Empagliflozin improves glycemic parameters and cardiovascular risk factors in patients with Type 2 Diabetes (T2DM): Pooled data from four pivotal phase III trials

Hach, Thomas; Gerich, John E.; Salsali, Afshin; Kim, G; Hantel, Stefan; Woerle, HJ; Broedl, UC

doi:10.1055/s-0034-1374999

Cited by 41 publications

(47 citation statements)

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“…The changes in lipid parameters with canagliflozin were generally similar in patients <65 and ≥65 years of age, and were consistent with previous observations in individual Phase 3 studies [9-16]. Similar changes in lipid parameters have been seen with other SGLT2 inhibitors [24,25]. The mechanism for the increase in LDL-C seen with canagliflozin is unknown.…”

Section: Discussionsupporting

confidence: 87%

Efficacy and safety of canagliflozin compared with placebo in older patients with type 2 diabetes mellitus: a pooled analysis of clinical studies

et al. 2014

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BackgroundCanagliflozin is a sodium glucose co-transporter 2 inhibitor developed for the treatment of patients with type 2 diabetes mellitus (T2DM). The efficacy and safety of canagliflozin were evaluated in patients with T2DM <65 and ≥65 years of age.MethodsPooled data from 4 randomised, placebo-controlled, 26-week, Phase 3 studies (N = 2,313) evaluating canagliflozin 100 and 300 mg were analysed by age: <65 years (n = 1,868; mean age, 52.8 years) or ≥65 years (n = 445; mean age, 69.3 years). Efficacy evaluations included change from baseline in glycaemic parameters and systolic blood pressure (BP), and percent change from baseline in body weight. Assessment of safety/tolerability included adverse event (AE) reports, incidence of documented hypoglycaemia, and percent change from baseline in fasting plasma lipids.ResultsCanagliflozin 100 and 300 mg reduced HbA1c and fasting plasma glucose relative to placebo in patients <65 and ≥65 years of age. Both canagliflozin doses reduced body weight and systolic BP relative to placebo in patients <65 and ≥65 years of age. Incidence of overall AEs was similar across all treatment groups in patients <65 and ≥65 years of age. Incidences of serious AEs and AE-related discontinuations were similar across all treatment groups in patients <65 years of age and higher with canagliflozin 100 mg than other groups in patients ≥65 years of age. As in patients <65 years of age, incidences of genital mycotic infections and osmotic diuresis-related AEs were higher with canagliflozin relative to placebo in those ≥65 years of age. Incidences of urinary tract infections (UTIs), renal-related AEs, AEs related to volume depletion, and documented hypoglycaemia episodes were similar across all treatment groups in patients ≥65 years of age; no notable trends were observed with canagliflozin 100 and 300 mg relative to placebo in these AEs among patients <65 years of age. Changes in lipid parameters with canagliflozin were similar in both age subsets.ConclusionsCanagliflozin improved glycaemic control, body weight, and systolic BP, and was generally well tolerated in older patients with T2DM.Trial registrationClinicalTrials.gov, NCT01081834; NCT01106677; NCT01106625; NCT01106690.

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Section: Discussionsupporting

confidence: 87%

Efficacy and safety of canagliflozin compared with placebo in older patients with type 2 diabetes mellitus: a pooled analysis of clinical studies

et al. 2014

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“…However, it remains unclear whether SGLT-2 inhibitors prevent cardiovascular events in cardiovascular disease-free diabetic patients. Several clinical studies have revealed that SGLT-2 inhibitors decrease plasma triglyceride (TG) levels and increase high-density lipoprotein (HDL)-cholesterol (C) (HDL-C) levels, but also increase low-density lipoprotein (LDL)-C (LDL-C) levels [5, 6]. LDL-C is the most powerful determinant of cardiovascular events in patients with type 2 diabetes [7, 8], thus, the increased levels of LDL-C associated with SGLT-2 inhibitor use might increase cardiovascular risk.…”

