The Use of Exenatide in Managing Markers of Cardiovascular Risk in Patients with Type 2 Diabetes: A Systematic Review

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Term Occurence Count Dictionary
obesity 1 endocrinologydiseases
pioglitazone 3 endocrinologydiseasesdrugs
rosiglitazone 1 endocrinologydiseasesdrugs
Exenatide 36 endocrinologydiseasesdrugs
Glimepiride 3 endocrinologydiseasesdrugs
Insulin 2 endocrinologydiseasesdrugs
metformin 23 endocrinologydiseasesdrugs

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Select Drug Character Offset Drug Term Instance
Exenatide 83 Title: International Journal of Environmental Research and Public HealthThe Use of Exenatide in Managing Markers of Cardiovascular Risk in Patients with Type 2 Diabetes: A Systematic ReviewOmorogieva
Exenatide 6869 production, delaying gastric emptying, and reducing appetite and food intake by increasing satiety [[10]]. Exenatide is a 39-amino acid peptide and is an incretin mimetic, which was the first of the new incretin mimetic
Exenatide 7073 mimetic class of antihyperglycaemic agents to be marketed in the US and European Union [[9],[11]]. Exenatide is a short acting agent, which can be administered subcutaneously twice daily (exenatide BID) although
Exenatide 13271 duration of diabetes of the patients in the studies ranged from 1 ± 2 to 12 ± 7 years (Mean ± SD). 3.1. Exenatide Twice Daily versus Placebo Exenatide twice daily was compared to placebo in seven of the 11 studies
Exenatide 13308 studies ranged from 1 ± 2 to 12 ± 7 years (Mean ± SD). 3.1. Exenatide Twice Daily versus Placebo Exenatide twice daily was compared to placebo in seven of the 11 studies [[19],[20],[21],[22],[23],[24],[25]]
Exenatide 14870 treatment groups, while systolic blood pressure remained relatively unchanged from baseline values.3.2. Exenatide Twice Daily versus Other ControlsWhile one of the remaining 4 studies had placebo + lifestyle modification
Exenatide 22126 RateOutcomes/Body WeightGastaldelli et al. [[19]]4 countries (Multi-centre)24 weeksRandomised Controlled Study79 Exenatide (10 μg) 59 ± 22 ± 3 (exenatide 5 μg)–Exenatide twice daily versus placeboCompared to placebo,
Exenatide 22179 (Multi-centre)24 weeksRandomised Controlled Study79Exenatide (10 μg) 59 ± 22 ± 3 (exenatide 5 μg)– Exenatide twice daily versus placeboCompared to placebo, 24 weeks of daily high or low dose exenatide treatment
Exenatide 22461 0.05)––There were no differences in weight changes between the two exenatide and placebo groups Exenatide (5 μg) 57 ± 22 ± 3 (exenatide 10 μg)Placebo 54 ± 21 ± 2 (placebo)Derosa et al. [[20]]Italy (Multi-centre)4
Exenatide 22755 (given for 8 months before randomly assigning patients), diet and exercise advise (commenced at baseline) Exenatide twice daily versus placeboExenatide + metformin were better than placebo + metformin in decreasing HbA1c
Exenatide 22791 assigning patients), diet and exercise advise (commenced at baseline)Exenatide twice daily versus placebo Exenatide + metformin were better than placebo + metformin in decreasing HbA1c at 12 months (p < 0.05). Similar
Exenatide 23494 al. [[21]]5 countries (Multi-centre)30 weeksRandomised Controlled Study25959 ± 9 (exenatide)12 ± 7 ( Exenatide )Insulin glargine, metformin, pioglitazone Treatments given to participants for at least 3 months before
Exenatide 23662 to participants for at least 3 months before study commenced and continued throughout study period. Exenatide twice daily versus placeboExenatide participants had greater HbA1C reductions compared with placebo
Exenatide 23698 months before study commenced and continued throughout study period.Exenatide twice daily versus placebo Exenatide participants had greater HbA1C reductions compared with placebo participants at end point (p < 0.001)––Exenatide
Exenatide 23815 participants had greater HbA1C reductions compared with placebo participants at end point (p < 0.001)–– Exenatide participants lost more weight (p < 0.05)59 ± 10 (placebo)12 ± 7 (placebo)Buse et al. [[22]]5 countries
Exenatide 24213 to participants for at least 3 months before study commenced and continued throughout study period. Exenatide twice daily versus placeboHbA1c level decreased by 1.74% with exenatide and 1.04% with placebo (p <
