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Review
. 2011 Oct 5;2011(10):CD006423.
doi: 10.1002/14651858.CD006423.pub2.

Glucagon-like peptide analogues for type 2 diabetes mellitus

Deepson S Shyangdan  1 , Pamela Royle, Christine Clar, Pawana Sharma, Norman Waugh, Alisa Snaith
Affiliations
Review

Glucagon-like peptide analogues for type 2 diabetes mellitus

Deepson S Shyangdan et al. Cochrane Database Syst Rev. .

Abstract

Background: Glucagon-like peptide analogues are a new class of drugs used in the treatment of type 2 diabetes that mimic the endogenous hormone glucagon-like peptide 1 (GLP-1). GLP-1 is an incretin, a gastrointestinal hormone that is released into the circulation in response to ingested nutrients. GLP-1 regulates glucose levels by stimulating glucose-dependent insulin secretion and biosynthesis, and by suppressing glucagon secretion, delayed gastric emptying and promoting satiety.

Objectives: To assess the effects of glucagon-like peptide analogues in patients with type 2 diabetes mellitus.

Search strategy: Studies were obtained from electronic searches of The Cochrane Library (last search issue 1, 2011), MEDLINE (last search March 2011), EMBASE (last search March 2011), Web of Science (last search March 2011) and databases of ongoing trials.

Selection criteria: Studies were included if they were randomised controlled trials of a minimum duration of eight weeks comparing a GLP-1 analogue with placebo, insulin, an oral anti-diabetic agent, or another GLP-1 analogue in people with type 2 diabetes.

Data collection and analysis: Data extraction and quality assessment of studies were done by one reviewer and checked by a second. Data were analysed by type of GLP-1 agonist and comparison treatment. Where appropriate, data were summarised in a meta-analysis (mean differences and risk ratios summarised using a random-effects model).

Main results: Seventeen randomised controlled trials including relevant analyses for 6899 participants were included in the analysis. Studies were mostly of short duration, usually 26 weeks.In comparison with placebo, all GLP-1 agonists reduced glycosylated haemoglobin A1c (HbA1c) levels by about 1%. Exenatide 2 mg once weekly and liraglutide 1.8 mg reduced it by 0.20% and 0.24% respectively more than insulin glargine. Exenatide 2 mg once weekly reduced HbA1c more than exenatide 10 μg twice daily, sitagliptin and pioglitazone. Liraglutide 1.8 mg reduced HbA1c by 0.33% more than exenatide 10 μg twice daily. Liraglutide led to similar improvements in HbA1c compared to sulphonylureas but reduced it more than sitagliptin and rosiglitazone.Both exenatide and liraglutide led to greater weight loss than most active comparators, including in participants not experiencing nausea. Hypoglycaemia occurred more frequently in participants taking concomitant sulphonylurea. GLP-1 agonists caused gastrointestinal adverse effects, mainly nausea. These adverse events were strongest at the beginning and then subsided. Beta-cell function was improved with GLP-1 agonists but the effect did not persist after cessation of treatment.None of the studies was long enough to assess long-term positive or negative effects.

Authors' conclusions: GLP-1 agonists are effective in improving glycaemic control.

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Conflict of interest statement

None known.

