Diabetes Mellitus Wetenschap

Cost-Utility Analysis of Dapagliflozin Versus Saxagliptin Treatment as Monotherapy or Combination Therapy as Add-on to Metformin for Treating Type 2 Diabetes Mellitus.

Appl Health Econ Health Policy. 2020 Aug 12;:

Authors: Hu S, Deng X, Ma Y, Li Z, Wang Y, Wang Y

Abstract
OBJECTIVE: To assess the long-term cost effectiveness of dapagliflozin (DAPA) and saxagliptin (SAXA) separately or together in patients with type 2 diabetes mellitus (T2DM) inadequately controlled by metformin (MET).
METHODS: Five head-to-head randomised controlled trials of the efficacy of DAPA and SAXA in type 2 diabetes mellitus (T2DM) patients were found by searching PubMed, Embase and Cochrane from inception to October 2019. The lifetime disease progression and long-term effectiveness of therapy in patients were projected by the United Kingdom Prospective Diabetes Study Outcome Model 2 (UKPDS OM2) in three T2DM therapeutic groups: DAPA + SAXA, DAPA and SAXA. Each group used DAPA and/or SAXA as an add-on therapy to MET. The study took the perspective of Chinese healthcare service providers. Univariate, scenario and probabilistic sensitivity analyses were performed.
RESULTS: The quality-adjusted life-years (QALYs) value of the DAPA + SAXA, SAXA and DAPA groups were 11.28, 11.26 and 11.45 years, respectively. The total costs were US$27,954.84, US$23,254.46 and US$25,608.49, respectively. DAPA was dominant over DAPA + SAXA. The DAPA + SAXA group presented an estimated QALY gain of 0.02 and a total cost increase of US$4700.39 over the SAXA group, with an incremental cost of US$217,530.10 per QALY. Compared with the SAXA group, the DAPA group had a QALY gain of 0.19 years and a total cost increase of US$2354.04, for an incremental cost of US$12,191.97 per QALY. The pharmacoeconomic results were robust to univariate, scenario and probabilistic sensitivity analyses.
CONCLUSIONS: Compared with DAPA + SAXA or SAXA, DAPA appears to be a cost-effective therapy as add-on to MET for Chinese patients whose T2DM is insufficiently controlled by MET.

PMID: 32783086 [PubMed - as supplied by publisher]

An Observational Study of Reduction in Glycemic Parameters and Liver Stiffness by Saroglitazar 4 mg in Patients With Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease.

Cureus. 2020 Jul 08;12(7):e9065

Authors: Mitra A

Abstract
Background Metabolic abnormal conditions, such as diabetes and high triglycerides (TGs), are commonly associated with nonalcoholic fatty liver disease (NAFLD). Currently, there is no approved pharmacotherapy for NAFLD. Saroglitazar, the world's first approved dual peroxisome proliferator-activated receptors (PPAR) α and γ agonist, was approved in India for the treatment of diabetic dyslipidemia. The objective of this study was to observe the safety and effectiveness of saroglitazar, 4 mg once daily, in reducing glycemic parameters and liver fibrosis in type 2 diabetes mellitus (T2DM) patients with NAFLD.  Method In this prospective observational study, we enrolled 30 patients with T2DM and NAFLD (primarily detected by ultrasonography (USG) of the abdomen) who were treated with saroglitazar, 4 mg once daily, and the follow-up data were available for six months after saroglitazar treatment. During follow up, all patients were on stable antidiabetic and statin therapy. Liver stiffness was measured by FibroScan® (Echosens™ North America, Waltham, MA) elastography at baseline and at the six-month follow-up. Results At the six-month follow-up after saroglitazar treatment, significant improvement was observed in glycemic parameters, liver stiffness on FibroScan, and serum transaminase levels. The serum TG levels were significantly reduced with saroglitazar. No major adverse event was reported. Conclusion In this observational study of patients with T2DM and NAFLD, saroglitazar improved liver stiffness, as well as the glycemic and lipid parameters. A long-term randomized controlled clinical trial is required to further establish the safety and efficacy of saroglitazar in the treatment of T2DM and NAFLD.

PMID: 32782883 [PubMed]

Lower serum 25-hydroxyvitamin D levels are associated with impaired glomerular filtration rate in type 2 diabetes patients.

