Dapagliflozin compared with other oral anti‐diabetes treatments when added to metformin monotherapy: a systematic review and network meta‐analysis

Goring, Sarah; Hawkins, Neil; Wygant, Gail; Roudaut, M.; Townsend, Rebecca; Wood, Ian C.; Barnett, A H

doi:10.1111/dom.12239

Cited by 87 publications

(70 citation statements)

References 51 publications

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“…Consistent with previous findings from other laboratories (15,16,17,18), we demonstrated that sitagliptin lowered the HbA1c, FPG concentration, 2hPG, FAT (%), FFA, serum TG, and HOMA-IR in nT2DM patients. As expected, treatment with sitagliptin led to a small decrease from baseline in body weight, with no significant difference compared with the placebo group.…”

Section: Discussionsupporting

confidence: 93%

Effects of sitagliptin on circulating zinc-α2-glycoprotein levels in newly diagnosed type 2 diabetes patients: a randomized trial

Tian¹,

Liang²,

Liu³

et al. 2016

European Journal of Endocrinology

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Objective: Zinc-a 2 -glycoprotein (ZAG) has recently been characterized as a potent metabolic regulator. However, the effects of anti-diabetic agents on circulating ZAG levels in humans remain largely unknown. To explore the possible mechanisms by which the dipeptidyl peptidase-IV (DPP-IV) inhibitor improves insulin resistance, we investigated the effect of sitagliptin, a DPP-IV inhibitor, on circulating cytokine levels in newly diagnosed type 2 diabetes (nT2DM) patients. Design and methods: A subset of 141 subjects with nT2DM were assigned to receive placebo (nZ47) or sitagliptin (nZ94) for 3 months. Before and after treatment, subjects received a 75 g oral glucose tolerance test, euglycemic-hyperinsulinemic clamp (EHC), and measurement of ZAG and adiponectin (ADI) concentrations. Results: Circulating ZAG levels were lower in nT2DM than in control individuals (P!0.01). After 3 months of sitagliptin treatment, HbA1c, fasting plasma glucose, postprandial glucose, 2-h insulin after glucose overload, triglycerides, and homeostasis model assessment of insulin resistance (HOMA-IR) were decreased significantly compared with pre-treatment (P!0.05 or P!0.01), whereas the glucose infusion rate during the stable period of the clamp (M values) during EHC were significantly increased (P!0.01). In addition, circulating ZAG and ADI concentrations were significantly increased along with improved glucose metabolism and insulin sensitivity compared with pre-treatment (both P!0.01) and the change of ZAG (DZAG) was positively associated with DADI, DHOMA-IR, DBMI, Dfasting insulin and negatively associated with D tumor necrosis factor-a (TNF-a). Furthermore, sitagliptin treatment resulted in significantly lowered plasma TNF-a level (P!0.05). Conclusion: A low level of circulating ZAG is associated with insulin resistance and sitagliptin treatment significantly increases circulating ZAG levels. These observations have implications in relation to the mode of action of the DPP-IV inhibitor as an insulin sensitizing agent.

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Section: Discussionsupporting

confidence: 93%

Effects of sitagliptin on circulating zinc-α2-glycoprotein levels in newly diagnosed type 2 diabetes patients: a randomized trial

Tian¹,

Liang²,

Liu³

et al. 2016

European Journal of Endocrinology

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“…Per il trattamento con insulina in monoterapia o insulina combinata con gli altri antidiabetici orali è stata stimata un'incidenza annuale di eventi ipoglicemici severi pari a 2,44% nel caso di insulina basale e a 5,04% per l'insulina basal-bolus (17,18). Per i trattamenti con gli altri antidiabetici orali senza associazione a insulina, sulfaniluree o repaglinide, è stata assunta un'incidenza annuale di eventi ipoglicemici severi pari a zero (18)(19)(20). Il costo unitario per la gestione di un evento ipoglicemico severo è stato considerato pari a €1.911,18 sulla base di uno studio osservazionale italiano in cui sono stati analizzati 3516 eventi di ipoglicemia grave, di cui il 33,1% aveva richiesto ospedalizzazione (21).…”

Section: Dati Dell'analisiunclassified

Analisi di Impatto Sul Budget di Empagliflozin Nel Trattamento Dei Pazienti Con Diabete di tipo 2 e Malattia Cardiovascolare Accertata

Iannazzo

Maggioni

Mannucci

2017

Global & Regional Health Technology Assessment

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ORIGINAL RESEARCH ARTICLElivello di glucosio nel sangue nel DT2 porta nel tempo a gravi danni a cuore, vasi sanguigni, occhi, rene e nervi. Le cause del DT2 sono principalmente l'obesità e l'inattività fisica, e si prevede che nel 2030 la malattia diverrà la settima causa di morte nel mondo (3). Il DT2 viene trattato con dieta, attività fisica, farmaci antidiabetici e somministrazione di insulina, in funzione della progressione della malattia.Empagliflozin è un inibitore specifico e reversibile del cotrasportatore sodio-glucosio di tipo 2 (sodium-glucose cotransporter 2, SGLT2) che ha bassa affinità ma alta capacità di trasportare glucosio. Esso è altamente espresso nel tubulo prossimale renale ed è responsabile del 90% del riassorbimento di glucosio che avviene nel segmento contorto del tubulo prossimale del rene (il restante 10% è riassorbito dagli SGLT1 nel segmento rettilineo del tubulo prossimale). Questo meccanismo di riassorbimento del glucosio è alterato nel paziente con DT2. Il co-trasportatore SGLT2, infatti, è sovraespresso a livello renale nei pazienti con DT2 rispetto ai soggetti senza diabete, e anche la sua attività di riassorbimento del glucosio è aumentata. Questo determina nei pazienti con DT2 e iperglicemia un aumento della quantità di glucosio che

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“…In addition to obvious defects in neuromuscular junction (NMJ) maturation, decreased SMN results in early abnormalities in synaptic input from muscle fibers to motor neurons within the spinal cord (2,3). Both SMA mouse models and severely affected human infants exhibit abnormalities in myofiber maturation, muscle size, and muscle function (4)(5)(6). Furthermore, there is evidence that SMN-intrinsic defects in Schwann cells promote SMA pathogenesis, and peripheral nerve myelination is abnormal in severely affected infants (7).…”

Section: Smn-targeted Therapeutics: the Hope And The Hypementioning

confidence: 99%

Paradoxical insights into whole body metabolic adaptations following SGLT2 inhibition

Cefalu¹

2014

J. Clin. Invest.

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Dapagliflozin compared with other oral anti‐diabetes treatments when added to metformin monotherapy: a systematic review and network meta‐analysis

Abstract: Compared with DPP-4 inhibitors, TZDs and sulphonylureas, dapagliflozin offers similar HbA1c control after 1 year, with similar or reduced risk of hypoglycaemia and the additional benefit of weight loss, when added to metformin.

Cited by 87 publications

References 51 publications

Effects of sitagliptin on circulating zinc-α2-glycoprotein levels in newly diagnosed type 2 diabetes patients: a randomized trial

Effects of sitagliptin on circulating zinc-α2-glycoprotein levels in newly diagnosed type 2 diabetes patients: a randomized trial

Analisi di Impatto Sul Budget di Empagliflozin Nel Trattamento Dei Pazienti Con Diabete di tipo 2 e Malattia Cardiovascolare Accertata

Paradoxical insights into whole body metabolic adaptations following SGLT2 inhibition

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