Figures

1
1
Study flow diagram.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
1.2
1.2. Analysis
Comparison 1 Albiglutide versus placebo, Outcome 2 HbA1c ‐ with plot.
1.5
1.5. Analysis
Comparison 1 Albiglutide versus placebo, Outcome 5 Weight change ‐ with plot.
2.1
2.1. Analysis
Comparison 2 Exenatide 2 mg once weekly versus thiazolidinedione, Outcome 1 HbA1c (%).
2.2
2.2. Analysis
Comparison 2 Exenatide 2 mg once weekly versus thiazolidinedione, Outcome 2 HbA1c
2.3
2.3. Analysis
Comparison 2 Exenatide 2 mg once weekly versus thiazolidinedione, Outcome 3 Hypoglycaemia (minor).
2.4
2.4. Analysis
Comparison 2 Exenatide 2 mg once weekly versus thiazolidinedione, Outcome 4 Weight change (kg).
2.8
2.8. Analysis
Comparison 2 Exenatide 2 mg once weekly versus thiazolidinedione, Outcome 8 Fasting plasma glucose (mmol/L).
3.1
3.1. Analysis
Comparison 3 Exenatide 2 mg once weekly versus DPP‐4 inhibitors, Outcome 1 HbA1c (%).
3.2
3.2. Analysis
Comparison 3 Exenatide 2 mg once weekly versus DPP‐4 inhibitors, Outcome 2 HbA1c
3.3
3.3. Analysis
Comparison 3 Exenatide 2 mg once weekly versus DPP‐4 inhibitors, Outcome 3 Hypoglycaemia (minor).
3.4
3.4. Analysis
Comparison 3 Exenatide 2 mg once weekly versus DPP‐4 inhibitors, Outcome 4 Weight change (kg).
3.8
3.8. Analysis
Comparison 3 Exenatide 2 mg once weekly versus DPP‐4 inhibitors, Outcome 8 Fasting plasma glucose (mmol/L).
4.1
4.1. Analysis
Comparison 4 Exenatide 2 mg once weekly versus insulin glargine, Outcome 1 HbA1c (%).
4.2
4.2. Analysis
Comparison 4 Exenatide 2 mg once weekly versus insulin glargine, Outcome 2 HbA1c
4.3
4.3. Analysis
Comparison 4 Exenatide 2 mg once weekly versus insulin glargine, Outcome 3 Hypoglycaemia (symptoms only).
4.4
4.4. Analysis
Comparison 4 Exenatide 2 mg once weekly versus insulin glargine, Outcome 4 Hypoglycaemia (minor).
4.6
4.6. Analysis
Comparison 4 Exenatide 2 mg once weekly versus insulin glargine, Outcome 6 Weight change (kg).
4.9
4.9. Analysis
Comparison 4 Exenatide 2 mg once weekly versus insulin glargine, Outcome 9 Fasting plasma glucose (mmol/L).
5.1
5.1. Analysis
Comparison 5 Liraglutide 0.6 mg daily versus placebo, Outcome 1 HbA1c (%).
5.2
5.2. Analysis
Comparison 5 Liraglutide 0.6 mg daily versus placebo, Outcome 2 HbA1c
6.1
6.1. Analysis
Comparison 6 Liraglutide 0.9 mg daily versus placebo, Outcome 1 HbA1c (%).
6.2
6.2. Analysis
Comparison 6 Liraglutide 0.9 mg daily versus placebo, Outcome 2 HbA1c
7.1
7.1. Analysis
Comparison 7 Liraglutide 1.2 mg versus placebo, Outcome 1 HbA1c.
7.2
7.2. Analysis
Comparison 7 Liraglutide 1.2 mg versus placebo, Outcome 2 HbA1c
7.3
7.3. Analysis
Comparison 7 Liraglutide 1.2 mg versus placebo, Outcome 3 Hypoglycaemia.
7.4
7.4. Analysis
Comparison 7 Liraglutide 1.2 mg versus placebo, Outcome 4 Weight change.
7.6
7.6. Analysis
Comparison 7 Liraglutide 1.2 mg versus placebo, Outcome 6 Systolic blood pressure.
7.7
7.7. Analysis
Comparison 7 Liraglutide 1.2 mg versus placebo, Outcome 7 Fasting plasma glucose (mmol/L).
7.9
7.9. Analysis
Comparison 7 Liraglutide 1.2 mg versus placebo, Outcome 9 Triglycerides (mmol/L).
7.10
7.10. Analysis
Comparison 7 Liraglutide 1.2 mg versus placebo, Outcome 10 Total cholesterol (mmol/L).
7.11
7.11. Analysis
Comparison 7 Liraglutide 1.2 mg versus placebo, Outcome 11 HDL‐cholesterol (mmol/L).
7.12
7.12. Analysis
Comparison 7 Liraglutide 1.2 mg versus placebo, Outcome 12 LDL‐cholesterol (mmol/L).
8.1
8.1. Analysis
Comparison 8 Liraglutide 1.8 mg versus placebo, Outcome 1 HbA1c.
8.2
8.2. Analysis
Comparison 8 Liraglutide 1.8 mg versus placebo, Outcome 2 HbA1c
8.3
8.3. Analysis
Comparison 8 Liraglutide 1.8 mg versus placebo, Outcome 3 Hypoglycaemia.
8.4
8.4. Analysis
Comparison 8 Liraglutide 1.8 mg versus placebo, Outcome 4 Weight change.
8.6
8.6. Analysis
Comparison 8 Liraglutide 1.8 mg versus placebo, Outcome 6 Systolic blood pressure.