Ther Adv Endocrinol Metab. 2020;11:2042018820930904

Authors: Dall'Agnol A, Brondani LA, Cancelier VDA, Camargo EG, Silveiro SP

Abstract
Background: 25-Hydroxyvitamin D [25(OH)D] deficiency has been implicated as a possible risk factor for the onset and progression of diabetes kidney disease (DKD). The aim of this study was to evaluate the interaction between levels of 25(OH)D and DKD in type 2 diabetes mellitus (DM) patients.
Methods: Cross-sectional design, outpatient type 2 DM. Glomerular filtration rate (GFR) was measured by 51Cr-EDTA and estimated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), urinary albumin excretion (UAE) by immunoturbidimetry, and 25(OH)D by chemiluminescence. Receiver operating characteristic (ROC) curve analysis and generalized linear model (Poisson robust regression estimator) were used to assess the interaction between 25(OH)D levels and renal function.
Results: A total of 114 type 2 DM patients aged 60 ± 10 years, 49 males (43%), DM duration 22 ± 10 years, with GFR > 60 ml/min/1.73 m2 were evaluated. Patients with GFRs 60-90 (n = 50) had significantly lower 25(OH)D levels than individuals with GFRs > 90 ml/min/1.73 m2 (n = 64), respectively 40 ± 20 versus 48 ± 20 nmol/l, p = 0.027. This difference was more pronounced for older individuals (39 ± 20 versus 54 ± 23 nmol/l, respectively), and Poisson robust regression disclosed that lower 25(OH)D [Poisson regression (PR) = 0.989, confidence interval (CI): 0.978-0.999, p = 0.034], and advanced age (PR = 1.050, CI: 1.007-1.096, p = 0.023) were significantly associated with the lower GFR category, adjusted for seasons. ROC curve analysis showed that the cutoff point of 25(OH)D of 41 nmol/l was associated with lower GFR [area under the curve (AUC) = 0.694, p = 0.009]. CKD-EPI estimated GFR (eGFR) was not associated with 25(OH)D in any analysis. There was no difference in 25(OH)D levels between patients with elevated UAE as compared with normoalbuminuric ones (44 ± 21 versus 46 ± 19 nmol/l, p = 0.587).
Conclusion: Lower levels of 25(OH)D are associated with decreased GFR in patients with type 2 DM, especially in older patients, with no evidence of interaction with UAE levels.

PMID: 32782774 [PubMed]

Exploring Shared Pathogenesis of Alzheimer's Disease and Type 2 Diabetes Mellitus via Co-expression Networks Analysis.

Curr Alzheimer Res. 2020 Aug 10;:

Authors: Zhu Y, Ding X, She Z, Bai X, Nie Z, Wang F, Wang F, Geng X

Abstract
BACKGROUND: Alzheimer's disease (AD) and Type 2 diabetes mellitus (T2DM) have an increased incidence in modern society. Although increasing evidence has supported the close linkage between these two disorders, the interrelational mechanisms remain to be fully elucidated.
OBJECTIVE: The primary purpose of this study is to explore the shared pathophysiological mechanisms of AD and T2DM.
METHODS: We downloaded the microarray data of AD and T2DM from the Gene Expression Omnibus (GEO) database and constructed co-expression networks by weighted gene co-expression network analysis (WGCNA) to identify gene network modules related to AD and T2DM. Then, gene ontology (GO) and pathway enrichment analysis were performed on the common genes existing in the AD and T2DM related modules by clusterProfiler and DOSE package. Finally, we utilized the STRING database to construct the protein-protein interaction network and found out the hub genes in the network.
RESULTS: Our findings indicated that seven and four modules were the most significant with AD and T2DM, respectively. Functional enrichment analysis showed that AD and T2DM common genes were mainly enriched in signaling pathways such as circadian entrainment, phagosome, glutathione metabolism and synaptic vesicle cycle. Protein-protein interaction network construction identified 10 hub genes (CALM1, LRRK2, RBX1, SLC6A1, TXN, SNRPF, GJA1, VWF, LPL, AGT) in AD and T2DM shared genes.
CONCLUSIONS: Our work identified common pathogenesis of AD and T2DM. These shared pathways might provide a novel idea for further mechanistic studies and hub genes that may serve as novel therapeutic targets for diagnosis and treatment of AD and T2DM.

PMID: 32781959 [PubMed - as supplied by publisher]

Association between serum alkaline phosphatase and renal outcome in patients with type 2 diabetes mellitus.

Ren Fail. 2020 Nov;42(1):818-828

Authors: Zhao L, Li L, Ren H, Zou Y, Zhang R, Wang S, Xu H, Zhang J, Liu F

Abstract
This retrospective study included 299 patients with type 2 diabetes mellitus and biopsy-confirmed diabetic nephropathy (DN) to investigate the prognostic value of alkaline phosphatase (ALP) for renal outcome. Cox proportional hazards models were used to estimate the hazard ratios (HRs) for the serum ALP level on renal outcome, which was defined as end-stage renal disease (ESRD) or a 50% decline in estimated glomerular filtration rate (eGFR) from baseline. The median baseline ALP was 80 IU/L with an interquartile range of 64-97 IU/L. Serum ALP was negatively associated with eGFR but positively associated with proteinuria and renal interstitial fibrosis. During a median follow-up period of 23 months, ESRD or a 50% declined in the eGFR occurred in 156 (52.2%) patients. The highest quartile of ALP was significantly associated with poor renal outcome, as defined above (HR 2.38, 95% confidence interval [CI] 1.09-5.17), when adjusted for sociodemographics, baseline eGFR, proteinuria, liver function parameters, parathyroid hormone levels, and renal pathological findings. Each standard deviation higher in the natural log-transformed ALP was associated with a 25% increased risk for poor renal outcome. Additionally, there was a graded increase in the risk for poor renal outcome with higher ALP in patients with nephrotic-range proteinuria. However, no significant associations were observed between serum ALP levels and renal outcome in patients with non-nephrotic-range proteinuria. In conclusion, an elevated ALP level was independently associated with poor renal outcome in patients with type 2 diabetes mellitus and nephrotic-range proteinuria after multivariate adjustment.

PMID: 32781868 [PubMed - in process]