Skip to main content
Erschienen in: Advances in Therapy 11/2014

01.11.2014 | Original Research

Liraglutide for the Treatment of Type 2 Diabetes Mellitus: A Meta-analysis of Randomized Placebo-Controlled Trials

verfasst von: Qiang Du, Yan-Jun Wang, Sheng Yang, Yue-Yang Zhao, Ping Han

Erschienen in: Advances in Therapy | Ausgabe 11/2014

Einloggen, um Zugang zu erhalten

Abstract

Introduction

Liraglutide has been widely used in the treatment of type 2 diabetes mellitus (T2DM), however, the results of a number of randomized placebo-controlled trials on the effects of liraglutide for the treatment of T2DM have varied. The purpose of this study was to assess the effects of liraglutide versus placebo for the treatment of T2DM.

Methods

We searched randomized controlled trials comparing liraglutide and placebo for the treatment of T2DM in the following databases: MEDLINE; EMBASE; Cochrane Library Central Register of Controlled Trials; and Clinical Trials Gov (through August 2014). The standard mean difference (SMD) was calculated for the continuous data and a χ 2 test was used to evaluate heterogeneity.

Results

Initially, 103 articles were retrieved through the literature search and 11 studies met the requirements for the meta-analysis. The effects of liraglutide on lowering glycosylated hemoglobin, fasting plasma glucose, reducing weight, lowering blood pressure, and the prevalence of adverse events were significantly different from placebo (P < 0.0001, SMD = −0.96, 95% CI = [−1.20, −0.73]; P < 0.0001, SMD = −0.72, 95% CI = [−0.99, −0.45]; P = 0.004, SMD = −0.24, 95% CI = [−0.40, −0.07]; P = 0.021, SMD = −0.15, 95% CI = [−0.27, −0.02], and P = 0.007, respectively).