Section: Introductionmentioning

confidence: 99%

Dapagliflozin decreases small dense low-density lipoprotein-cholesterol and increases high-density lipoprotein 2-cholesterol in patients with type 2 diabetes: comparison with sitagliptin

Hayashi

Fukui

Nakanishi

et al. 2017

Cardiovasc Diabetol

137

104

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BackgroundThe sodium-glucose co-transporter-2 (SGLT-2) inhibitors have been reported to increase both low-density lipoprotein (LDL) and high-density lipoprotein (HDL)-cholesterol (C). This study aimed to determine how SGLT-2 inhibitors affect LDL and HDL-C subspecies.MethodsThis single center, open-label, randomized, prospective study included 80 patients with type 2 diabetes taking prescribed oral hypoglycemic agents. Patients were allocated to receive dapagliflozin (n = 40) or sitagliptin (n = 40) as add-on treatment. Fasting blood samples were collected before and 12 weeks after this intervention. Small dense (sd) LDL-C, large buoyant (lb) LDL-C, HDL2-C, and HDL3-C levels were determined using our established homogeneous assays. Statistical comparison of blood parameters before and after treatment was performed using the paired t test.ResultsDapagliflozin and sitagliptin comparably decreased HbA1c (0.75 and 0.63%, respectively). Dapagliflozin significantly decreased body weight, systolic blood pressure, plasma triglycerides and liver transaminases, and increased adiponectin; sitagliptin did not alter these measurements. LDL-C and apolipoprotein (apo) B were not significantly changed by dapagliflozin, whereas HDL-C and apo AI were increased. Dapagliflozin did not alter concentrations of LDL-C, but sd LDL-C decreased by 20% and lb LDL-C increased by 18%. Marked elevation in lb LDL-C (53%) was observed in individuals (n = 20) whose LDL-C was elevated by dapagliflozin. However, sd LDL-C remained suppressed (20%). Dapagliflozin increased HDL2-C by 18% without affecting HDL3-C. Sitagliptin did not alter plasma lipids or lipoprotein subspecies.ConclusionsA SGLT-2 inhibitor, dapagliflozin suppresses potent atherogenic sd LDL-C and increased HDL2-C, a favorable cardiometabolic marker. Although LDL-C levels are elevated by treatment with dapagliflozin, this was due to increased concentrations of the less atherogenic lb LDL-C. However, these findings were not observed after treatment with dipeptidyl peptidase-4 inhibitor, sitagliptin. Trial registration UMIN Clinical Trials Registry (UMIN000020984)Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-016-0491-5) contains supplementary material, which is available to authorized users.

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“…29 Similar changes in lipid parameters have been reported for other SGLT2 inhibitors relative to placebo in patients with T2DM. 24,30 Because LDL-C is an established cardiovascular risk factor and an accepted surrogate endpoint, the impact of these changes are currently under evaluation in a larger cardiovascular assessment study. 31 Generally, minimal differences in safety laboratory parameters were observed between canagliflozin and placebo across the placebo-controlled studies.…”

Section: Discussionmentioning

confidence: 99%

Safety and Tolerability of Canagliflozin in Patients With Type 2 Diabetes Mellitus: Pooled Analysis of Phase 3 Study Results

Usiskin

Kline

Fung

et al. 2014

Postgraduate Medicine

172

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Empagliflozin improves glycemic parameters and cardiovascular risk factors in patients with Type 2 Diabetes (T2DM): Pooled data from four pivotal phase III trials

Cited by 41 publications

References 0 publications

Efficacy and safety of canagliflozin compared with placebo in older patients with type 2 diabetes mellitus: a pooled analysis of clinical studies

Efficacy and safety of canagliflozin compared with placebo in older patients with type 2 diabetes mellitus: a pooled analysis of clinical studies

Dapagliflozin decreases small dense low-density lipoprotein-cholesterol and increases high-density lipoprotein 2-cholesterol in patients with type 2 diabetes: comparison with sitagliptin

Safety and Tolerability of Canagliflozin in Patients With Type 2 Diabetes Mellitus: Pooled Analysis of Phase 3 Study Results

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