Glucagon-like peptide-1 receptor agonists compared with basal insulins for the treatment of type 2 diabetes mellitus: a systematic review and meta-analysis

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Term Occurence Count Dictionary
Exenatide 11 endocrinologydiseasesdrugs
diabetes mellitus 2 endocrinologydiseases
hypoglycemia 4 endocrinologydiseases
metformin 2 endocrinologydiseasesdrugs
Albiglutide 2 endocrinologydiseasesdrugs
Insulin 3 endocrinologydiseasesdrugs
Liraglutide 5 endocrinologydiseasesdrugs
dulaglutide 24 endocrinologydiseasesdrugs
type 2 diabetes mellitus 2 endocrinologydiseases

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Select Drug Character Offset Drug Term Instance
Albiglutide 16891 (82%‐83%), MET + TZD (17%‐18%)Degludec54.9 (9.7)52.0627.0 (5.3)8.3 (1.0)6787.4 (19.2)31.2 (5.3) Albiglutide 30 mg once weekly vs insulin glargineHARMONY4 (Weissman 2014)156Albiglutide55.8 (9.3)43.3698.9 (6.5)8.3
Albiglutide 16967 (1.0)6787.4 (19.2)31.2 (5.3)Albiglutide 30 mg once weekly vs insulin glargineHARMONY4 (Weissman 2014)156 Albiglutide 55.8 (9.3)43.3698.9 (6.5)8.3 (0.9)6795.1 (19.7)33.2 (5.6)MET + SU (82%)Glargine54.7 (9.8)45.2668.4 (5.7)8.4
Exenatide 14746 HbA1c (SD), %Mean HbA1c (mmol/mol)Mean bodyweight (SD), kgMean BMI (SD), kg/m2Background therapy, % Exenatide 10 µg twice daily vs insulin glargineBunck 200952Exenatide158.4 (−)36.1–5.7 (−)7.6 (−)6090.6
Exenatide 14806 kgMean BMI (SD), kg/m2Background therapy, %Exenatide 10 µg twice daily vs insulin glargineBunck 200952 Exenatide 158.4 (−)36.1–5.7 (−)7.6 (−)6090.6 (−)30.9 (−)MET (100%)Glargine58.3 (−)33.3–4.0 (−)7.4
Exenatide 14969 (−)MET (100%)Glargine58.3 (−)33.3–4.0 (−)7.4 (−)5792.4 (−)30.1 (−)HEELA (Davies 2009)26 Exenatide 56.8 (10.2)29.7–9.0 (4.6)8.7 (0.7)72101.4 (19.8)34.6 (5.7)Double/triple therapy MET ± SU ± TZDGlargine56.2
Exenatide 15154 therapy MET ± SU ± TZDGlargine56.2 (7.9)33.6–8.4 (4.4)8.5 (0.7)6997.6 (16.4)33.7 (4.9)Heine 200526 Exenatide 59.8 (8.8)45.0809.9 (6.0)8.2 (1.0)6687.5 (16.9)31.4 (4.4)MET + SU (100%)Glargine58.0 (9.5)43.4819.2 (5.7)8.3
Exenatide 15313 (16.9)31.4 (4.4)MET + SU (100%)Glargine58.0 (9.5)43.4819.2 (5.7)8.3 (1.0)6788.3 (17.9)31.3 (4.6)Gurkan 201426 Exenatide 52.2 (7.3)70.0–6.9 (3.3)8.0 (0.8)6494.3 (11.8)35.9 (3.7)MET (100%)Glargine53.1 (7.0)58.8–7.6 (4.3)8.1
Exenatide 15470 (11.8)35.9 (3.7)MET (100%)Glargine53.1 (7.0)58.8–7.6 (4.3)8.1 (0.8)6590.5 (14.3)33.2 (4.5)Barnett 200732 Exenatide 54.5 (−)51.5–6.6 (−)8.9 (−)7485.6 (−)31.3 (−)MET (55%‐56%) or SU (44%‐46%)Glargine55.3
Exenatide 15634 (−)MET (55%‐56%) or SU (44%‐46%)Glargine55.3 (−)54.3–8.3 (−)9.0 (−)7584.0 (−)30.9 (−) Exenatide 2 mg once weekly vs insulin glargineDURATION‐3 (Diamant 2010, 2014)156Exenatide58.0 (10.0)48.0828.0
Exenatide 15716 (−)7584.0 (−)30.9 (−)Exenatide 2 mg once weekly vs insulin glargineDURATION‐3 (Diamant 2010, 2014)156 Exenatide 58.0 (10.0)48.0828.0 (6.0)8.3 (1.1)6791.2 (18.6)32.3 (5.4)MET (70%)Glargine58.0 (9.0)45.0857.8 (6.0)8.3
Exenatide 15871 (18.6)32.3 (5.4)MET (70%)Glargine58.0 (9.0)45.0857.8 (6.0)8.3 (1.0)6790.6 (16.4)32.3 (4.8)Inagaki 201262 Exenatide 57.1 (10.4)34.0028.9 (6.1)8.5 (0.8)6970.0 (13.3)26.1 (4.03)MET (67%), BG + TZD (33%)Glargine56.4 (11.2)30.2029.2
Exenatide 16030 (13.3)26.1 (4.03)MET (67%), BG + TZD (33%)Glargine56.4 (11.2)30.2029.2 (6.0)8.5 (0.8)6971.0 (13.9)26.2 (3.8) Exenatide 2 mg once weekly vs insulin detemirDavies 201330Exenatide59.0 (10.0)36.0948.0 (6.0)8.4 (0.9)6896.7 (17.0)33.7
