects of this drug on intestinal tumor burden. Surprisingly, canagliflozin increased the total area of intestine involved by adenomas, an effect most marked in the distal intestine and in female mice. Immunohistochemical analysis suggested that canagliflozin may not influence adenoma growth via direct SGLT1/2 inhibition in neoplastic cells. Our results are most consistent with a model where canagliflozin aggravates adenoma development by altering the anatomic distribution of intestinal glucose absorption, as evidenced by increases in postprandial GLP-1 levels driven by delayed glucose absorption. We hypothesize that canagliflozin exacerbates adenomatosis in the ApcMin/+ model via complex, cell-non-autonomous mechanisms, and that sex differences in GLP-1 responses may in part underlie sexually dimorphic effects of this drug on life span.