8.7
8.7. Analysis
Comparison 8 Liraglutide 1.8 mg versus placebo, Outcome 7 Fasting plasma glucose (mmol/L).
8.9
8.9. Analysis
Comparison 8 Liraglutide 1.8 mg versus placebo, Outcome 9 Triglycerides (mmol/L).
8.10
8.10. Analysis
Comparison 8 Liraglutide 1.8 mg versus placebo, Outcome 10 Total cholesterol (mmol/L).
8.11
8.11. Analysis
Comparison 8 Liraglutide 1.8 mg versus placebo, Outcome 11 HDL‐cholesterol (mmol/L).
8.12
8.12. Analysis
Comparison 8 Liraglutide 1.8 mg versus placebo, Outcome 12 LDL‐cholesterol (mmol/L).
9.1
9.1. Analysis
Comparison 9 Liraglutide 1.2 mg versus 1.8 mg, Outcome 1 HbA1c.
9.2
9.2. Analysis
Comparison 9 Liraglutide 1.2 mg versus 1.8 mg, Outcome 2 Patients reaching HbA1c
9.3
9.3. Analysis
Comparison 9 Liraglutide 1.2 mg versus 1.8 mg, Outcome 3 Weight.
9.4
9.4. Analysis
Comparison 9 Liraglutide 1.2 mg versus 1.8 mg, Outcome 4 Systolic blood pressure.
10.1
10.1. Analysis
Comparison 10 Liraglutide versus insulin glargine, Outcome 1 HbA1c.
10.2
10.2. Analysis
Comparison 10 Liraglutide versus insulin glargine, Outcome 2 HbA1c
10.3
10.3. Analysis
Comparison 10 Liraglutide versus insulin glargine, Outcome 3 Hypoglycaemia.
10.4
10.4. Analysis
Comparison 10 Liraglutide versus insulin glargine, Outcome 4 Weight change.
10.6
10.6. Analysis
Comparison 10 Liraglutide versus insulin glargine, Outcome 6 Systolic blood pressure.
10.7
10.7. Analysis
Comparison 10 Liraglutide versus insulin glargine, Outcome 7 Fasting plasma glucose (mmol/L).
11.1
11.1. Analysis
Comparison 11 Liraglutide 1.2 mg daily versus thiazolidinedione, Outcome 1 HbA1c (%).
11.2
11.2. Analysis
Comparison 11 Liraglutide 1.2 mg daily versus thiazolidinedione, Outcome 2 HbA1c
11.3
11.3. Analysis
Comparison 11 Liraglutide 1.2 mg daily versus thiazolidinedione, Outcome 3 Hypoglycaemia (mild/moderate/overall).
11.5
11.5. Analysis
Comparison 11 Liraglutide 1.2 mg daily versus thiazolidinedione, Outcome 5 Weight change.
11.9
11.9. Analysis
Comparison 11 Liraglutide 1.2 mg daily versus thiazolidinedione, Outcome 9 Fasting plasma glucose (mmol/L).
12.1
12.1. Analysis
Comparison 12 Liraglutide 1.8 mg daily versus thiazolidinedione, Outcome 1 HbA1c (%).
12.2
12.2. Analysis
Comparison 12 Liraglutide 1.8 mg daily versus thiazolidinedione, Outcome 2 HbA1c
12.3
12.3. Analysis
Comparison 12 Liraglutide 1.8 mg daily versus thiazolidinedione, Outcome 3 Hypoglycaemia.
12.5
12.5. Analysis
Comparison 12 Liraglutide 1.8 mg daily versus thiazolidinedione, Outcome 5 Weight change (kg).
12.9
12.9. Analysis
Comparison 12 Liraglutide 1.8 mg daily versus thiazolidinedione, Outcome 9 Fasting plasma glucose (mmol/L).
13.1
13.1. Analysis
Comparison 13 Liraglutide 1.2 mg daily versus DPP‐4 inhibitors, Outcome 1 HbA1c (%).
13.2
13.2. Analysis
Comparison 13 Liraglutide 1.2 mg daily versus DPP‐4 inhibitors, Outcome 2 HbA1c
13.3
13.3. Analysis
Comparison 13 Liraglutide 1.2 mg daily versus DPP‐4 inhibitors, Outcome 3 Hypoglycaemia (mild/moderate/overall).
13.5
13.5. Analysis
Comparison 13 Liraglutide 1.2 mg daily versus DPP‐4 inhibitors, Outcome 5 Weight change (kg).
13.7
13.7. Analysis
Comparison 13 Liraglutide 1.2 mg daily versus DPP‐4 inhibitors, Outcome 7 Systolic blood pressure (mm Hg).
13.9
13.9. Analysis
Comparison 13 Liraglutide 1.2 mg daily versus DPP‐4 inhibitors, Outcome 9 Fasting plasma glucose (mmol/L).
14.1
14.1. Analysis
Comparison 14 Liraglutide 1.8 mg daily versus DPP‐4 inhibitors, Outcome 1 HbA1c (%).
14.2
14.2. Analysis
Comparison 14 Liraglutide 1.8 mg daily versus DPP‐4 inhibitors, Outcome 2 HbA1c
14.3
14.3. Analysis
Comparison 14 Liraglutide 1.8 mg daily versus DPP‐4 inhibitors, Outcome 3 Hypoglycaemia.
14.5
14.5. Analysis
Comparison 14 Liraglutide 1.8 mg daily versus DPP‐4 inhibitors, Outcome 5 Weight change (kg).
14.7
14.7. Analysis
