Skip to main content

Advertisement

Log in

One-year treatment with liraglutide improved renal function in patients with type 2 diabetes: a pilot prospective study

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Unlike GLP-1, liraglutide is not cleared by the glomerulus and its pharmacokinetic is not altered in patients with mild renal impairment. The aim of our study was to analyze the effects of liraglutide on renal function in patients with type 2 diabetes. A twelve-month longitudinal prospective post-marketing study was performed. According to eGFR (estimated glomerular filtration rate) calculated with CKD-EPI equation, 84 consecutive patients were divided in Group A (eGFR > 90 ml/min) and Group B (eGFR < 90 ml/min). BMI, glucose, HbA1c, serum creatinine, microalbuminuria, and eGFR were evaluated at baseline and after 12 months of treatment. A reduction in fasting plasma glucose (p < 0.01), HbA1c (p < 0.003), BMI (p < 0.01), and systolic (p < 0.01) and diastolic blood pressure (p < 0.006) was recorded irrespective of eGFR category. Concerning renal function, creatinine levels had a trend to decrease in both groups. eGFR did not change in Group A, while it increased in Group B (p < 0.05) independently from the concomitant changes of other parameters. Moreover, seven out of 41 patients of Group B had increased eGFR levels which reached the normal values (>90 ml/min). At baseline, five patients had pathological microalbuminuria, but at 12 months three of them returned to normal albuminuria (p < 0.006). Total microalbuminuria levels improved in both groups (p < 0.02). According to preliminary data in animals, our study shows that liraglutide is effective in preserving eGFR in diabetic patients, increasing it in those with reduced renal function. This was associated with a decrease of frequency of patients positive to microalbuminuria. Further studies are needed to confirm these data.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

CKD-EPI:

Chronic kidney disease epidemiology collaboration

eGFR:

Estimated glomerular filtration rate

GLP-1:

Glucose-like peptide 1

MDRD:

Modification of diet in renal disease

NO:

Nitrogen monoxide

References

  1. M. Malm-Erjefält, I. Bjørnsdottir, J. Vanggaard, H. Helleberg, U. Larsen, B. Oosterhuis, Metabolism and excretion of the once-daily human glucagon-like peptide-1 analog liraglutide in healthy male subjects and its in vitro degradation by dipeptidyl peptidase IV and neutral endopeptidase. Drug Metab. Dispos. 38(11), 1944–1953 (2010)

    Article  PubMed  Google Scholar 

  2. J.A. Davidson, J. Brett, A. Falahati, D. Scott, Mild renal impairment and the efficacy and safety of liraglutide. Endocr. Pr. 17(3), 345–355 (2011)

    Article  Google Scholar 

  3. D. Russell-Jones, The safety and tolerability of GLP-1 receptor agonists in the treatment of type-2 diabetes. Int. J. Clin. Pract. 64(10), 1402–1414 (2010)

    Article  CAS  PubMed  Google Scholar 

  4. S. Madsbad, Liraglutide effect and action in diabetes (LEAD™) trials. Expert Rev. Endocrinol. Metab. 4(2), 119–129 (2009)

    Article  Google Scholar 

  5. J.P. Gutzwiller, S. Tschopp, A. Bock, C.E. Zehnder, A.R. Huber, M. Kreyenbuehl et al., Glucagon-like peptide 1 induces natriuresis in healthy subjects and in insulin-resistant obese men. J. Clin. Endocrinol. Metab. 89(6), 3055–3061 (2004)

    Article  CAS  PubMed  Google Scholar 

  6. P. Schlatter, C. Beglinger, J. Drewe, H. Gutmann, Glucagon-like peptide 1 receptor expression in primary porcine proximal tubular cells. Regul. Pept. 141(1–3), 120–128 (2007)

    Article  CAS  PubMed  Google Scholar 

  7. R.O. Crajoinas, F.T. Oricchio, T.D. Pessoa, B.P. Pacheco, L.M. Lessa, G. Malnic et al., Mechanisms mediating the diuretic and natriuretic actions of the incretin hormone glucagon-like peptide-1. Am. J. Physiol. Ren. Physiol. 301(2), 355–363 (2011)

    Article  Google Scholar 

  8. C. Moreno, M. Mistry, R.J. Roman, Renal effects of glucagon-like peptide in rats. Eur. J. Pharmacol. 434(3), 163–167 (2002)

    Article  CAS  PubMed  Google Scholar 

  9. T. Nyström, A.T. Gonon, A. Sjöholm, J. Pernow, Glucagon-like peptide-1 relaxes rat conduit arteries via an endothelium-independent mechanism. Regul. Pept. 125(1–3), 173–177 (2005)

    Article  PubMed  Google Scholar 

  10. C.M. Florkowski, J.S. Chew-Harris, Methods of Estimating GFR - Different Equations Including CKD-EPI. Clin. Biochem. Rev. 32(2), 75–79 (2011)

    PubMed Central  PubMed  Google Scholar 

  11. A.S. Levey, L.A. Stevens, C.H. Schmid, Y. Zhang, A.F. Castro, H.I. Feldman et al., A new equation to estimate glomerular filtration rate. Ann. Intern. Med. 150, 604–612 (2009)