Exenatide 24859 (placebo)Gill et al. [[23]]Canada and Netherlands (Multi-centre)12 weeksRandomised Controlled Study54 Exenatide 57 ± 117 ± 4 (exenatide)Metformin (given for 30 days and continued during study), thiazolidinedione
Exenatide 25075 (given for 120 days and continued during study), metformin + thiazolidinedione (continued during study). Exenatide twice daily versus placeboHbA1c reduction was not significantly different between the 2 groups (p =
Exenatide 25272 groups (p = 0.26)–Differences in heart rate between the 2 groups was not significant (p = 0.16). Exenatide therapy showed trends towards lower systolic BP, but similar diastolic BP between the groups.There were
Exenatide 25765 sulfonylurea and thiazolidine derivative. Treatments given to participants for 90 days before screening. Exenatide twice daily versus placeboThe changes in HbA1c levels were significantly greater (p < 0.001) in both
Exenatide 26419 ± 6.5 (placebo)Liutkus et al. [[25]]5 countries (Multi-centre)26 weeksRandomised Controlled Study165 Exenatide (55 ± 8)Exenatide (6.3 ± 4.2)Thiazolidinedione (given for 120 days before study), metformin + thiazolidinedione
Exenatide 26438 (placebo)Liutkus et al. [[25]]5 countries (Multi-centre)26 weeksRandomised Controlled Study165Exenatide (55 ± 8) Exenatide (6.3 ± 4.2)Thiazolidinedione (given for 120 days before study), metformin + thiazolidinedione (given
Exenatide 26657 least 90 days before study). Participants continued their usual treatment for the duration of study. Exenatide twice daily versus placeboExenatide showed superiority with respect to change in HbA1c (p < 0.001) and
Exenatide 26693 Participants continued their usual treatment for the duration of study.Exenatide twice daily versus placebo Exenatide showed superiority with respect to change in HbA1c (p < 0.001) and fasting serum glucose (p = 0.009)
Exenatide 27265 9)Placebo (6.4 ± 4.6)Apovian et al. [[26]]USA (11 centres)24 weeksRandomised Controlled Study19454.8 ± 9.5 Exenatide (5.7 ± 5.5)Metformin or sulfonylurea or both. Participants treated for at least 6 weeks before study
Exenatide 27404 sulfonylurea or both. Participants treated for at least 6 weeks before study and continued during study. Exenatide twice daily + lifestyle modification programme placebo + lifestyle modification programmeSignificantly
Exenatide 27676 modification had HbA1c ≤ 6.5% at end point compared with placebo + lifestyle modification (p = 0.001)– Exenatide + lifestyle modification was associated with significant decrease in systolic and diastolic BP at 24
Exenatide 27876 diastolic BP at 24 weeks from baseline compared with placebo + lifestyle modification (p < 0.001; p = 0.04 ) Exenatide + lifestyle modification had significantly more weight loss compared with placebo + lifestyle modification
Exenatide 28104 0.01)Placebo (5.3 ± 5.1)Simo et al. [[27]]14 countries (Multi-centre)4½ yearsRandomised Controlled Study Exenatide (n = 511)18–855.8 ± 4.8 (exenatide)Metformin (participants treated before study and continued treatment
Exenatide 28234 ± 4.8 (exenatide)Metformin (participants treated before study and continued treatment during study) Exenatide twice daily versus glimepirideSymptomatic hypoglycaemia was reported during 1 year of study treatment
Exenatide 28950 4.3 (glimepiride)Gallwitz et al. [[28]]14 countries (128 centres)4½ yearsRandomised Controlled Study Exenatide = 49018–855.8 ± 4.8 (exenatide)Metformin (participants treated before study and continued treatment
Exenatide 29076 ± 4.8 (exenatide)Metformin (participants treated before study and continued treatment during study) Exenatide twice daily versus glimepiride44% in exe natide group and 31% in glimepiride gp achieved HbA1c < 7%
Exenatide 29803 (glimepiride)Gallwitz et al. [[29]]Germany (Multi-centre)26 weeksRandomised Controlled Study35457 ± 10 ( Exenatide )5 ± 4 (Exenatide)Metformin (participants treated before study and continued treatment during study)Exenatide
Exenatide 29821 et al. [[29]]Germany (Multi-centre)26 weeksRandomised Controlled Study35457 ± 10 (Exenatide)5 ± 4 ( Exenatide )Metformin (participants treated before study and continued treatment during study)Exenatide twice daily