Comparison 14 Liraglutide 1.8 mg daily versus DPP‐4 inhibitors, Outcome 7 Systolic blood pressure (mm Hg).
14.9
14.9. Analysis
Comparison 14 Liraglutide 1.8 mg daily versus DPP‐4 inhibitors, Outcome 9 Fasting plasma glucose (mmol/L).
15.2
15.2. Analysis
Comparison 15 Lixisenatide versus placebo, Outcome 2 HbA1c
15.3
15.3. Analysis
Comparison 15 Lixisenatide versus placebo, Outcome 3 Symptomatic hypoglycaemia.
15.4
15.4. Analysis
Comparison 15 Lixisenatide versus placebo, Outcome 4 Weight change (kg).
15.6
15.6. Analysis
Comparison 15 Lixisenatide versus placebo, Outcome 6 Fasting plasma glucose (mmol/L).
15.7
15.7. Analysis
Comparison 15 Lixisenatide versus placebo, Outcome 7 Post‐prandial glucose (mmol/L).
15.8
15.8. Analysis
Comparison 15 Lixisenatide versus placebo, Outcome 8 Average self‐monitored 7‐point blood glucose (mmol/L).
16.1
16.1. Analysis
Comparison 16 Liraglutide 1.2 mg versus SU, Outcome 1 HbA1c.
16.3
16.3. Analysis
Comparison 16 Liraglutide 1.2 mg versus SU, Outcome 3 HbA1c
16.4
16.4. Analysis
Comparison 16 Liraglutide 1.2 mg versus SU, Outcome 4 Hypoglycaemia.
16.5
16.5. Analysis
Comparison 16 Liraglutide 1.2 mg versus SU, Outcome 5 Weight change.
16.8
16.8. Analysis
Comparison 16 Liraglutide 1.2 mg versus SU, Outcome 8 Systolic blood pressure.
16.10
16.10. Analysis
Comparison 16 Liraglutide 1.2 mg versus SU, Outcome 10 Fasting plasma glucose (mmol/L).
17.1
17.1. Analysis
Comparison 17 Liraglutide 1.8 mg daily versus SU, Outcome 1 HbA1c (%).
17.3
17.3. Analysis
Comparison 17 Liraglutide 1.8 mg daily versus SU, Outcome 3 HbA1c
17.4
17.4. Analysis
Comparison 17 Liraglutide 1.8 mg daily versus SU, Outcome 4 Hypoglycaemia.
17.5
17.5. Analysis
Comparison 17 Liraglutide 1.8 mg daily versus SU, Outcome 5 Weight change (kg).
17.8
17.8. Analysis
Comparison 17 Liraglutide 1.8 mg daily versus SU, Outcome 8 Systolic blood pressure (mm Hg).
17.10
17.10. Analysis
Comparison 17 Liraglutide 1.8 mg daily versus SU, Outcome 10 Fasting plasma glucose (mmol/L).
18.1
18.1. Analysis
Comparison 18 Taspoglutide versus placebo, Outcome 1 HbA1c (%).
18.3
18.3. Analysis
Comparison 18 Taspoglutide versus placebo, Outcome 3 HbA1c
18.5
18.5. Analysis
Comparison 18 Taspoglutide versus placebo, Outcome 5 Hypoglycaemia.
18.7
18.7. Analysis
Comparison 18 Taspoglutide versus placebo, Outcome 7 Weight change (kg).
18.11
18.11. Analysis
Comparison 18 Taspoglutide versus placebo, Outcome 11 Fasting plasma glucose (mmol/L).
19.4
19.4. Analysis
Comparison 19 LY2189265 versus placebo, Outcome 4 Weight change (kg).
19.6
19.6. Analysis
Comparison 19 LY2189265 versus placebo, Outcome 6 Systolic blood pressure (mm Hg).
19.7
19.7. Analysis
Comparison 19 LY2189265 versus placebo, Outcome 7 Diastolic blood pressure (mm Hg).
20.1
20.1. Analysis
Comparison 20 GLP‐1 agonist versus GLP‐1 agonist, Outcome 1 HbA1c.
20.2
20.2. Analysis
Comparison 20 GLP‐1 agonist versus GLP‐1 agonist, Outcome 2 HbA1c
20.3
20.3. Analysis
Comparison 20 GLP‐1 agonist versus GLP‐1 agonist, Outcome 3 Hypoglycaemia.
20.5
20.5. Analysis
Comparison 20 GLP‐1 agonist versus GLP‐1 agonist, Outcome 5 Weight change.
20.9
20.9. Analysis
Comparison 20 GLP‐1 agonist versus GLP‐1 agonist, Outcome 9 Systolic blood pressure.
20.10
20.10. Analysis
Comparison 20 GLP‐1 agonist versus GLP‐1 agonist, Outcome 10 Fasting plasma glucose (mmol/L).
20.12
20.12. Analysis
Comparison 20 GLP‐1 agonist versus GLP‐1 agonist, Outcome 12 Triglycerides (mmol/L).
20.13
20.13. Analysis
Comparison 20 GLP‐1 agonist versus GLP‐1 agonist, Outcome 13 Total cholesterol (mmol/L).
20.14
20.14. Analysis
Comparison 20 GLP‐1 agonist versus GLP‐1 agonist, Outcome 14 HDL‐cholesterol (mmol/L).
20.15
20.15. Analysis
Comparison 20 GLP‐1 agonist versus GLP‐1 agonist, Outcome 15 LDL‐cholesterol (mmol/L).
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References

