Efficacy and safety of empagliflozin for type 2 diabetes: a systematic review and meta‐analysis

Liakos, Aris; Karagiannis, Thomas; Athanasiadou, Eleni; Sarigianni, Maria; Mainou, Maria; Παπαθεοδώρου, Κωνσταντίνος; Bekiari, Eleni; Τσάπας, Απόστολος

doi:10.1111/dom.12307

Cited by 193 publications

(165 citation statements)

References 39 publications

(128 reference statements)

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“…The compensatory increase in EGP that occurs with empagliflozin treatment may attenuate the reduction in hyperglycaemia that would be predicted from the increase in UGE, although increases in food intake may also contribute [33]. The observed shift in substrate oxidation from carbohydrate to fat is consistent with the weight loss that has been observed in clinical trials of empagliflozin [14]. The hormonal changes, increased lipolysis and fat oxidation are the metabolic background for the increase in ketone bodies described in a small number of patients receiving SGLT2 inhibitor therapy [34].…”

Section: Discussionsupporting

confidence: 63%

“…SGLT2 inhibitors lower fasting and postprandial glycaemia by enhancing urinary glucose excretion (UGE), a mechanism that is independent of insulin secretion [13]. For this reason, SGLT2 inhibitors can be used in association with other antihyperglycaemic agents including dipeptidyl peptidase 4 inhibitors, metformin and insulin [14][15][16]. In particular, empagliflozin as add-on to metformin has been shown to improve HbA 1c and fasting plasma glucose levels for up to 78 weeks [17][18][19].…”

Section: Introductionmentioning

confidence: 99%

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Metabolic consequences of acute and chronic empagliflozin administration in treatment-naive and metformin pretreated patients with type 2 diabetes

et al. 2015

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Aims/hypothesis Sodium glucose co-transporter 2 (SGLT2) inhibitors lower glycaemia by inducing glycosuria, but raise endogenous glucose production (EGP). Metformin lowers glycaemia mainly by suppressing EGP. We compared the effects of the SGLT2 inhibitor empagliflozin in treatment-naive (TN) and metformin pretreated (Met) patients with type 2 diabetes. Methods A total of 32 TN and 34 patients on a stable dose of metformin, two subgroups of a study that we previously reported, received a mixed meal with double-tracer glucose administration and indirect calorimetry at baseline, after a single 25 mg dose of empagliflozin, and after 4 weeks of treatment with empagliflozin 25 mg/day. Results At baseline, compared with the TN group, the Met group had higher fasting glycaemia (9.1 ± 1.7 vs 8.2 ± 1.3 mmol/l), lower fasting and postmeal insulin secretion, lower beta cell glucose sensitivity (37 [18]

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Section: Discussionsupporting

confidence: 63%

Section: Introductionmentioning

confidence: 99%

Metabolic consequences of acute and chronic empagliflozin administration in treatment-naive and metformin pretreated patients with type 2 diabetes

et al. 2015

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“…In the meta‐analysis, the incidence of UTIs did not increase with empagliflozin 10 or 25 mg relative to placebo [ORs (95% CI), 1.20 (0.92–1.57) and 1.03 (0.81 to 1.32)] 46. However, genital infections were observed in a greater proportion of patients treated with empagliflozin than in those receiving placebo [ORs (95% CI), 4.39 (2.10–9.19) with 10 mg and 3.31 (1.55–7.09) with 25 mg] 46.…”

Section: Empagliflozinmentioning

confidence: 98%

“…This observation is likely because of caloric loss following glycosuria. In a meta‐analysis of RCTs (10 trials, n = 6203), empagliflozin 25 mg showed a significant reduction in body weight [weighted mean difference; WMD (95% CI), −1.84 kg (−2.30 to −1.38)] and no increased risk of hypoglycaemia [odds ratio; OR (95% CI), 1.10 (0.87–1.39)] vs. placebo 46.…”

Section: Empagliflozinmentioning

confidence: 99%

Empagliflozin/linagliptin single‐tablet combination: first‐in‐class treatment option

