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Empagliflozin: a new sodium-glucose co-transporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes.

ABSTRACT: Type 2 diabetes is increasing in prevalence worldwide, and hyperglycemia is often poorly controlled despite a number of therapeutic options. Unlike previously available agents, sodium-glucose co-transporter 2 (SGLT2) inhibitors offer an insulin-independent mechanism for improving blood glucose levels, since they promote urinary glucose excretion (UGE) by inhibiting glucose reabsorption in the kidney. In addition to glucose control, SGLT2 inhibitors are associated with weight loss and blood pressure reductions, and do not increase the risk of hypoglycemia. Empagliflozin is a selective inhibitor of SGLT2, providing dose-dependent UGE increases in healthy volunteers, with up to 90 g of glucose excreted per day. It can be administered orally, and studies of people with renal or hepatic impairment indicated empagliflozin needed no dose adjustment based on pharmacokinetics. In Phase II trials in patients with type 2 diabetes, empagliflozin provided improvements in glycosylated hemoglobin (HbA1c) and other measures of glycemic control when given as monotherapy or add-on to metformin, as well as reductions in weight and systolic blood pressure. As add-on to basal insulin, empagliflozin not only improved HbA1c levels but also reduced insulin doses. Across studies, empagliflozin was generally well tolerated with a similar rate of hypoglycemia to placebo; however, patients had a slightly increased frequency of genital infections, but not urinary tract infections, versus placebo. Phase III studies have also reported a good safety profile along with significant improvements in HbA1c, weight and blood pressure, with no increased risk of hypoglycemia versus placebo. Based on available data, it appears that empagliflozin may be a useful option in a range of patients; however, clinical decisions will be better informed by the results of ongoing studies, in particular, a large cardiovascular outcome study (EMPA-REG OUTCOME™).

SUBMITTER: Neumiller JJ

PROVIDER: S-EPMC4079288 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Empagliflozin: a new sodium-glucose co-transporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes.

Neumiller Joshua J JJ

Drugs in context 20140611

Type 2 diabetes is increasing in prevalence worldwide, and hyperglycemia is often poorly controlled despite a number of therapeutic options. Unlike previously available agents, sodium-glucose co-transporter 2 (SGLT2) inhibitors offer an insulin-independent mechanism for improving blood glucose levels, since they promote urinary glucose excretion (UGE) by inhibiting glucose reabsorption in the kidney. In addition to glucose control, SGLT2 inhibitors are associated with weight loss and blood press ...[more]

PMID: 24991224

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Project description:IntroductionThe first cardiovascular safety trial in the sodium-glucose co-transporter-2 (SGLT2) inhibitor drug class, the Empagliflozin Cardiovascular Outcomes and Mortality in Type 2 Diabetes (EMPA-REG OUTCOME) trial, demonstrated significant cardiovascular risk reduction with empagliflozin. It is currently not clear what proportions of people with type 2 diabetes (T2DM) have the same high cardiovascular risk as those included in the trial, and will therefore be likely to experience the same cardiovascular benefit. We aimed to identify and describe the proportion of people with T2DM from a representative English national population who have the comparable high cardiovascular risk to those included in the EMPA-REG trial.MethodA cross-sectional analysis of cardiovascular risk in people with T2DM and a subgroup prescribed SGLT2 inhibitors. Patients were identified from the Royal College of General Practitioners Research and Surveillance Centre database. Cardiovascular risk factors were identified from electronic patient records.ResultsFrom 1,238,909 patients at 128 GP practices, we identified 60,327 adults with T2DM (mean age 66.1 years, SD 13.9) of whom 55.6% were male. From these 1642 (2.7%) people had been initiated on an SGLT2 inhibitor (mean age 58.1 years, SD 10.4; 58.8% male). In the complete T2DM group only 15.7% (95% CI 15.5-16.0%) had the same high cardiovascular risk as those included in the EMPA-REG trial. In those already initiated on SGLT2 inhibitors this proportion was 11.1% (95% CI 9.8-12.4%). Whilst the proportion was higher in the oldest age groups, in those 70+ years old less than a quarter met the EMPA-REG trial high cardiovascular risk criteria.ConclusionsThe EMPA-REG trial results are applicable only to a small proportion of people with T2DM and a smaller proportion of those currently treated with SGLT2 inhibitors. Additional data are required to identify any cardiovascular benefit in people with lower cardiovascular risk.FundingAstraZeneca.

Project description:BackgroundThe treatment duration of insulin-sodium-glucose co-transporter inhibitors (SGLTis) co-treatment of type 1 diabetes mellitus (T1DM) patients in randomized controlled trials (RCTs) varies by 1-52 weeks. Henceforth, treatment duration-wise, we compared the following insulin-treatment adjuncts- mega- versus low-dose SGLTis, SGLTis versus placebo, and different SGLTi dosages.MethodDouble-blinded RCTs reporting the above were searched (using terms like insulin-dependent, "juvenile-onset diabetes," and "sodium glucose cotransport*") in the PubMed, Embase, and Scopus databases and appraised using a Cochrane tool. The risks across different SGLTi-dosages were compared using network meta-analysis. Random-effect pairwise meta-analysis was performed for the remaining harm juxtapositions. Meta-analyses were performed for the following treatment durations- < 4 weeks, 4 to < 24 weeks, and ≥ 24 weeks. For meta-analysis and certainty of evidence assessment, we used the Stata statistical software and the GRADE method, respectively.ResultsA total of 15 (low risks of bias) studies sourcing data from about 7,330 T1DM patients were reviewed. Meta-analysis findings of ≥ 24 weeks long trials were- a. SGLTi-insulin co-treatment increased the genital infection (GI) (RR: 3.51; 95% CI: 2.59, 4.77), diabetic ketoacidosis (DKA) and (RR: 3.25; 95% CI:1.29, 8.16), and serious side effects (RR: 1.43; 95% CI: 1.05, 1.94) risk. b. SGLT2i-insulin increased the GI risk (RR: 3.77; 95% CI: 2.31, 6.16; high-quality evidence). c. Sotagliflozin-insulin increased the GI (RR: 3.36; 95% CI: 2.28, 4.96) and DKA (RR: 6.69; 95% CI: 2.75, 16.32) risk (both high-quality evidence). Compared to low-dose, megadose SGLTi treatment for 4 to < 24 weeks increased the GI risk. The remaining analyses were not statistically significantly different.ConclusionOn moderate to long-term treatment (24-52 weeks) of T1DM patients, insulin-SGLT2i co-treatment was associated with GI risk, and insulin-sotagliflozin co-treatment was associated with DKA and GI risk.Supplementary informationThe online version contains supplementary material available at 10.1007/s40200-023-01192-7.

Dataset Information

Empagliflozin: a new sodium-glucose co-transporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes.

Publications

Empagliflozin: a new sodium-glucose co-transporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes.

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