Exenatide 16088 (11.2)30.2029.2 (6.0)8.5 (0.8)6971.0 (13.9)26.2 (3.8)Exenatide 2 mg once weekly vs insulin detemirDavies 201330 Exenatide 59.0 (10.0)36.0948.0 (6.0)8.4 (0.9)6896.7 (17.0)33.7 (4.7)MET (100%) + SU (70%‐72%)Detemir58.0 (10.0)31.0977.0
Insulin 18073 majority of participants received exenatide 10 µg twice daily.2Trial conducted in a Japanese population.3 Insulin glargine arm: MET = 99.6%, SU = 67.5%, SUs taken by 60% of participants at baseline and reduced to 49%
Insulin 18456 investigators discretion.4Dulaglutide arm: SU monotherapy (19%), MET monotherapy (35%), SU + MET (46%). Insulin glargine arm: SU monotherapy (18%), MET monotherapy (37%), SU + MET (45%).Mean patient age in the included
Insulin 37963 informationAppendix S1. Medline search strategy (OVID SP).Figure S1. Risk of bias of included studies.Table S1. Insulin titration algorithm and FPG targets.Table S2.HbA1c (%) change from baseline and target achievement at
Liraglutide 16247 (17.0)33.7 (4.7)MET (100%) + SU (70%‐72%)Detemir58.0 (10.0)31.0977.0 (5.0)8.4 (0.9)6897.9 (15.8)33.7 (4.7) Liraglutide 1.8 mg once daily vs insulin glargineEAGLE (D'Alessio 2015)24Liraglutide57.4 (8.9)44.0––9.1 (1.1)7690.1
Liraglutide 16320 (0.9)6897.9 (15.8)33.7 (4.7)Liraglutide 1.8 mg once daily vs insulin glargineEAGLE (D'Alessio 2015)24 Liraglutide 57.4 (8.9)44.0––9.1 (1.1)7690.1 (16.7)31.8 (4.1)MET + SU3Glargine57.1 (8.8)47.3––9.0 (1.0)7590.8
Liraglutide 16485 (4.1)MET + SU3Glargine57.1 (8.8)47.3––9.0 (1.0)7590.8 (16.6)32.0 (4.2)LEAD‐5 (Russell‐Jones 2009)26 Liraglutide 57.6 (9.5)43.0–9.2 (5.8)8.3 (0.9)6785.5 (19.4)30.4 (5.3)MET + SU (94%‐95%)Glargine57.5 (10.5)40.0–9.7
Liraglutide 16641 (19.4)30.4 (5.3)MET + SU (94%‐95%)Glargine57.5 (10.5)40.0–9.7 (6.4)8.2 (0.9)6685.0 (17.9)30.3 (5.3) Liraglutide 1.8 mg once daily vs insulin degludecDUAL‐I (Gough 2014, 2015)52Liraglutide55.0 (10.2)50.0627.2 (6.1)8.3
Liraglutide 16719 (0.9)6685.0 (17.9)30.3 (5.3)Liraglutide 1.8 mg once daily vs insulin degludecDUAL‐I (Gough 2014, 2015)52 Liraglutide 55.0 (10.2)50.0627.2 (6.1)8.3 (0.9)6787.4 (18.0)31.3 (4.8)MET (82%‐83%), MET + TZD (17%‐18%)Degludec54.9
dulaglutide 2130 and 11 were meta‐analysed. The once‐weekly GLP‐1 RAs, exenatide long acting release (LAR) and dulaglutide , led to greater, statistically significant mean HbA1c reductions vs basal insulins (exenatide: −0.31%
dulaglutide 2290 HbA1c reductions vs basal insulins (exenatide: −0.31% [95% confidence interval −0.42, −0.19], dulaglutide : −0.39% [−0.49, −0.29]) whilst once‐daily liraglutide and twice‐daily exenatide did not (liraglutide:
dulaglutide 2919 weight reduction is seen with all GLP‐1 RA’s, only the once‐weekly agents, exenatide LAR and dulaglutide , demonstrate significant HbA1c reductions when compared to basal insulins.SinghS, WrightEEJr., KwanAYM,
dulaglutide 4318 options and in 2014, two new once‐weekly GLP‐1 RAs received marketing authorization: albiglutide and dulaglutide .5, 6, 7, 8The clinical effectiveness and safety of GLP‐1 RAs compared to each other and to oral antihyperglycemic
dulaglutide 4942 14, 15, 16 they all have limitations to consider. Wang et al. 15 do not include the two new agents ( dulaglutide and albiglutide) and, although Karagiannis et al. 10 do include the new treatments, their analysis is
