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Diabetes: Is There a Future for Pharmacogenomics Guided Treatment?

ABSTRACT: Diabetes is a disease defined on the basis of hyperglycemia. There are monogenic forms of diabetes where defining the genetic cause has a dramatic impact on treatment-with patients being able to transition from insulin to sulfonylureas. However, the majority of diabetes is type 2 diabetes. This review outlines the robust evidence accrued to date for pharmacogenetics of metformin, sulfonylureas, thiazolidinediones, and dipeptidyl peptidase-4 inhibitors but highlights that these variants will only be of clinical utility when the genotype is already known at the point of prescribing. The future of pharmacogenetics in diabetes and other common complex disease relies on a paradigm shift-that of preemptive panel genotyping and use of clinical decision support tools to assimilate this genetic information with other clinical phenotypic data and to present this information simply to the prescriber. Given the recent dramatic fall in genotyping costs, this future is not far off.

SUBMITTER: Pearson ER

PROVIDER: S-EPMC6771467 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Diabetes: Is There a Future for Pharmacogenomics Guided Treatment?

Pearson Ewan R ER

Clinical pharmacology and therapeutics 20190801 2

Diabetes is a disease defined on the basis of hyperglycemia. There are monogenic forms of diabetes where defining the genetic cause has a dramatic impact on treatment-with patients being able to transition from insulin to sulfonylureas. However, the majority of diabetes is type 2 diabetes. This review outlines the robust evidence accrued to date for pharmacogenetics of metformin, sulfonylureas, thiazolidinediones, and dipeptidyl peptidase-4 inhibitors but highlights that these variants will only ...[more]

PMID: 31012484

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Project description:Background The implementation of genotyping for anti-hypertensive drugs in clinical practice remains a challenge. We conducted this study to analyze the distribution of polymorphisms of antihypertensive drug-related genes in Changsha County in China and compare the clinical effectiveness of genotype-guided and clinical experience-guided antihypertensive therapy in hypertensive individuals. Methods A total of 9,933 essential hypertensive participants from Changsha County were consecutively enrolled in our study, and 7 genetic polymorphic loci (CYP2D6*10, ADRB1, CYP2C9*3, AGTR1, ACE, CYP3A5*3 and NPPA) were detected by a polymerase chain reaction (PCR)-fluorescence probe. From an available sample of 660 hypertensive participants, 495 cases were randomly identified by genotype-guided therapy and 165 cases by clinical experience-guided therapy. We performed 24-hour ambulatory blood pressure (BP) monitoring on each of these cases, pre- and post-intervention. Results In the enrolled 9,933 cases, the mutation frequencies of CYP2C9*3, ADRB1(1165G>C), AGTR1(1166A>C), CYP2D6*10, ACE(I/D), CYP3A5*3 and NPPA(2238T>C) were 4.41%, 74.60%, 5.55%, 57.08%, 30.94%, 69.03% and 1.19%, respectively. In both genotype-guided and clinical experience-guided groups, the comparisons of intra-group pre-and post-treatments showed significant decreases in diastolic blood pressure (DBP) (P<0.01) and significant increases in the control rate of BP (47.1% vs. 38.6% and 37.5% vs. 33.9%, P<0.05) in response to adjusted antihypertensive agents. Correspondingly, the extent of the reduction of systolic blood pressure (SBP; 3.52±11.72 vs. 0.92±9.14 mmHg), the extent of the increase in the rate of BP control (8.5% vs. 3.6%) and the percentage rate of decrease of grades 2 and 3 hypertensive individuals were more significant in the genotype-guided group than that in the clinical experience-guided group (P<0.01). Conclusions While prescribing anti-hypertensive drugs, appropriate dosage and type adjustments should be made according to the gene mutation frequency and individual circumstances. Pharmacogenomics-guided personalized treatment of hypertensive patients is likely to be a more effective strategy, especially in those with significantly elevated SBP.

Project description:BackgroundIn the treatment of depression, medication plays a crucial role. However, insufficient patient adherence to medication often results in unsatisfactory treatment outcomes, increasing both the recurrence and rehospitalization rates of depression, and consequently imposing a greater economic burden on the healthcare system.ObjectivesOur objective was to examine the impact of pharmacogenomic testing on medication adherence and antidepressant switching rates among individuals diagnosed with depression.MethodsThis retrospective cohort study encompassed patients diagnosed with depression who were admitted to the First Hospital of Hebei Medical University between April 2022 and September 2023. Patients were categorized into a pharmacogenomics-guided treatment (PGxT) group and a treatment as usual (TAU) group based on whether pharmacogenetic testing was conducted. The primary outcome measures included the proportion of patients exhibiting medication adherence greater than 80% at three and 6 months post-discharge, as well as the proportion of patients experiencing changes in their prescribed medication types.ResultsA total of 310 patients in the PGxT group and TAU group were obtained through propensity score matching. Among the 620 patients in both groups, 57.42% demonstrated good adherence (≥80%) at 3 months; this percentage dropped to 31.45% at 6 months. At 3 months of observation, the percentages of patients demonstrating good adherence were significantly different between the groups (64.52% in the PGxT group vs. 50.32% in the TAU group; p < 0.001). The difference was also significant after 6 months (38.06% in the PGxT group vs. 24.84% in the TAU group; p < 0.001). Furthermore, patients receiving PGxT (20.64%) exhibited a lower rate of antidepressant conversion compared to those receiving TAU (31.29%).ConclusionThe findings of this study indicate that pharmacogenomics testing positively influences treatment adherence and may decrease the need to switch medications among patients with depression.

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Diabetes: Is There a Future for Pharmacogenomics Guided Treatment?

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Diabetes: Is There a Future for Pharmacogenomics Guided Treatment?

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