References to studies included in this review

A ‐ Rosenstock 2009 {published data only}
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Lixi ‐ Ratner 2010 {published data only}
    1. Ratner RE, Rosenstock J, Boka G, DRI6012 Study Investigators. Dose‐dependent effects of the once‐daily GLP‐1 receptor agonist lixisenatide in patients with Type 2 diabetes inadequately controlled with metformin: a randomized, double‐blind, placebo‐controlled trial. Diabetic Medicine 2010;27(9):1024‐32. - PMC - PubMed
L ‐ Kaku 2010 {published data only}
    1. Kaku K, Rasmussen MF, Clauson P, Seino Y. Improved glycaemic control with minimal hypoglycaemia and no weight change with the once‐daily human glucagon‐like peptide‐1 analogue liraglutide as add‐on to sulphonylurea in Japanese patients with type 2 diabetes. Diabetes Obesity and Metabolism 2010;12:341‐7. - PubMed
L ‐ LEAD 1 Marre 2009 {published data only}
    1. Marre M, Shaw J, Brändle M, Bebakar WMW, Kamaruddin NA, Strand J, et al. Liraglutide, a once‐daily human GLP‐1 analogue, added to a sulphonylurea over 26 weeks produces greater improvements in glycaemic and weight control compared with adding rosiglitazone or placebo in subjects with type 2 diabetes (LEAD‐1 SU). Diabetic Medicine 2009;26:268‐78. - PMC - PubMed
L ‐ LEAD 2 Nauck 2009 {published data only}
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L ‐ LEAD 4 Zinman 2009 {published data only}
    1. Zinman B, Gerich J, Buse JB, Lewin A, Schwartz S, Raskin P, et al. Efficacy and safety of the human glucagon‐like peptide‐1 analog liraglutide in combination with metformin and thiazolidinedione in patients with type 2 diabetes (LEAD‐4 Met+TZD). Diabetes Care 2009;32(7):1224‐30. - PMC - PubMed
L ‐ LEAD 5 Russell‐J 2009 {published data only}
    1. Russell‐Jones D, Vaag A, Schmitz O, Sethi BK, Lalic N, Antic S, et al. Liraglutide vs insulin glargine and placebo in combination with metformin and sulfonylurea therapy in type 2 diabetes mellitus (LEAD‐5 met+SU): a randomised controlled trial. Diabetologia 2009;52:2046‐55. - PMC - PubMed
L ‐ LEAD 6 Buse 2009 {published data only}
    1. Buse J, Sesti G, Schmidt WE, Montanya E, Chang CT, Xu Y, et al. Switching from twice‐daily exenatide to once‐daily liraglutide improves glycemic control in T2D on oral agents. American Diabetes Association. 2009:591‐P. - PMC - PubMed
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L ‐ Pratley 2010 {published data only}
    1. Pratley RE, Nauck M, Bailey T, Montanya E, Cuddihy R, Filetti S, et al. Liraglutide versus sitagliptin for patients with type 2 diabetes who did not have adequate glycaemic control with metformin: a 26‐week, randomised, parallel‐group, open‐label trial. Lancet 2010;375:1447‐56. - PubMed
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T ‐ Nauck 2009 {published data only}
    1. Nauck MA, Ratner RE, Kapitza C, Berria R, Boldrin M, Balena R. Treatment with the human once‐weekly glucagon‐like peptide‐1 analog taspoglutide in combination with metformin improves glycemic control and lowers body weight in patients with type 2 diabetes inadequately controlled with metformin alone: a double‐blind placebo‐controlled study. Diabetes Care 2009;32(7):1237‐43. - PMC - PubMed
T‐ Ratner 2010 {published data only}
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References to studies excluded from this review

