Dataset Information

Pilot study in pharmacogenomic management of empagliflozin in type 2 diabetes mellitus patients.

ABSTRACT:

Background

Type 2 diabetes mellitus (T2DM) is a metabolic disorder in which the patients with high blood sugar develop insufficient insulin secretion or insulin resistance. The solute carrier family, 5 member 2 (SLC5A2) gene is a member of sodium/glucose transporter family which can reduce heart and kidney problems. The current study aims to look into any association between rs11646054 variant in SLC5A2 gene and the anti-diabetic efficacy and safety of empagliflozin.

Methods

14 T2DM who failed to respond to previous treatments, empagliflozin 10 mg was added for 6 months. Genotyping of the rs11646054 variant of SLC5A2 gene was performed by polymerase chain reaction (PCR) followed by Sanger sequencing.

Results

Although hemoglobin A1c (HbA1c) and low-density lipoprotein (LDL) were not significantly different, but the mean fasting blood sugar (FBS), 2-h post prandial (2hpp), albumin-to-creatinine ratio (ACR), and total cholesterol (TC) were significantly decreased after 6 months empagliflozin treatment. There was a significant difference in the mean final reductions in FBS level among genotypes. It's important to mention that those who were GG homozygotes had a tendency to have more decrements.

Conclusions

The study results indicate that effects of variation in SLC5A2 (rs11646054) on the clinical efficacy of empagliflozin were negligible.

SUBMITTER: Jamalizadeh M

PROVIDER: S-EPMC8630276 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Publications

Pilot study in pharmacogenomic management of empagliflozin in type 2 diabetes mellitus patients.

Jamalizadeh Mahdieh M Hasanzad Mandana M Sarhangi Negar N Sharifi Farshad F Nasli-Esfahani Ensieh E Larijani Bagher B

Journal of diabetes and metabolic disorders 20210810 2

<h4>Background</h4>Type 2 diabetes mellitus (T2DM) is a metabolic disorder in which the patients with high blood sugar develop insufficient insulin secretion or insulin resistance. The <i>solute carrier family, 5 member 2 (SLC5A2)</i> gene is a member of sodium/glucose transporter family which can reduce heart and kidney problems. The current study aims to look into any association between rs11646054 variant in <i>SLC5A2</i> gene and the anti-diabetic efficacy and safety of empagliflozin.<h4>Met ...[more]

PMID: 34900792

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Project description:IntroductionThe aim of this analysis was to characterize the safety and tolerability of empagliflozin in patients with type 2 diabetes mellitus (T2DM) who were randomized to empagliflozin (10/25 mg) or placebo in clinical trials.MethodsPooled data from 20 trials were analyzed for patients with T2DM treated with empagliflozin 10 mg (n = 4858), empagliflozin 25 mg (n = 5057), or placebo (n = 4904). The dataset comprised 15 randomized phase I-III trials, an extension trial and dose escalation studies. Adverse events (AEs) were assessed descriptively in participants who took ≥ 1 dose of study drug. AE incidence rates per 100 patient-years were calculated to adjust for differences in drug exposure between trials.ResultsTotal exposure was 16,480 and 7857 patient-years in the pooled empagliflozin 10/25 mg and placebo groups, respectively. The incidence of any AEs, AEs leading to treatment discontinuation, severe AEs, and serious AEs was similar across groups. The frequency of serious AEs requiring hospitalization was 18.6% for the empagliflozin 10/25 mg group and 21.3% for the placebo group. The empagliflozin 10/25 mg group was not associated with a higher rate of confirmed hypoglycemia versus placebo, except in patients co-administered insulin and/or a sulfonylurea (31.5% vs. 30.2%, respectively). The incidence of events consistent with urinary tract infections (UTI) was also similar for the empagliflozin 10/25 mg group versus placebo (9.27 vs. 9.70/100 patient-years, respectively). History of UTI was identified as a risk factor for UTI during treatment. Events consistent with genital infections occurred more frequently with empagliflozin 10/25 mg than placebo (3.54 vs. 0.95/100 patient-years, respectively). The frequency of AEs consistent with volume depletion was similar across groups, but higher with empagliflozin 10/25 mg than placebo in patients aged 75 to < 85 years and those on loop diuretics at baseline.ConclusionThis comprehensive analysis confirms that both empagliflozin 10 mg and 25 mg are well tolerated in patients with T2DM, reinforcing the established clinical safety profile of empagliflozin.