dulaglutide 7412 (long acting release [LAR]), lixisenatide 20 µg once daily, albiglutide 30 or 50 mg once weekly, and dulaglutide 0.75 or 1.5 mg once weekly plus at least one OAD; (3) comparator arm of basal insulin (ie, insulin detemir,
dulaglutide 13539 of exenatide 10 µg or 2 mg, liraglutide 1.8 mg, albiglutide 30 mg (uptitrated to 50 mg as needed), dulaglutide 0.75 or 1.5 mg or lixisenatide 20 µg with insulin detemir, glargine or degludec. Eligible studies reporting
dulaglutide 13929 baseline, 9 reported hypoglycemic episodes and 11 reported severe hypoglycemic episodes. As data for the dulaglutide 1.5 mg dose, albiglutide 30 and 50 mg doses and lixisentatide 20 µg were identified in only 1 study
dulaglutide 20410 vs insulin glargine29, 33; 2 trials of liraglutide 1.8 mg vs insulin glargine36, 39; and 2 trials of dulaglutide 0.75 mg vs insulin glargine.21, 28 Four studies could not be included in the pair‐wise meta‐analysis
dulaglutide 20963 addition, although 2 studies were available for a pair‐wise meta‐analysis of the 0.75 mg dose of dulaglutide 21, 28 to be performed, only 1 study reported both doses of dulaglutide (0.75 and 1.5 mg).21 In the absence
dulaglutide 21034 meta‐analysis of the 0.75 mg dose of dulaglutide21, 28 to be performed, only 1 study reported both doses of dulaglutide (0.75 and 1.5 mg).21 In the absence of another study with the 1.5 mg dose, a pair‐wise analysis for
dulaglutide 22272 and −0.39% (95% CI, −0.49, −0.29; I2 = 88.6%) (−0.43 mmol/L [95% CI, −5.4, −3.2]) with dulaglutide 0.75 mg (Figure 2A).The RCT conducted by Bunck et al.20 included 5 different doses of exenatide: 10
dulaglutide 23766 −4.22; I2 = 89.1%) with liraglutide 1.8 mg, and −1.98 kg (95% CI, −2.32, −1.64, I2 = 91%) with dulaglutide 0.75 mg. Removing the RCT conducted by Bunck et al.20 minimally changed the overall effect estimate
dulaglutide 25540 and 95.0% in the insulin glargine arm were receiving SU. ‡‡‡The majority of the patients in the dulaglutide group (65.0%) and insulin glargine group (63.0%) received SU at baseline. In the dulaglutide and insulin
dulaglutide 25633 in the dulaglutide group (65.0%) and insulin glargine group (63.0%) received SU at baseline. In the dulaglutide and insulin glargine groups, 13/117 (11.1%) and 11/114 (9.6%) patients, respectively, decreased their
dulaglutide 26946 statistically significant reductions in HbA1c with once‐weekly exenatide 2 mg LAR and once‐weekly dulaglutide 0.75 mg, compared to insulin glargine at 6 months, a reduction in HbA1c of 0.3% (3.3 mmol/L) and 0.4%
dulaglutide 27815 vs insulin glargine29, 33; 2 trials of liraglutide 1.8 mg vs insulin glargine36, 39; and 2 trials of dulaglutide 0.75 mg vs insulin glargine.21, 28 Although it was not possible to incorporate data for dulaglutide
dulaglutide 27915 dulaglutide 0.75 mg vs insulin glargine.21, 28 Although it was not possible to incorporate data for dulaglutide 1.5 mg, lixisenatide or albiglutide into the analyses, as only 1 study for each met the inclusion criteria
dulaglutide 28201 be considered that the 3‐armed trial identified by the systematic review that included the 1.5 mg dulaglutide dose (vs dulaglutide 0.75 mg and insulin glargine) indicated that the higher dose led to a greater reduction
dulaglutide 28222 the 3‐armed trial identified by the systematic review that included the 1.5 mg dulaglutide dose (vs dulaglutide 0.75 mg and insulin glargine) indicated that the higher dose led to a greater reduction in HbA1c and
