Po199 a Randomized, Placebo-Controlled, Double-Blind, Phase 3 Trial to Evaluate the Efficacy and Safety of Anagliptin in Patients With Type 2 Diabetes

Yang, Hannah; Lee, S.H.; Min, Kang; Park, S.W.; Chung, Chelsea; Park, K.S.; Choi, Seonghoon; Song, Ki‐Ho; Kim, D.-M.; Lee, M.-K.; Sung, Young–Hoon; Baik, Sei-Hyun; Kim, I.J.; Cha, Boseok; Park, J.H.; Ahn, Y.; Lee, I.-K.; Yoo, Soon Jib; Kim, J.T.; Park, I.B.; Park, T.S.; Yoon, Kun‐Ho

doi:10.1016/s0168-8227(14)70493-0

Cited by 2 publications

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“…Of the 22 089 hits retrieved from our search, 144 studies met our inclusion criteria (Figure ). An agreement value ( κ ) of 80% was achieved for studies requiring detailed analysis and extraction.…”

Section: Resultsmentioning

confidence: 99%

Risk of any hypoglycaemia with newer antihyperglycaemic agents in patients with type 2 diabetes: A systematic review and meta‐analysis

Kamalinia

Josse

Donio

et al. 2019

Endocrino Diabet & Metabol

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Objectives: For patients with type 2 diabetes, newer antihyperglycaemic agents (AHA), including the dipeptidyl peptidase IV inhibitors (DPP4i), glucagon-like peptide-1 receptor agonists (GLP1RA) and sodium glucose co-transporter 2 inhibitors (SGLT2i) offer a lower risk of hypoglycaemia relative to sulfonylurea or insulin.However, it is not clear how AHA compare to placebo on risk of any hypoglycaemia.This study evaluates the risk of any and severe hypoglycaemia with AHA and metformin relative to placebo. Design: A systematic review and meta-analysis was conducted of randomized, placebo-controlled trials ≥12 weeks in duration. MEDLINE, Embase and the Cochrane Library were searched up to April 16, 2019. Studies allowing use of other diabetes medications were excluded. Mantel-Haenszel risk ratio with 95% confidence intervals were used to pool estimates based on class of AHA and number of concomitant therapies used.Patients: Eligible studies enrolled patients with type 2 diabetes ≥18 years of age.Results: 144 studies met our inclusion criteria. Any hypoglycaemia was not increased with AHA when used as monotherapy (DPP4i (RR 1.12; 95% CI 0.81-1.56), GLP1RA (1.77; 0.91-3.46), SGLT2i (1.34; 0.83-2.15)), or as add-on to metformin (DPP4i (0.95; 0.67-1.35), GLP1RA (1.24; 0.80-1.91), SGLT2i (1.29; 0.91-1.83)) or as triple therapy (1.13; 0.67-1.91). However, metformin monotherapy (1.73; 1.02-2.94) and dual therapy initiation (3.56; 1.79-7.10) was associated with an increased risk of any hypoglycaemia. Severe hypoglycaemia was rare not increased for any comparisons. Conclusions:Metformin and the simultaneous initiation of dual therapy, but not AHA used alone or as single add-on combination therapy, was associated with an increased risk of any hypoglycaemia relative to placebo. K E Y W O R D S diabetes mellitus, type 2, dipeptidyl peptidase IV inhibitor, glucagon-like peptide-1 receptor agonist, hypoglycaemia, sodium glucose co-transporter 2 inhibitor S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section. How to cite this article: Kamalinia S, Josse RG, Donio PJ, Leduc L, Shah BR, Tobe SW. Risk of any hypoglycaemia with newer antihyperglycaemic agents in patients with type 2 diabetes: A systematic review and meta-analysis. Endocrinol Diab Metab. 2020;3:e00100. https ://doi.

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Section: Resultsmentioning

confidence: 99%

Risk of any hypoglycaemia with newer antihyperglycaemic agents in patients with type 2 diabetes: A systematic review and meta‐analysis

Kamalinia

Josse

Donio

et al. 2019

Endocrino Diabet & Metabol

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“…These data suggest that GLP-1 may improve skeletal muscle glucose uptake through activating eNOS in the endothelial cells. As physiological GLP-1 is easily degraded by dipeptidyl peptidase-4 (DPP-4) [14,15], DPP-4 inhibitors that induce GLP-1 activation have been used in the treatment of type 2 diabetes [16][17][18][19][20][21]. In addition to exerting actions mediated by GLP-1, DPP-4 inhibitors have been shown to inhibit cleavage of several non-incretin substrates, such as cytokines, chemokines and neuropeptides [22][23][24]; thus, DPP-4 inhibitors may have additional actions independent of those mediated by GLP-1.…”

Section: Introductionmentioning

confidence: 99%

Anagliptin increases insulin-induced skeletal muscle glucose uptake via an NO-dependent mechanism in mice

Satō

Kubota

et al. 2016

Diabetologia

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Aims/hypothesis Recently, incretin-related agents have been reported to attenuate insulin resistance in animal models, although the underlying mechanisms remain unclear. In this study, we investigated whether anagliptin, the dipeptidyl peptidase 4 (DPP-4) inhibitor, attenuates skeletal muscle insulin resistance through endothelial nitric oxide synthase (eNOS) activation in the endothelial cells. We used endothelium-specific Irs2-knockout (ETIrs2KO) mice, which show skeletal muscle insulin resistance resulting from a reduction of insulin-induced skeletal muscle capillary recruitment as a consequence of impaired eNOS activation. Methods In vivo, 8-week-old male ETIrs2KO mice were fed regular chow with or without 0.3% (wt/wt) DPP-4 inhibitor for 8 weeks to assess capillary recruitment and glucose uptake by the skeletal muscle. In vitro, human coronary arterial endothelial cells (HCAECs) were used to explore the effect of glucagon-like peptide 1 (GLP-1) on eNOS activity. Results Treatment with anagliptin ameliorated the impaired insulin-induced increase in capillary blood volume, interstitial insulin concentration and skeletal muscle glucose uptake in ETIrs2KO mice. This improvement in insulin-induced glucose uptake was almost completely abrogated by the GLP-1 receptor (GLP-1R) antagonist exendin-(9-39). Moreover, the increase in capillary blood volume with anagliptin treatment was also completely inhibited by the NOS inhibitor. GLP-1 augmented eNOS phosphorylation in HCAECs, with the effect completely disappearing after exposure to the protein kinase A (PKA) inhibitor H89. These data suggest that anagliptin treatment enhances insulin-induced capillary recruitment and interstitial insulin concentrations, resulting in improved skeletal muscle glucose Hiroyuki Sato, Naoto Kubota and Tetsuya Kubota contributed equally to this work. Electronic supplementary material The online version of this article

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Po199 a Randomized, Placebo-Controlled, Double-Blind, Phase 3 Trial to Evaluate the Efficacy and Safety of Anagliptin in Patients With Type 2 Diabetes

Cited by 2 publications

References 0 publications

Risk of any hypoglycaemia with newer antihyperglycaemic agents in patients with type 2 diabetes: A systematic review and meta‐analysis

Risk of any hypoglycaemia with newer antihyperglycaemic agents in patients with type 2 diabetes: A systematic review and meta‐analysis

Anagliptin increases insulin-induced skeletal muscle glucose uptake via an NO-dependent mechanism in mice

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