Conclusion

Liraglutide had greater hypoglycemic, weight-reducing and systolic blood pressure-lowering effects than placebo. However, there were more adverse events in the treatment with liraglutide. It is suggested that additional well-designed, large, studies be conducted to further support the use of liraglutide and provide objective guidance for clinical application of liraglutide.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Unwin N, Guariguata L, Whiting D, et al. Complementary approaches to estimation of the global burden of diabetes. Lancet. 2012;379:1487–8.PubMedCrossRef Unwin N, Guariguata L, Whiting D, et al. Complementary approaches to estimation of the global burden of diabetes. Lancet. 2012;379:1487–8.PubMedCrossRef
2.
Zurück zum Zitat Guariguata L, Whiting DR, Hambleton I, et al. Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract. 2014;103:137–49.PubMedCrossRef Guariguata L, Whiting DR, Hambleton I, et al. Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract. 2014;103:137–49.PubMedCrossRef
3.
Zurück zum Zitat Rosberger DF. Diabetic retinopathy: current concepts and emerging therapy. Endocrinol Metab Clin North Am. 2013;42:721–45.PubMedCrossRef Rosberger DF. Diabetic retinopathy: current concepts and emerging therapy. Endocrinol Metab Clin North Am. 2013;42:721–45.PubMedCrossRef
5.
Zurück zum Zitat Xu Q, Pan J, Yu J, et al. Meta-analysis of methylcobalamin alone and in combination with lipoic acid in patients with diabeticperipheral neuropathy. Diabetes Res Clin Pract. 2013;101:99–105.PubMedCrossRef Xu Q, Pan J, Yu J, et al. Meta-analysis of methylcobalamin alone and in combination with lipoic acid in patients with diabeticperipheral neuropathy. Diabetes Res Clin Pract. 2013;101:99–105.PubMedCrossRef
6.
7.
Zurück zum Zitat Lachin JM, Orchard TJ. Nathan DM; DCCT/EDIC Research Group. Update on cardiovascular outcomes at 30 years of the diabetes control and complications trial/epidemiology of diabetes interventions and complications study. Diabetes Care. 2014;37:39–43.PubMedCrossRef Lachin JM, Orchard TJ. Nathan DM; DCCT/EDIC Research Group. Update on cardiovascular outcomes at 30 years of the diabetes control and complications trial/epidemiology of diabetes interventions and complications study. Diabetes Care. 2014;37:39–43.PubMedCrossRef
8.
Zurück zum Zitat Gubitosi-Klug RA; DCCT/EDIC Research Group. The diabetes control and complications trial/epidemiology of diabetes interventions and complications study at 30 years: summary and future directions. Diabetes Care. 2014;37:44–9.CrossRef Gubitosi-Klug RA; DCCT/EDIC Research Group. The diabetes control and complications trial/epidemiology of diabetes interventions and complications study at 30 years: summary and future directions. Diabetes Care. 2014;37:44–9.CrossRef
9.
Zurück zum Zitat Schofield D, Cunich MM, Shrestha RN, et al. The economic impact of diabetes through lost labour force participation on individuals and government: evidence from a microsimulation model. BMC Public Health. 2014;14:220.PubMedCentralPubMedCrossRef Schofield D, Cunich MM, Shrestha RN, et al. The economic impact of diabetes through lost labour force participation on individuals and government: evidence from a microsimulation model. BMC Public Health. 2014;14:220.PubMedCentralPubMedCrossRef
10.
Zurück zum Zitat Meyers JL, Parasuraman S, Bell KF, et al. The high-cost, type 2 diabetes mellitus patient: an analysis of managed care administrative data. Arch Public Health. 2014;72:6.PubMedCentralPubMedCrossRef Meyers JL, Parasuraman S, Bell KF, et al. The high-cost, type 2 diabetes mellitus patient: an analysis of managed care administrative data. Arch Public Health. 2014;72:6.PubMedCentralPubMedCrossRef
11.
Zurück zum Zitat Asao K, Kaminski J, McEwen LN, et al. Assessing the burden of diabetes mellitus in emergency departments in the United States: The National Hospital Ambulatory Medical Care Survey (NHAMCS). J Diabetes Complic. 2014;S1056–8727:00047–56. Asao K, Kaminski J, McEwen LN, et al. Assessing the burden of diabetes mellitus in emergency departments in the United States: The National Hospital Ambulatory Medical Care Survey (NHAMCS). J Diabetes Complic. 2014;S1056–8727:00047–56.
12.
13.
Zurück zum Zitat Higgins JP, Thompson S. Quantifying heterogeneity in a meta-analysis. In: Higgins JP, Thompson S, editors. Statistics in Medicine. Hoboken: Wiley; 2002. Higgins JP, Thompson S. Quantifying heterogeneity in a meta-analysis. In: Higgins JP, Thompson S, editors. Statistics in Medicine. Hoboken: Wiley; 2002.
14.
Zurück zum Zitat Li CJ, Li J, Zhang QM, et al. Efficacy and safety comparison between liraglutide as add-on therapy to insulin and insulin dose-increase in Chinese subjects with poorly controlled type 2 diabetes and abdominal obesity. Cardiovasc Diabetol. 2012;11:142.PubMedCentralPubMedCrossRef Li CJ, Li J, Zhang QM, et al. Efficacy and safety comparison between liraglutide as add-on therapy to insulin and insulin dose-increase in Chinese subjects with poorly controlled type 2 diabetes and abdominal obesity. Cardiovasc Diabetol. 2012;11:142.PubMedCentralPubMedCrossRef