Astrup 2009 {published data only}
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    1. Buse JB, Henry RR, Han J, Kim DD, Fineman MS, Baron AD. Effects of exenatide (exendin‐4) on glycemic control over 30 weeks in sulfonylurea‐treated patients with type 2 diabetes. Diabetes Care 2004;27(11):2628‐35. - PubMed
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    1. Feinglos MN, Saad MF, Pi‐Sunyer FX, An B, Santiago O, Liraglutide Dose‐Response Study Group. Effects of liraglutide (NN2211), a long‐acting GLP‐1analogue, on glycaemic control and bodyweight in subjects with type 2 diabetes. Diabetic Medicine 2005;22:1016‐23. - PubMed
Gallwitz 2010 {published data only}
    1. Gallwitz B, Vaag A, Falahati A, Madsbad S. Adding liraglutide to oral antidiabetic drug therapy: onset of treatment effects over time. International Journal of Clinical Practice 2010 Jan;64(2):267‐76. - PubMed
Garber 2009 (LEAD 3) {published data only}
    1. Garber A, Henry R, Ratner R, Garcia‐Hernandez PA, Rodriguez‐Pattzi H, Olvera‐Alvarez I, et al. Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD‐3 Mono): a randomised, 52‐week, phase III, double‐blind, parallel‐treatment trial.[see comment]. Lancet 2009;373(9662):473‐81. - PubMed
Kapitza 2009 {published data only}
    1. Kapitza C, Heise T, Birman P, Jallet K, Ramis J, Balena R. Pharmacokinetic and pharmacodynamic properties of taspoglutide, a once‐weekly, human GLP‐1 analogue, after single‐dose administration in patients with Type 2 diabetes. Diabetic Medicine 2009 Nov;26(11):1156‐64. - PubMed
Kim 2007 {published data only}
    1. Kim D, MacConell L, Zhuang D, Kothare PA, Trautmann M, Fineman M, et al. Effects of once‐weekly dosing of a long‐acting release formulation of exenatide on glucose control and body weight in subjects with type 2 diabetes. Diabetes Care 2007;30:1487‐93. - PubMed
Madsbad 2004 {published data only}
    1. Madsbad S, Schmitz O, Ranstam J, Jakobsen G, Matthews DR, NN2211‐1310 International study group. Improved glycemic control with no weight increase in patients with type 2 diabetes after once‐daily treatment with the long‐acting glucagon‐like peptide 1 analog liraglutide (NN2211). Diabetes Care 2004;27:1335‐42. - PubMed
Malloy 2009 {published data only}
    1. Malloy J, Capparelli E, Gottschalk M, Guan X, Kothare P, Fineman M. Pharmacology and tolerability of a single dose of exenatide in adolescent patients with type 2 diabetes mellitus being treated with metformin: a randomized, placebo‐controlled, single‐blind, dose‐escalation, crossover study. Clinical Therapeutics 2009 Apr;31(4):806‐15. - PubMed
Moretto 2008 {published data only}
    1. Moretto TJ, Milton DR, Ridge TD, Macconell LA, Okerson T, Wolka AM, et al. Efficacy and tolerability of exenatide monotherapy over 24 weeks in antidiabetic drug‐naive patients with type 2 diabetes: a randomized, double‐blind, placebo‐controlled, parallel‐group study. Clinical Therapeutics 2008;30:1448‐60. - PubMed
Nauck 2009 {published data only}
    1. Harder H, Nielsen L, Thi TDT, Astrup A. The effect of liraglutide, a long‐acting glucagon‐like peptide 1 derivative, on glycemic control, body composition, and 24‐h energy expenditure in patients with type 2 diabetes. Diabetes Care 2004;27:1915‐21. - PubMed
    1. Nauck M, Marre M. Adding liraglutide to oral antidiabetic drug monotherapy: efficacy and weight benefits. Postgraduate Medicine 2009;121(3):5‐15. - PubMed
Okerson 2010 {published data only}
    1. Okerson T, Yan P, Stonehouse A, Brodows R. Effects of exenatide on systolic blood pressure in subjects with type 2 diabetes. American Journal of Hypertension 2010 Mar;23(3):334‐39. - PubMed
Riddle 2006 {published data only}
    1. Riddle MC, Henry RR, Poon TH, Zhang B, Mac MS, John HH, et al. Exenatide elicits sustained glycaemic control and progressive reduction of body weight in patients with type 2 diabetes inadequately controlled by sulphonylureas with or without metformin. Diabetes/Metabolism Research and Reviews 2006;22:483‐91. - PubMed
Seino 2008 {published data only}
    1. Seino Y, Rasmussen MF, Zdravkovic M, Kaku K. Dose‐dependent improvement in glycemia with once‐daily liraglutide without hypoglycemia or weight gain: A double‐blind, randomized, controlled trial in Japanese patients with type 2 diabetes. Diabetes Research and Clinical Practice 2008;81(2):161‐8. - PubMed
Trescoli‐Serrano 2005 {published data only}
    1. Trescoli‐Serrano C, Rivas M, Fajardo‐Montanana C, Pino I, Garcia‐Zarco M, Martorrell‐Barraquet A, et al. Clinical site experience comparing insulin glargine with exenatide treatment in type 2 diabetic patients. Diabetologia 2005;48:A3.
Vilsboll 2007 {published data only}
    1. Courreges JP, Vilsboll T, Zdravkovic M, Le‐Thi T, Krarup T, Schmitz O, et al. Beneficial effects of once‐daily liraglutide, a human glucagon‐like peptide‐1 analogue, on cardiovascular risk biomarkers in patients with type 2 diabetes. Diabetic Medicine 2008;25(9):1129‐31. - PMC - PubMed
    1. Horowitz M. Patient‐reported rating of gastrointestinal adverse effects during treatment of type 2 diabetes with the once‐daily human GLP‐1 analogue, liraglutide. Diabetes, Obesity and Metabolism 2008;10:593‐02. - PubMed
    1. Valentine WJ, Hammer M, Palmer AJ, Ray JA. Projecting the long‐term clinical benefits of treatment with the GLP‐1 analogue liraglutide in subjects with type 2 diabetes. Diabetes 2007;56:A568.
    1. Vilsboll T, Brock B, Perrild H, Levin K, Lervang HH, Kolendorf K, et al. Liraglutide, a once‐daily human GLP‐1 analogue, improves pancreatic B‐cell function and arginine‐stimulated insulin secretion during hyperglycaemia in patients with type 2 diabetes mellitus. Diabetic Medicine 2008;25(2):152‐56. - PubMed
    1. Vilsboll T, Zdravkovic M, Le‐Thi T, Krarup T, Schmitz O, Courreges JP, et al. Liraglutide, a long‐acting human glucagon‐like peptide‐1 analog, given as monotherapy significantly improves glycemic control and lowers body weight without risk of hypoglycemia in patients with type 2 diabetes. Diabetes Care 2007;30:1608‐10. - PubMed