Woo

2015

Int J Clin Pract

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SummaryBackgroundThe availability of a dual sodium glucose co‐transporter 2/dipeptidyl peptidase‐4 inhibitor combination in a single‐tablet combination (STC) represents a new therapeutic option for patients with type 2 diabetes. Empagliflozin/linagliptin STC has been recently approved by the US Food and Drug Administration for the treatment of type 2 diabetes mellitus (T2DM).AimThe aim of this study was to describe the latest clinical evidence on the efficacy and safety profiles of empagliflozin/linagliptin STCs in comparison with the individual components. Juxtaposition of the STC with dapagliflozin/saxagliptin combination was also presented.ResultsEmpagliflozin/linagliptin STC given as initial therapy or on metformin background lowered mean glycated haemoglobin (HbA1c) by approximately 1.1% (mean baseline HbA1c, 8.0%). Furthermore, the STC reduced mean body weight by 2.0–3.0 kg from baseline. With the STC treatment, no confirmed incidents of hypoglycaemia were reported in drug‐naïve patients; in patients taking metformin hypoglycaemia occurred at low rates which were comparable with monotherapy. Use of STCs in the treatment of T2DM can simplify drug dosing regimen, reduce pill burden and increase treatment adherence. Empagliflozin/linagliptin STC is a combination that offers potential additional benefits such as body weight loss and moderate reductions in blood pressure, without increasing risk of hypoglycaemia.ConclusionEmpagliflozin/linagliptin STC appears to be a rational choice for a wide range of patients in need of multiple agents for controlling hyperglycaemia. The STC should be particularly useful in patients in whom hypoglycaemia, weight gain and treatment adherence are of concern.

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“…Older meta-analyses focused on intermediate outcomes of empagliflozin when compared with placebo; e.g., HbA1c, blood pressure, and body weight (7)(8)(9)(10)(11)(12)(13)(14)(15). The most recent high-quality meta-analyses included 13 (6) and 16 (5) randomized controlled trials (RCTs) that reported mortality and morbidity in adults with type 2 diabetes treated with empagliflozin but did not examine the comparative effectiveness of empagliflozin and other specific antidiabetic drugs (5,6).…”

Section: Introductionmentioning

confidence: 99%

Comparative effectiveness and safety of empagliflozin on cardiovascular mortality and morbidity in adults with type 2 diabetes

Aronow¹,

Shamliyan²

2017

Ann. Transl. Med.

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Background: Based on a single placebo-controlled randomized clinical trial, empagliflozin is licensed to reduce cardiovascular death in diabetes and comorbid cardiovascular disease. Methods:We examined the comparative effectiveness of empagliflozin on mortality and cardiovascular morbidity in type 2 diabetes. We conducted random-effects direct frequentist meta-analyses of aggregate data and appraised the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Our search in PubMed, EMBASE, the Cochrane Library, patients). Two network meta-analyses concluded that sodium-glucose cotransporter 2 (SGLT2) inhibitors, mostly due to empagliflozin, decrease all-cause and cardiovascular mortality but increase the risk of nonfatal stroke, genital infection, and volume depletion. Conclusions:We conclude that empagliflozin reduces all-cause and cardiovascular mortality in patients with established cardiovascular disease and type 2 diabetes. Sparse direct evidence suggests no difference in mortality between empagliflozin and metformin, glimepiride, linagliptin, or sitagliptin. Long-term comparative safety needs to be established.

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Efficacy and safety of empagliflozin for type 2 diabetes: a systematic review and meta‐analysis

Abstract: Empagliflozin effectively lowers blood glucose and provides additional clinical benefits including body weight and blood pressure reduction. Ongoing trials will elucidate the long-term safety and effect of empagliflozin on cardiovascular outcomes.

Cited by 193 publications

References 39 publications

Metabolic consequences of acute and chronic empagliflozin administration in treatment-naive and metformin pretreated patients with type 2 diabetes

Metabolic consequences of acute and chronic empagliflozin administration in treatment-naive and metformin pretreated patients with type 2 diabetes

Empagliflozin/linagliptin single‐tablet combination: first‐in‐class treatment option

Comparative effectiveness and safety of empagliflozin on cardiovascular mortality and morbidity in adults with type 2 diabetes

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