15.
Zurück zum Zitat Forst T, Michelson G, Ratter F, et al. Addition of liraglutide in patients with Type 2 diabetes well controlled on metformin monotherapy improves several markers of vascular function. Diabet Med. 2012;29:1115–8.PubMedCrossRef Forst T, Michelson G, Ratter F, et al. Addition of liraglutide in patients with Type 2 diabetes well controlled on metformin monotherapy improves several markers of vascular function. Diabet Med. 2012;29:1115–8.PubMedCrossRef
16.
Zurück zum Zitat Kaku K, Rasmussen MF, Clauson P, et al. 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 Obes Metab. 2010;12:341–7.PubMedCrossRef Kaku K, Rasmussen MF, Clauson P, et al. 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 Obes Metab. 2010;12:341–7.PubMedCrossRef
17.
Zurück zum Zitat Russell-Jones D, Vaag A, Schmitz O, et al. Liraglutide Effect and Action in Diabetes 5 (LEAD-5) met + SU Study Group. 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.PubMedCentralPubMedCrossRef Russell-Jones D, Vaag A, Schmitz O, et al. Liraglutide Effect and Action in Diabetes 5 (LEAD-5) met + SU Study Group. 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.PubMedCentralPubMedCrossRef
18.
Zurück zum Zitat Marre M, Shaw J, Brändle M, et al. LEAD-1 SU study group. 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). Diabet Med. 2009;26:268–78.PubMedCentralPubMedCrossRef Marre M, Shaw J, Brändle M, et al. LEAD-1 SU study group. 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). Diabet Med. 2009;26:268–78.PubMedCentralPubMedCrossRef
19.
Zurück zum Zitat Zinman B, Gerich J, Buse JB, et al. LEAD-4 Study Investigators. 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;32:1224–30.PubMedCentralPubMedCrossRef Zinman B, Gerich J, Buse JB, et al. LEAD-4 Study Investigators. 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;32:1224–30.PubMedCentralPubMedCrossRef
20.
Zurück zum Zitat Nauck M, Frid A, Hermansen K, et al. LEAD-2 Study Group. Efficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin, in type 2 diabetes: the LEAD (liraglutide effect and action in diabetes)-2 study. Diabetes Care. 2009;32:84–90.PubMedCentralPubMedCrossRef Nauck M, Frid A, Hermansen K, et al. LEAD-2 Study Group. Efficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin, in type 2 diabetes: the LEAD (liraglutide effect and action in diabetes)-2 study. Diabetes Care. 2009;32:84–90.PubMedCentralPubMedCrossRef
21.
Zurück zum Zitat Seino Y, Rasmussen MF, Zdravkovic M, et al. 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 Res Clin Pract. 2008;81:161–8.PubMedCrossRef Seino Y, Rasmussen MF, Zdravkovic M, et al. 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 Res Clin Pract. 2008;81:161–8.PubMedCrossRef
22.
Zurück zum Zitat Vilsbøll T, Brock B, Perrild H, 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. Diabetes Med. 2008;25:152–6.CrossRef Vilsbøll T, Brock B, Perrild H, 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. Diabetes Med. 2008;25:152–6.CrossRef
23.
Zurück zum Zitat Harder H, Nielsen L, Tu DT, et al. 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.PubMedCrossRef Harder H, Nielsen L, Tu DT, et al. 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.PubMedCrossRef
24.
Zurück zum Zitat Degn KB, Juhl CB, Sturis J, et al. One week’s treatment with the long-acting glucagon-like peptide 1 derivative liraglutide (NN2211) markedly improves 24-h glycemia and alpha- and beta-cell function and reduces endogenous glucose release in patients with type 2 diabetes. Diabetes. 2004;53:1187–94.PubMedCrossRef Degn KB, Juhl CB, Sturis J, et al. One week’s treatment with the long-acting glucagon-like peptide 1 derivative liraglutide (NN2211) markedly improves 24-h glycemia and alpha- and beta-cell function and reduces endogenous glucose release in patients with type 2 diabetes. Diabetes. 2004;53:1187–94.PubMedCrossRef
25.
Zurück zum Zitat Panic N, Leoncini E, de Belvis G, et al. Evaluation of the endorsement of the preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement on the quality of published systematic review and meta-analyses. PLoS One. 2013;8:e83138.PubMedCentralPubMedCrossRef Panic N, Leoncini E, de Belvis G, et al. Evaluation of the endorsement of the preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement on the quality of published systematic review and meta-analyses. PLoS One. 2013;8:e83138.PubMedCentralPubMedCrossRef
26.
Zurück zum Zitat Henning CH, Zarnekow N, Hedtrich J, et al. Identification of direct and indirect social network effects in the pathophysiology of insulin resistance in obese human subjects. PLoS One. 2014;9:e93860.PubMedCentralPubMedCrossRef Henning CH, Zarnekow N, Hedtrich J, et al. Identification of direct and indirect social network effects in the pathophysiology of insulin resistance in obese human subjects. PLoS One. 2014;9:e93860.PubMedCentralPubMedCrossRef