Exenatide 29913 (Exenatide)5 ± 4 (Exenatide)Metformin (participants treated before study and continued treatment during study) Exenatide twice daily versus premixed insulin aspart (PIA)HbA1c targets < 7% and <6.5% (exenatide noninferior
Exenatide 30132 Hypoglcaemic epiosdes with blood glucose ≤ 3.0 mmols/L were less frequent with exenatide BID–– Exenatide twice daily (weight loss = 4.1 ± 0.22 kg)PIA(weight gain = 1.0 ± 0.22 kg) SEM (p < 0.001)57 ± 9.9
Glimepiride 15259 lifestyle modification with metformin and/or sulfonylurea as background treatment [[25]]; exenatide versus Glimepiride with metformin as background treatment [[27],[28]]; exenatide versus premixd insulin aspart with metformin
Glimepiride 28821 were significantly in favor of exenatide for body weight (p < 0.0001), waist circumference (p < 0.001). Glimepiride (n = 508)5.5 ± 4.3 (glimepiride)Gallwitz et al. [[28]]14 countries (128 centres)4½ yearsRandomised
Glimepiride 29670 group.Significant decrease (p < 0.0001) in body weight in exenatide group compared with glimepiride group Glimepiride = 4875.5 ± 4.3 (glimepiride)Gallwitz et al. [[29]]Germany (Multi-centre)26 weeksRandomised Controlled
Insulin 23504 countries (Multi-centre)30 weeksRandomised Controlled Study25959 ± 9 (exenatide)12 ± 7 (Exenatide) Insulin glargine, metformin, pioglitazone Treatments given to participants for at least 3 months before study
Insulin 24020 countries (59 centres)30 weeksRandomised Controlled Study m25959 ± 9 (exenatide)12 ± 7 (exenatide) Insulin glargine with or without metformin or pioglitazone (or both agents). Treatments given to participants
metformin 2935 more effective in reducing body weight in patients with type 2 diabetes when used in combination with metformin than when used alone or in combination with thiazolidinedione. The findings of this review would suggest
metformin 4112 nature of type 2 diabetes despite the use of diet, physical activity and current therapies, such as metformin , sulfonylurea and insulin, may explain why therapeutic requirements tend to increase with time [[1],[5]].
metformin 5336 lowering therapy in adults with type 2 diabetes. According to the guideline, if a triple therapy (such as metformin , a Dipeptidyl peptidase-4-inhibitor and sulfonylurea) is not effective, not tolerated or contraindicated,
metformin 5513 effective, not tolerated or contraindicated, then, it will be useful to consider combination therapy with metformin , a sulfonylurea and a Glucagon-like peptide-1 (GLP-1) mimetic for adults with type 2 diabetes. To qualify
metformin 12723 intervention treatments except the study by Gastaldelli et al. [[19]]. The background treatments included metformin and/or insulin glargine, pioglitazone, diet and exercise, and thiazolidinedione. Other background treatments
metformin 12903 thiazolidinedione. Other background treatments were sulfonylurea and/or biguanide, thiazolidinedione and/or metformin . The background treatments were treatments taken by participants before the commencement of the study
metformin 13470 11 studies [[19],[20],[21],[22],[23],[24],[25]] (Table 1).Participants in the exenatide groups with metformin as one of the background treatments showed statistically significant decrease in body weight in five
metformin 15180 interventions included; exenatide + lifestyle modification versus placebo + lifestyle modification with metformin and/or sulfonylurea as background treatment [[25]]; exenatide versus Glimepiride with metformin as background
metformin 15276 with metformin and/or sulfonylurea as background treatment [[25]]; exenatide versus Glimepiride with metformin as background treatment [[27],[28]]; exenatide versus premixd insulin aspart with metformin as background
metformin 15368 Glimepiride with metformin as background treatment [[27],[28]]; exenatide versus premixd insulin aspart with metformin as background treatment [[29]].In all the 4 studies [[26],[27],[28],[29]] (Table 1), there were significantly
metformin 19154 group. While one of these studies had no background treatment [[19]], the other had thiazolidinedione, metformin plus thiazolidinedione [[25]]. Therefore, it would appear that exenatide is more effective in reducing
