Efficacy and safety of saxagliptin in patients with type 2 diabetes: A systematic review and meta-analysis.

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Term Occurence Count Dictionary
glyburide 1 endocrinologydiseasesdrugs
hypoglycemia 9 endocrinologydiseases
metformin 18 endocrinologydiseasesdrugs
repaglinide 2 endocrinologydiseasesdrugs
sitagliptin 6 endocrinologydiseasesdrugs
acarbose 12 endocrinologydiseasesdrugs
dapagliflozin 7 endocrinologydiseasesdrugs
glipizide 1 endocrinologydiseasesdrugs

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Select Drug Character Offset Drug Term Instance
acarbose 1775 metformin, saxagliptin significantly increased the proportion of patients achieving HbA1c <7% compared with acarbose (RR 2.38, 95% CI 1.17 to 4.83) and uptitrated metformin (RR 1.30, 95% CI 1.04 to 1.63). Saxagliptin
acarbose 2080 control. Saxagliptin significantly decreased the incidences of overall adverse events compared with acarbose (RR 0.71, 95% CI 0.57 to 0.89) and liraglutide (RR 0.41, 95% CI 0.24 to 0.71) when added to metformin.
acarbose 2554 saxagliptin has similar efficacy compared with most oral antidiabetic drugs and may be more effective than acarbose , while having a better safety profile than both acarbose and sulfonylureas.Data AvailabilityAll relevant
acarbose 2611 antidiabetic drugs and may be more effective than acarbose, while having a better safety profile than both acarbose and sulfonylureas.Data AvailabilityAll relevant data are within the paper and its Supporting Information
acarbose 14779 mg/dMET30Yang et al., 2011 [[51]]NCT006613622457054.1275/2957.9159.369.05.1SAXA 5 mg/d PLBMETACBO, acarbose ; DAPA, dapagliflozin; GLMR, glimepiride; GLPZ, glipizide; GLY, glyburide; INS, insulin; LINA, linagliptin;
acarbose 16368 95% CI −0.11 to 0.13; p = 0.89; Fig 2b). Saxagliptin significantly reduced HbA1c in comparison with acarbose (WMD −0.12%, 95% CI −0.22 to −0.02; p = 0.02), but not compared with liraglutide (WMD 0.27%, 95%
acarbose 17331 Similar results was shown when compared with metformin (RR 1.30, 95% CI 1.04 to 1.63; p = 0.02) and acarbose (RR 2.38, 95% CI 1.17 to 4.83; p = 0.02). However, no significant differences were observed in comparisons
acarbose 19086 treatment of saxagliptin. Moreover, saxagliptin significantly reduced overall adverse events compared with acarbose (RR 0.71, 95% CI 0.57 to 0.89; p = 0.03; Fig 4b) and liraglutide (RR 0.41, 95% CI 0.24 to 0.71; p =
acarbose 22101 metformin, saxagliptin significantly increased the proportion of patients achieving HbA1c <7% compared with acarbose and uptitrated metformin. Generally, efficacy on glycemic control of saxagliptin was similar to sitaglitpin
acarbose 22678 and combination therapy. Additionally, saxagliptin group experienced less overall adverse events than acarbose and liraglutide groups when combined with metformin, indicating its favorable safety profile in patients
acarbose 28553 saxagliptin has similar efficacy compared with most oral antidiabetic drugs, while may be more effective than acarbose . Saxagliptin is safe in the treatment of T2D, especially having a better safety profile than acarbose