References to ongoing studies

Albiglutide NCT00838903 {published data only}
    1. NCT00838903. Efficacy and safety of albiglutide in treatment of type 2 diabetes. http://clinicaltrials.gov/ct2/show/NCT00838903.
Albiglutide NCT00838916 {published data only}
    1. NCT00838916. A study to determine the safety and efficacy of albiglutide in patients with type 2 diabetes. http://clinicaltrials.gov/ct2/show/NCT00838916.
Albiglutide NCT00849017 {published data only}
    1. NCT00849017. Safety and efficacy study of albiglutide in type 2 diabetes. http://clinicaltrials.gov/ct2/show/NCT00849017.
Albiglutide NCT00849056 {published data only}
    1. NCT00849056. Safety and efficacy of albiglutide in type 2 diabetes. http://clinicaltrials.gov/ct2/show/NCT00849056.
Albiglutide NCT01098461 {published data only}
    1. NCT01098461. Dose ranging study of albiglutide in Japanese subjects. http://clinicaltrials.gov/ct2/show/NCT01098461.
Albiglutide NCT01128894 {published data only}
    1. NCT01128894. A study to determine the efficacy and safety of albiglutide as compared with liraglutide.. http://clinicaltrials.gov/ct2/show/NCT01128894 accessed 17 June 2011.
Exenatide QW NCT00641056 {published data only}
    1. NCT00641056. Efficacy of exenatide once weekly and once‐daily insulin glargine in patients with type 2 diabetes treated with metformin alone or in combination with sulfonylurea (DURATION ‐ 3). http://clinicaltrials.gov/ct2/show/NCT00641056.
Exenatide QW NCT00917267 {published data only}
    1. NCT00917267. A study to examine the effects of exenatide once‐weekly injection on glucose control and safety in Asian subjects. http://clinicaltrials.gov/ct2/show/NCT00917267.
Exenatide QW NCT00935532 {published data only}
    1. NCT00935532. Study to evaluate the efficacy and safety of exenatide once‐weekly injection compared to once‐daily insulin in type 2 diabetes mellitus. http://clinicaltrials.gov/ct2/show/NCT00935532.
Exenatide QW NCT01003184 {published data only}
    1. NCT01003184. Efficacy of once‐weekly exenatide versus once or twice daily insulin detemir in patients with type 2 diabetes. http://clinicaltrials.gov/ct2/show/NCT01003184.
Exenatide QW NCT01029886 {published data only}
    1. NCT01029886. Safety and efficacy of exenatide once weekly versus liraglutide in subjects with type 2 diabetes. http://clinicaltrials.gov/ct2/show/NCT01029886 accessed 17 June 2011.
Exenatide QW NCT01144338 {published data only}
    1. NCT01144338. Exenatide study of cardiovascular event lowering trial (EXSCEL): a trial to evaluate cardiovascular outcomes after treatment with exenatide once weekly in patients with type 2 diabetes mellitus. http://clinicaltrials.gov/ct2/show/NCT01144338.
Liraglutide NCT00856986 {published data only}
    1. NCT00856986. The effect of insulin detemir in combination with liraglutide and metformin compared to liraglutide and metformin in subjects with type 2 diabetes. http://clinicaltrials.gov/ct2/show/NCT00856986 accessed 17 June 2011.
Liraglutide NCT01117350 {published data only}
    1. NCT01117350. Efficacy assessment of insulin glargine versus liraglutide after oral agent failure (EAGLE). http://clinicaltrials.gov/ct2/show/NCT01117350 accessed 17 June 2011.
Liraglutide NCT01296412 {published data only}
    1. NCT01296412. Comparison of two treatment regimens (sitagliptin versus liraglutide) on participants who failed to achieve good glucose control on metformin alone (MK‐0431‐403). http://clinicaltrials.gov/ct2/show/NCT01296412 accessed 17 June 2011.
Liraglutide NCT01336023 {published data only}