27.
Zurück zum Zitat Russell-Jones D, Khan R. Insulin-associated weight gain in diabetes—causes, effects and coping strategies. Diabetes Obes Metab. 2007;9:799–812.PubMedCrossRef Russell-Jones D, Khan R. Insulin-associated weight gain in diabetes—causes, effects and coping strategies. Diabetes Obes Metab. 2007;9:799–812.PubMedCrossRef
29.
Zurück zum Zitat Bader G, Geransar P, Schweizer A. Vildagliptin more effectively achieves a composite endpoint of HbA1c < 7.0% without hypoglycaemia and weight gain compared with glimepiride after 2 years of treatment. Diabetes Res Clin Pract. 2013;100:e78–81.PubMedCrossRef Bader G, Geransar P, Schweizer A. Vildagliptin more effectively achieves a composite endpoint of HbA1c < 7.0% without hypoglycaemia and weight gain compared with glimepiride after 2 years of treatment. Diabetes Res Clin Pract. 2013;100:e78–81.PubMedCrossRef
30.
Zurück zum Zitat Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med. 2007;356:2457–571.PubMedCrossRef Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med. 2007;356:2457–571.PubMedCrossRef
31.
Zurück zum Zitat Singh S, Loke YK, Furberg CD. Long-term risk of cardiovascular events with rosiglitazone: a meta-analysis. JAMA. 2007;298:1189–95.PubMedCrossRef Singh S, Loke YK, Furberg CD. Long-term risk of cardiovascular events with rosiglitazone: a meta-analysis. JAMA. 2007;298:1189–95.PubMedCrossRef
32.
Zurück zum Zitat Kim SH, Liu A, Ariel D, et al. Pancreatic beta cell function following liraglutide-augmented weight loss in individuals with prediabetes: analysis of a randomised, placebo-controlled study. Diabetologia. 2014;57:455–62.PubMedCrossRef Kim SH, Liu A, Ariel D, et al. Pancreatic beta cell function following liraglutide-augmented weight loss in individuals with prediabetes: analysis of a randomised, placebo-controlled study. Diabetologia. 2014;57:455–62.PubMedCrossRef
33.
Zurück zum Zitat Luo X, Pan L, Nie A, et al. Liraglutide protects pancreatic beta cells during an early intervention in Gato-Kakizaki rats. J Diabetes. 2013;5:421–8.PubMedCrossRef Luo X, Pan L, Nie A, et al. Liraglutide protects pancreatic beta cells during an early intervention in Gato-Kakizaki rats. J Diabetes. 2013;5:421–8.PubMedCrossRef
34.
Zurück zum Zitat Parthsarathy V, Hölscher C. Chronic treatment with the GLP1 analogue liraglutide increases cell proliferation and differentiation into neurons in an AD mouse model. PLoS One. 2013;8:e58784.PubMedCentralPubMedCrossRef Parthsarathy V, Hölscher C. Chronic treatment with the GLP1 analogue liraglutide increases cell proliferation and differentiation into neurons in an AD mouse model. PLoS One. 2013;8:e58784.PubMedCentralPubMedCrossRef
35.
Zurück zum Zitat Elkhenini H, New JP, Summers LK, et al. Liraglutide therapy in obese people with type 2 diabetes—Experience of a weight management centre. Eur J Intern Med. 2014;25:e38–9.PubMedCrossRef Elkhenini H, New JP, Summers LK, et al. Liraglutide therapy in obese people with type 2 diabetes—Experience of a weight management centre. Eur J Intern Med. 2014;25:e38–9.PubMedCrossRef
36.
Zurück zum Zitat Robinson LE, Holt TA, Rees K, et al. Effects of exenatide and liraglutide on heart rate, blood pressure and body weight: systematic review and meta-analysis. BMJ Open. 2013;3:e001986.PubMedCentralPubMed Robinson LE, Holt TA, Rees K, et al. Effects of exenatide and liraglutide on heart rate, blood pressure and body weight: systematic review and meta-analysis. BMJ Open. 2013;3:e001986.PubMedCentralPubMed
37.
Zurück zum Zitat Wang B, Zhong J, Lin H, et al. Blood pressure-lowering effects of GLP-1 receptor agonists exenatide and liraglutide: a meta-analysis of clinical trials. Diabetes Obes Metab. 2013;15:737–49.PubMedCrossRef Wang B, Zhong J, Lin H, et al. Blood pressure-lowering effects of GLP-1 receptor agonists exenatide and liraglutide: a meta-analysis of clinical trials. Diabetes Obes Metab. 2013;15:737–49.PubMedCrossRef
Metadaten
Titel
Liraglutide for the Treatment of Type 2 Diabetes Mellitus: A Meta-analysis of Randomized Placebo-Controlled Trials
verfasst von
Qiang Du
Yan-Jun Wang
Sheng Yang
Yue-Yang Zhao
Ping Han
Publikationsdatum
01.11.2014
Verlag
Springer Healthcare
Erschienen in
Advances in Therapy / Ausgabe 11/2014
Print ISSN: 0741-238X
Elektronische ISSN: 1865-8652
DOI
https://doi.org/10.1007/s12325-014-0164-2

Weitere Artikel der Ausgabe 11/2014

Advances in Therapy 11/2014 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Reizdarmsyndrom: Diäten wirksamer als Medikamente

29.04.2024 Reizdarmsyndrom Nachrichten

Bei Reizdarmsyndrom scheinen Diäten, wie etwa die FODMAP-arme oder die kohlenhydratreduzierte Ernährung, effektiver als eine medikamentöse Therapie zu sein. Das hat eine Studie aus Schweden ergeben, die die drei Therapieoptionen im direkten Vergleich analysierte.

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.