acarbose 28655 acarbose. Saxagliptin is safe in the treatment of T2D, especially having a better safety profile than acarbose and sulfonylureas.Supporting informationS1 TextPRISMA checklist.(DOC)Click here for additional data
dapagliflozin 1954 CI 1.04 to 1.63). Saxagliptin was similar to other DPP-4 inhibitors but inferior to liraglutide and dapagliflozin on glycemic control. Saxagliptin significantly decreased the incidences of overall adverse events compared
dapagliflozin 14795 et al., 2011 [[51]]NCT006613622457054.1275/2957.9159.369.05.1SAXA 5 mg/d PLBMETACBO, acarbose; DAPA, dapagliflozin ; GLMR, glimepiride; GLPZ, glipizide; GLY, glyburide; INS, insulin; LINA, linagliptin; MET, metformin;
dapagliflozin 16511 −0.02; p = 0.02), but not compared with liraglutide (WMD 0.27%, 95% CI 0.09 to 0.45; p = 0.003) or dapagliflozin (WMD 0.32%, 95% CI 0.11 to 0.53; p = 0.003). Saxagliptin produced similar reduction compared with metformin
dapagliflozin 18359 95% CI 6.18 to 11.93; p < 0.00001), liraglutide (WMD 7.60 mg/dL, 95% CI 1.76 to 13.44; p = 0.01) and dapagliflozin (WMD 18.00 mg/dL, 95% CI 10.10 to 25.90; p < 0.00001). However, no significant differences were observed
dapagliflozin 20196 Saxagliptin was inferior to liraglutide (WMD 5.10 kg, 95% CI 1.66 to 8.54; p = 0.004; S4b Fig) and dapagliflozin (WMD 2.40 kg, 95% CI 1.69 to 3.11; p < 0.00001). However, treatment with saxagliptin was associated
dapagliflozin 21795 monotherapy or add-on therapy to other treatments, including metformin, sulfonylureas, thiazolidinediones, dapagliflozin and insulin. Mean placebo-adjusted HbA1c and FPG levels in saxagliptin add-on therapy were lowered by
dapagliflozin 22270 control of saxagliptin was similar to sitaglitpin and vildagliptin, while inferior to liraglutide and dapagliflozin . More direct comparisons with other active comparators in future trials may provide further evidence
glipizide 14835 [[51]]NCT006613622457054.1275/2957.9159.369.05.1SAXA 5 mg/d PLBMETACBO, acarbose; DAPA, dapagliflozin; GLMR, glimepiride; GLPZ, glipizide ; GLY, glyburide; INS, insulin; LINA, linagliptin; MET, metformin; NA, not available; PLB, placebo; REGL,
glyburide 14851 [[51]]NCT006613622457054.1275/2957.9159.369.05.1SAXA 5 mg/d PLBMETACBO, acarbose; DAPA, dapagliflozin; GLMR, glimepiride; GLPZ, glipizide; GLY, glyburide ; INS, insulin; LINA, linagliptin; MET, metformin; NA, not available; PLB, placebo; REGL, repaglinide;
metformin 1667 of patients achieving HbA1c <7% (RR 1.64, 95% CI 1.53 to 1.75). When combined with submaximal-dose metformin , saxagliptin significantly increased the proportion of patients achieving HbA1c <7% compared with acarbose
metformin 1830 of patients achieving HbA1c <7% compared with acarbose (RR 2.38, 95% CI 1.17 to 4.83) and uptitrated metformin (RR 1.30, 95% CI 1.04 to 1.63). Saxagliptin was similar to other DPP-4 inhibitors but inferior to liraglutide
metformin 2181 acarbose (RR 0.71, 95% CI 0.57 to 0.89) and liraglutide (RR 0.41, 95% CI 0.24 to 0.71) when added to metformin . Weight gain and hypoglycemia with saxagliptin was slightly but significantly higher than placebo and