    1. NCT01336023. Dual action of liraglutide and insulin degludec in type 2 diabetes: a trial comparing the efficacy and safety of insulin degludec/liraglutide, insulin degludec and liraglutide in subjects with type 2 diabetes (DUAL™ I). http://clinicaltrials.gov/ct2/show/NCT01336023 accessed 17 June 2011.
Lixisenatide NCT00707031 {published data only}
    1. NCT00707031. GLP‐1 agonist AVE0010 versus exenatide in patients with type 2 diabetes for glycemic control and safety evaluation, on top of metformin (GETGOAL‐X). http://clinicaltrials.gov/ct2/show/NCT00707031 accessed 17 June 2011.
Lixisenatide NCT00713830 {published data only}
    1. NCT00713830. GLP‐1 agonist AVE0010 in patients with type 2 diabetes for glycemic control and safety evaluation, on top of sulfonylurea (GETGOAL‐S). http://clinicaltrials.gov/ct2/show/NCT00713830 accessed 17 June 2011.
Lixisenatide NCT00763815 {published data only}
    1. NCT00763815. GLP‐1 agonist AVE0010 in patients with type 2 diabetes for glycemic control and safety evaluation, on top of pioglitazone (GETGOAL‐P). http://clinicaltrials.gov/ct2/show/NCT00763815 accessed 17 June 2011.
Lixisenatide NCT00975286 {published data only}
    1. NCT00975286. 24‐week treatment with lixisenatide in type 2 diabetes insufficiently controlled with metformin and insulin glargine. http://clinicaltrials.gov/ct2/show/NCT00975286 accessed 17 June 2011.
Lixisenatide NCT00976937 {published data only}
    1. NCT00976937. 24‐week study comparing lixisenatide to sitagliptin as add‐on to metformin in obese type 2 diabetic patients younger than 50. http://clinicaltrials.gov/ct2/show/NCT00976937 accessed 17 June 2011.
Semaglutide NCT00696657 {published data only}
    1. NCT00696657. A randomised controlled clinical trial in type 2 diabetes comparing semaglutide to placebo and liraglutide. http://clinicaltrials.gov/ct2/show/NCT00696657 accessed 17 June 2011.
Taspoglutide NCT00717457 {published data only}
    1. NCT00717457. A study of taspoglutide versus exenatide for the treatment of patients with type 2 diabetes mellitus inadequately controlled with metformin, thiazolidinedione or a combination of both. http://clinicaltrials.gov/ct2/show/NCT00717457 accessed 17 June 2011.
Taspoglutide NCT00744367 {published data only}
    1. NCT00744367. A study of taspoglutide versus placebo for the treatment of patients with type 2 diabetes mellitus inadequately controlled with metformin plus pioglitazone. http://clinicaltrials.gov/ct2/show/NCT00744367 accessed 17 June 2011.
Taspoglutide NCT00754988 {published data only}
    1. NCT00754988. A study of taspoglutide versus sitagliptin for the treatment of patients with type 2 diabetes mellitus inadequately controlled with metformin. http://clinicaltrials.gov/ct2/show/NCT00754988 accessed 17 June 2011.
Taspoglutide NCT00755287 {published data only}
    1. NCT00755287. A study of the safety, tolerability and effect on glycemic control of taspoglutide versus insulin glargine in insulin naive type 2 diabetic patients inadequately controlled with metformin plus sulphonylurea. http://clinicaltrials.gov/ct2/show/NCT00755287 accessed 17 June 2011.
Taspoglutide NCT00823992 {published data only}
    1. NCT00823992. A study of taspoglutide versus placebo for the treatment of obese patients with type 2 diabetes mellitus inadequately controlled with metformin monotherapy. http://clinicaltrials.gov/ct2/show/NCT00823992 accessed 17 June 2011.
Taspoglutide NCT00909597 {published data only}
    1. NCT00909597. A study of taspoglutide versus pioglitazone in patients with type 2 diabetes. http://clinicaltrials.gov/ct2/show/NCT00909597 accessed 17 June 2011.

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