dulaglutide 28363 indicated that the higher dose led to a greater reduction in HbA1c and bodyweight compared to both dulaglutide 0.75 mg and insulin glargine (Figure 2).21 With lixisenatide, a weight reduction was observed compared
dulaglutide 29374 kg (95% CI −3.20 to −2.49) for exenatide 2 mg LAR, and −1.98 kg (95% CI −2.32, −1.64) for dulaglutide 0.75 mg.The results of the 2 pairwise meta‐analyses indicated that there is a lower risk of hypoglycaemia
dulaglutide 34373 were not included in the meta‐analysis, notably albiglutide 30 mg (uptitrated to 50 mg as needed), dulaglutide 1.5 mg (where only one study comparing it to basal insulin at this dose was available) and lixisenatide
dulaglutide 37252 studies.In conclusion, the current analysis indicates that once‐weekly GLP‐1 Ras, exenatide LAR and dulaglutide , demonstrate a greater reduction in HbA1c compared to basal insulin after 26 weeks of treatment. Once‐
metformin 3926 diabetes treatment algorithms include GLP‐1 RAs as a therapy option after initial treatment with metformin (MET).2, 3, 4 Since the introduction of exenatide twice daily (BID) for the treatment of type 2 diabetes
metformin 17886 (16.3)31.7 (4.5)Abbreviations: BG, biguanine; BMI, body mass index; HbA1c, glycated hemoglobin; MET, metformin ; SD, standard deviation; SU, sulfonylurea; TZD, thiazolidinedione.1The majority of participants received
Select Disease Character Offset Disease Term Instance
diabetes mellitus 140 MetabolismGlucagon‐like peptide‐1 receptor agonists compared with basal insulins for the treatment of type 2 diabetes mellitus : a systematic review and meta‐analysisAlternative Title: SINGHet al.Alternative Title: SINGHet al.Sonal
diabetes mellitus 3194 Glucagon‐like peptide‐1 receptor agonists compared with basal insulins for the treatment of type 2 diabetes mellitus : A systematic review and meta‐analysis, Diabetes Obes Metab, 2017;19(2):228–238.27717130INTRODUCTION1Several
hypoglycemia 8724 characteristics, treatment arm details, efficacy (glycated hemoglobin [HbA1c], weight) and safety outcomes ( hypoglycemia , gastrointestinal adverse events).Endpoints at week 26 (±10 weeks) were extracted and reported. If
hypoglycemia 24649 presented in Figure 3B.Figure 3Effect of GLP‐1 RA compared to basal insulin at 26 weeks (±10 weeks) on hypoglycemia , odds ratio (A), and proportion (%) (B). Abbreviations: CI, confidence interval; GLP‐1 RA, glucagon‐like
hypoglycemia 25796 11/114 (9.6%) patients, respectively, decreased their concomitant SU dose from baseline as a result of hypoglycemia . §Figure includes only insulin glargine trials to highlight the differences in proportions of patients
hypoglycemia 36177 direct and indirect data by network meta‐analysis may be warranted.The meta‐analysis conducted for hypoglycemia should be interpreted with caution because of high heterogeneity in defining hypoglycaemic events, an
type 2 diabetes mellitus 133 MetabolismGlucagon‐like peptide‐1 receptor agonists compared with basal insulins for the treatment of type 2 diabetes mellitus : a systematic review and meta‐analysisAlternative Title: SINGHet al.Alternative Title: SINGHet al.Sonal
type 2 diabetes mellitus 3187 JunejaR. Glucagon‐like peptide‐1 receptor agonists compared with basal insulins for the treatment of type 2 diabetes mellitus : A systematic review and meta‐analysis, Diabetes Obes Metab, 2017;19(2):228–238.27717130INTRODUCTION1Several

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