metformin 3285 in 2015 [[2]]. A diversity of antidiabetic drugs to treat the condition is now available, including metformin , sulfonylureas, thiazolidinediones, α-glucosidase inhibitors, prandial glucose regulators, sodium-glucose
metformin 4447 Study of Diabetes have advocated the use of DPP-4 inhibitors as first-line agent in circumstances where metformin is contraindicated or not tolerated, or within a dual or triple agent regimen [[5]]. Saxagliptin is
metformin 14900 dapagliflozin; GLMR, glimepiride; GLPZ, glipizide; GLY, glyburide; INS, insulin; LINA, linagliptin; MET, metformin ; NA, not available; PLB, placebo; REGL, repaglinide; SAXA, saxagliptin; SITA, sitagliptin; SU, sulfonylurea;
metformin 16244 comparators).Overall, saxagliptin produced similar reduction in HbA1c compared with active comparators when added to metformin (WMD 0.01%, 95% CI −0.11 to 0.13; p = 0.89; Fig 2b). Saxagliptin significantly reduced HbA1c in comparison
metformin 16623 dapagliflozin (WMD 0.32%, 95% CI 0.11 to 0.53; p = 0.003). Saxagliptin produced similar reduction compared with metformin (WMD -0.30%, 95% CI -0.74 to 0.13; p = 0.17), sulfonylureas (WMD 0.14%, 95% CI -0.02 to 0.30; p = 0.08),
metformin 17276 add-on therapy (RR 1.67, 95% CI 1.55 to 1.81; p < 0.00001). Similar results was shown when compared with metformin (RR 1.30, 95% CI 1.04 to 1.63; p = 0.02) and acarbose (RR 2.38, 95% CI 1.17 to 4.83; p = 0.02). However,
metformin 18140 of FPG from baseline (a. saxagliptin vs placebo; b. saxagliptin vs active comparators).When added to metformin , saxagliptin produced a significantly smaller reduction in FPG compared with sulfonylureas (WMD 9.05
metformin 19216 to 0.89; p = 0.03; Fig 4b) and liraglutide (RR 0.41, 95% CI 0.24 to 0.71; p = 0.001) when added to metformin .10.1371/journal.pone.0197321.g004Fig 4Overall adverse events (a. saxagliptin vs placebo; b. saxagliptin
metformin 21749 compared with placebo, both when given as monotherapy or add-on therapy to other treatments, including metformin , sulfonylureas, thiazolidinediones, dapagliflozin and insulin. Mean placebo-adjusted HbA1c and FPG levels
metformin 21993 therapy were lowered by comparable amounts to saxagliptin monotherapy. When combined with submaximal-dose metformin , saxagliptin significantly increased the proportion of patients achieving HbA1c <7% compared with acarbose
metformin 22125 significantly increased the proportion of patients achieving HbA1c <7% compared with acarbose and uptitrated metformin . Generally, efficacy on glycemic control of saxagliptin was similar to sitaglitpin and vildagliptin,
metformin 22729 group experienced less overall adverse events than acarbose and liraglutide groups when combined with metformin , indicating its favorable safety profile in patients with T2D. Compared with sulfonylureas, saxagliptin
metformin 26781 been approved for use in patients with type 2 diabetes, both as monotherapy and in combination with metformin , a sulfonylurea, thiazolidinedione, or insulin, and also in combination with metformin plus insulin.