metformin 19342 more effective in reducing body weight in patients with type 2 diabetes when used in combination with metformin than when used alone or in combination with thiazolidinedione. Increases in body weight and body mass
metformin 21706 by reducing body weight, HbA1c and blood pressure. In particular, the combination of exenatide with metformin was more effective in reducing body weight than using exenatide alone.ijerph-13-00941-t001_Table 1Table
metformin 22803 patients), diet and exercise advise (commenced at baseline)Exenatide twice daily versus placeboExenatide + metformin were better than placebo + metformin in decreasing HbA1c at 12 months (p < 0.05). Similar trend was
metformin 22840 (commenced at baseline)Exenatide twice daily versus placeboExenatide + metformin were better than placebo + metformin in decreasing HbA1c at 12 months (p < 0.05). Similar trend was recorded for fasting blood glucose.No
metformin 23072 profile were observed in either of the 2 groupsSystolic and diastolic BP were not changed by placebo + metformin , but decreased by treatment with exenatide + metformin at 12 months compared with point of randomisation
metformin 23127 and diastolic BP were not changed by placebo + metformin, but decreased by treatment with exenatide + metformin at 12 months compared with point of randomisation (p < 0.05)Body mass and BMI obtained after 9 months
metformin 23268 point of randomisation (p < 0.05)Body mass and BMI obtained after 9 months and 12 months of exenatide + metformin were lower than the ones obtained for placebo + metformin group (p < 0.05 and p < 0.01 respectively)Rosenstock
metformin 23326 after 9 months and 12 months of exenatide + metformin were lower than the ones obtained for placebo + metformin group (p < 0.05 and p < 0.01 respectively)Rosenstock et al. [[21]]5 countries (Multi-centre)30 weeksRandomised
metformin 23522 (Multi-centre)30 weeksRandomised Controlled Study25959 ± 9 (exenatide)12 ± 7 (Exenatide)Insulin glargine, metformin , pioglitazone Treatments given to participants for at least 3 months before study commenced and continued
metformin 24053 weeksRandomised Controlled Study m25959 ± 9 (exenatide)12 ± 7 (exenatide)Insulin glargine with or without metformin or pioglitazone (or both agents). Treatments given to participants for at least 3 months before study
metformin 25020 days and continued during study), thiazolidinedione (given for 120 days and continued during study), metformin + thiazolidinedione (continued during study).Exenatide twice daily versus placeboHbA1c reduction was
metformin 26513 Study165Exenatide (55 ± 8)Exenatide (6.3 ± 4.2)Thiazolidinedione (given for 120 days before study), metformin + thiazolidinedione (given for at least 90 days before study). Participants continued their usual treatment
pioglitazone 12758 by Gastaldelli et al. [[19]]. The background treatments included metformin and/or insulin glargine, pioglitazone , diet and exercise, and thiazolidinedione. Other background treatments were sulfonylurea and/or biguanide,
pioglitazone 23533 weeksRandomised Controlled Study25959 ± 9 (exenatide)12 ± 7 (Exenatide)Insulin glargine, metformin, pioglitazone Treatments given to participants for at least 3 months before study commenced and continued throughout
pioglitazone 24066 Controlled Study m25959 ± 9 (exenatide)12 ± 7 (exenatide)Insulin glargine with or without metformin or pioglitazone (or both agents). Treatments given to participants for at least 3 months before study commenced and
rosiglitazone 19740 pressure [[12],[32]]. In addition, exenatide twice daily is superior to insulin, sulfonylureas and rosiglitazone in decreasing body weight [[9]].Another mechanism of the potential action of exenatide on cardiovascular
Select Disease Character Offset Disease Term Instance
obesity 5872 therapy would have significant occupational implications, or weight loss would benefit other significant obesity related co-morbidities. Similar approach in the form of algorithm for the initiation and adjustment

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