Project description:OBJECTIVE:To update clinicians with an overview of empagliflozin for the treatment of type 2 diabetes mellitus (T2DM), with focus on use in combination regimens. METHODS:Keyword searches were conducted in the Medline database to identify literature reporting clinical trials of at least 12 weeks' duration using empagliflozin treatment in patients with T2DM. RESULTS:When given as monotherapy or in combination therapy (as add-on or single-pill therapy) with metformin, pioglitazone, sulfonylurea, linagliptin, and insulin, empagliflozin produced clinically meaningful reductions in glycated hemoglobin levels, plasma glucose concentrations, bodyweight, and blood pressure. These changes were sustained during long-term treatment. In a dedicated cardiovascular event trial, empagliflozin on top of standard of care demonstrated a significant reduction in the risk of cardiovascular mortality and all-cause mortality. Across the clinical trials, empagliflozin combination therapies were well tolerated, and empagliflozin used alone was not associated with increased risk of hypoglycemia versus placebo. Indeed, the combination of empagliflozin and metformin had a significantly reduced rate of hypoglycemia compared with the combination of metformin and a sulfonylurea. On the other hand, empagliflozin treatment did have increased risk of genital infections compared with placebo. In clinical trials to date, diabetic ketoacidosis was not seen more frequently with empagliflozin than with placebo, but physicians should be alert to the possibility of this rare event. CONCLUSION:Empagliflozin has the potential to make an important contribution to the treatment of patients with T2DM. In some patients, empagliflozin may be used as monotherapy, but it is most likely to be used in combination with other therapies. Given the reduced risk of mortality seen when empagliflozin was added to standard care in patients at high cardiovascular risk, as well as the lack of alternative options for patients at lower cardiovascular risk, empagliflozin may be added to ongoing regimens for a significant proportion of patients.

Project description:BACKGROUND:Deteriorated arterial function and high incidence of cardiovascular events characterise diabetes mellitus. Metformin and recent antidiabetic drugs, SGLT2 inhibitors, reduce cardiovascular events. We explored the possible effects of empagliflozin's effect on top of metformin treatment on endothelial function and arterial stiffness parameters in type 1 diabetes mellitus (T1DM) patients. METHODS:Forty T1DM patients were randomised into three treatment groups: (1) empagliflozin (25 mg daily), (2) metformin (2000 mg daily) and (3) empagliflozin/metformin (25 mg daily and 2000 mg daily, respectively). The fourth group received placebo. Arterial function was assessed at inclusion and after 12 weeks treatment by: endothelial function [brachial artery flow-mediated dilation (FMD), reactive hyperaemia index (RHI)], arterial stiffness [pulse wave velocity (PWV) and common carotid artery stiffness (?-stiffness)]. For statistical analysis one-way analysis of variance with Bonferroni post-test was used. RESULTS:Empagliflozin on top of metformin treatment significantly improved endothelial function as did metformin after 12 weeks of treatment: FMD [2.6-fold (P?<?0.001) vs. 1.8-fold (P?<?0.05)] and RHI [1.4-fold (P?<?0.01) vs. 1.3-fold (P?<?0.05)]. Empagliflozin on top of metformin treatment was superior to metformin in improving arterial stiffness parameters; it significantly improved PWV and ?-stiffness compared to metformin [by 15.8% (P?<?0.01) and by 36.6% (P?<?0.05), respectively]. Metformin alone did not influence arterial stiffness. CONCLUSION:Empagliflozin on top of metformin treatment significantly improved arterial stiffness compared to metformin in T1DM patients. Endothelial function was similarly improved in all treatment groups. Empagliflozin seems to possess a specific capacity to decrease arterial stiffness, which could support its cardioprotective effects observed in large clinical studies. Trial registration Clinical trial registration: NCT03639545.

Project description:Sodium glucose cotransporter 2 (SGLT2) inhibitors have a unique mechanism of action leading to excretion of glucose in the urine and subsequent lowering of plasma glucose. This mechanism is independent of ?-cell function; thus, these agents are effective treatment for type 2 diabetes mellitus (T2DM) at theoretically any disease stage. This class should not confer an additional risk of hypoglycemia (unless combined with insulin or an insulin secretagogue) and has the potential to be combined with other classes of glucose-lowering agents. Empagliflozin is one of three currently approved SGLT2 inhibitors in the United States, and has shown a favorable benefit-risk ratio in phase 3 clinical trials as monotherapy and as add-on to other glucose-lowering therapy in broad patient populations. In addition to its glucose-lowering effects, empagliflozin has been shown to reduce body weight and blood pressure without a compensatory increase in heart rate. Moreover, on top of standard of care, empagliflozin is the first glucoselowering agent to demonstrate cardiovascular risk reduction in patients at high risk of cardiovascular disease in a prospective outcomes trial: a 14% reduction in risk of the 3-point composite endpoint of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Like other SGLT2 inhibitors, empagliflozin is associated with a higher rate of genital mycotic infections than placebo and has the potential for volume depletion-associated events.This review summarizes the empagliflozin phase 3 clinical trials program and its potential significance in the treatment of patients with T2DM. Evidence from these clinical trials show reductions in glycated hemoglobin (-0.59 to -0.82%) with a low risk of hypoglycemia except when used with insulin or insulin secretagogues, and moderate reductions in body weight (-2.1 to - 2.5 kg) and systolic blood pressure (-2.9 to -5.2 mm Hg), thus supporting the use of empagliflozin as monotherapy or in addition to other glucose-lowering agents. In addition, evidence from the recent EMPA-REG OUTCOME study, which demonstrated relative risk reductions in major adverse cardiac events (14%), cardiovascular mortality (38%) and all-cause mortality (32%), as well as hospitalization for heart failure (36%), supports use of empagliflozin in patients with T2DM and increased cardiovascular risk.

Dataset Information

Pilot study in pharmacogenomic management of empagliflozin in type 2 diabetes mellitus patients.

Background

Methods

Results

Conclusions

Publications

Pilot study in pharmacogenomic management of empagliflozin in type 2 diabetes mellitus patients.

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