metformin 26868 combination with metformin, a sulfonylurea, thiazolidinedione, or insulin, and also in combination with metformin plus insulin. However, in some countries like China, it is currently only approved for use as monotherapy
metformin 27007 some countries like China, it is currently only approved for use as monotherapy or in combination with metformin . Our systematic review has demonstrated significant advantages of saxagliptin in achieving glycemic
repaglinide 14950 glyburide; INS, insulin; LINA, linagliptin; MET, metformin; NA, not available; PLB, placebo; REGL, repaglinide ; SAXA, saxagliptin; SITA, sitagliptin; SU, sulfonylurea; TZD, thiazolidinedione; VIDA, vildagliptin.Quality
repaglinide 16856 0.10%, 95% CI -0.01 to 0.20; p = 0.07), vildagliptin (WMD 0.02%, 95% CI -0.15 to 0.19; p = 0.79) and repaglinide (WMD 0.30%, 95% CI -0.18 to 0.78; p = 0.22).A significantly greater proportion of patients treated with
sitagliptin 14988 linagliptin; MET, metformin; NA, not available; PLB, placebo; REGL, repaglinide; SAXA, saxagliptin; SITA, sitagliptin ; SU, sulfonylurea; TZD, thiazolidinedione; VIDA, vildagliptin.Quality of the included studiesA risk
sitagliptin 16738 -0.30%, 95% CI -0.74 to 0.13; p = 0.17), sulfonylureas (WMD 0.14%, 95% CI -0.02 to 0.30; p = 0.08), sitagliptin (WMD 0.10%, 95% CI -0.01 to 0.20; p = 0.07), vildagliptin (WMD 0.02%, 95% CI -0.15 to 0.19; p = 0.79)
sitagliptin 18558 differences were observed when saxagliptin was compared with other active comparators (Fig 3b), including sitagliptin (WMD -0.13 mg/dL, 95% CI -11.44 to 11.18; p = 0.98) and vildaglitpin (WMD 5.52 mg/dL, 95% CI -0.78 to
sitagliptin 20921 significantly between saxagliptin and placebo (RR 1.02, 95% CI 0.92 to 1.13; p = 0.66; S5c Fig), Compared with sitagliptin , saxagliptin could significantly reduced the risk of arthralgia (RR 0.20, 95% CI 0.04 to 0.90; p = 0.04;
sitagliptin 25825 signal for increased risk of arthralgia in the saxagliptin treatment, and a possible better effect than sitagliptin . Furthermore, there was no increased risk of pancreatitis and infections as supported by our studies,
sitagliptin 27983 Secondly, two trials included in the meta-analysis, which comparing saxagliptin with vildagliptin, sitagliptin and (or) liraglutide, were found to have possible high risk of performance and detection bias. This
Select Disease Character Offset Disease Term Instance
hypoglycemia 2208 0.57 to 0.89) and liraglutide (RR 0.41, 95% CI 0.24 to 0.71) when added to metformin. Weight gain and hypoglycemia with saxagliptin was slightly but significantly higher than placebo and lower than sulfonylureas. Saxagliptin
hypoglycemia 7270 fasting plasma glucose (FPG) concentration, overall and serious adverse events, body weight, confirmed hypoglycemia , heart failure, pancreatitis, arthralgia, and other adverse events [hypertension, urinary tract infection,
hypoglycemia 19455 comparators).HypoglycemiaCompared with placebo, saxaglitpin significantly but slightly increased the incidences of hypoglycemia (RR 1.13, 95% CI 1.05 to 1.21; p = 0.0009; Fig 5a). Compared with sulfonylureas, saxaglitpin significantly
hypoglycemia 19595 1.21; p = 0.0009; Fig 5a). Compared with sulfonylureas, saxaglitpin significantly reduced the risk of hypoglycemia by 95% (RR 0.05, 95% CI 0.01 to 0.23; p = 0.0002; Fig 5b). No significant differences were observed
hypoglycemia 22878 profile in patients with T2D. Compared with sulfonylureas, saxagliptin had a significant better effect on hypoglycemia and body weight gain. Treatment of saxagliptin was shown to be with a minimal increase of hypoglycemia,
hypoglycemia 22981 hypoglycemia and body weight gain. Treatment of saxagliptin was shown to be with a minimal increase of hypoglycemia , which mainly depending on the result from the included Saxagliptin Assessment of Vascular Outcomes
hypoglycemia 23381 therapies at the doctor’s discretion. A post-hoc analysis [[52]] of SAVOR-TIMI 53 trial found that hypoglycemia rates (any or major) were increased with saxagliptin in patients taking sulfonylureas, not in those
hypoglycemia 23612 pooled analysis also found that saxagliptin was not associated with increased reported or confirmed hypoglycemia when use of sulfonylurea was excluded [[53]]. Thus, lower doses of sulfonylureas might be required to
hypoglycemia 24049 manner. Consequently, it may still be an appropriate agent for patients with relatively higher risk of hypoglycemia .The potential safety issue of heart failure risk that arose from SAVOR-TIMI 53 and the Examination of

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