    Article  PubMed Central  PubMed  Google Scholar 

  12. M. Marre, J. Shaw, M. Brändle, W.M. Bebakar, N.A. Kamaruddin, J. Strand, M. Zdravkovic 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. 26(3), 268–278 (2009)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. J.J. Neumiller, T.E. Sonnett, L.D. Wood, S.M. Setter, R.K. Campbell, Pharmacology, efficacy and safety of liraglutide in the management of type 2 diabetes. Diabetes Metab. Syndr. Obes. 3, 215–226 (2010)

    PubMed Central  CAS  PubMed  Google Scholar 

  14. M. Rigato, G.P. Fadini, Comparative effectiveness of liraglutide in the treatment of type 2 diabetes. Diabetes Metab. Syndr. Obes. 7, 107–120 (2014)

    PubMed Central  PubMed  Google Scholar 

  15. G. Aimaretti, Liraglutide: a once-daily human glucagon-like peptide-1 analogue. J. Endocrinol. Invest. 32(8), 701–703 (2009)

    Article  CAS  PubMed  Google Scholar 

  16. R.R. Henry, J.B. Buse, G. Sesti, M.J. Davies, K.H. Jensen, J. Brett et al., Efficacy of antihyperglycemic therapies and the influence of baseline hemoglobin A(1C): a meta-analysis of the liraglutide development program. Endocr. Pract. 17(6), 906–913 (2011)

    Article  PubMed  Google Scholar 

  17. K.Y. Thong, C. Walton, R. Ryder, Safety and efficacy of liraglutide 1.2 mg in patients with mild and moderate renal impairment: the ABCD nationwide liraglutide audit. Prac. Diabetes J. 30(2), 71–76 (2013)

    Article  Google Scholar 

  18. T. Vilsbøll, M. Zdravkovic, T. Le-Thi, T. Krarup, O. Schmitz, J.P. Courrèges 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 30(6), 1608–1610 (2007)

    Article  PubMed  Google Scholar 

  19. B. Wang, J. Zhong, H. Lin, Z. Zhao, Z. Yan, H. He, Y. Ni et al., Blood pressure-lowering effects of GLP-1 receptor agonists exenatide and liraglutide: a meta-analysis of clinical trials. Diabetes Obes. Metab. 15(8), 737–749 (2013)

    Article  CAS  PubMed  Google Scholar 

  20. L. E. Robinson, T. A. Holt, K. Rees, H. S. Randeva, J. P. O’Hare, Effects of exenatide and liraglutide on heart rate, blood pressure and body weight: systematic review and meta-analysis. BMJ Open 3(1), e001986 (2013). doi:10.1136/bmjopen-2012-001986

  21. M. Katout, H. Zhu, J. Rutsky, P. Shah, R.D. Brook, J. Zhong et al., Effect of GLP-1 mimetics on blood pressure and relationship to weight loss and glycemia lowering: results of a systematic meta-analysis and meta-regression. Am. J. Hypertens. 27(1), 130–139 (2014)

    Article  CAS  PubMed  Google Scholar 

  22. K. Okada, K. Kotani, H. Yagyu, A. Ando, J. Osuga, S. Ishibashi, Effects of treatment with liraglutide on oxidative stress and cardiac natriuretic peptide levels in patients with type 2 diabetes mellitus. Endocrine 47(3), 962–964 (2014)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. K. Hirata, S. Kume, S. Araki, M. Sakaguchi, M. Chin-Kanasaki, K. Isshiki et al., Exendin-4 has an anti-hypertensive effect in salt-sensitive mice model. Biochem. Biophys. Res. Commun. 380(1), 44–49 (2009)

    Article  CAS  PubMed  Google Scholar 

  24. P. Anagnostis, V.G. Athyros, F. Adamidou, A. Panagiotou, M. Kita, A. Karagiannis, D.P. Mikhailidis, Glucagon-like peptide-1-based therapies and cardiovascular disease: looking beyond glycaemic control. Diabetes Obes. Metab. 13(4), 302–312 (2011)

    Article  CAS  PubMed  Google Scholar 

  25. L.V. Jacobsen, C. Hindsberger, R. Robson, M. Zdravkovic, Effect of renal impairment on the pharmacokinetics of the GLP-1 analogue liraglutide. Br. J. Clin. Pharmacol. 68(6), 898–905 (2009)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. C.B. Giorda, E. Nada, B. Tartaglino, Pharmacokinetics, safety, and efficacy of DPP-4 inhibitors and GLP-1 receptor agonists in patients with type 2 diabetes mellitus and renal or hepatic impairment. A systematic review of the literature. Endocrine 46(3), 406–419 (2014)

    Article  CAS  PubMed  Google Scholar 

  27. W.J. Liu, S.H. Xie, Y.N. Liu, W. Kim, H.Y. Jin, S.K. Park et al., Dipeptidyl peptidase IV inhibitor attenuates kidney injury in streptozotocin-induced diabetic rats. J. Pharmacol. Exp. Ther. 340(2), 248–255 (2012)

    Article  CAS  PubMed  Google Scholar 

  28. H. Zhang, X. Zhang, C. Hu, W. Lu, Exenatide reduces urinary transforming growth factor-β1 and type IV collagen excretion in patients with type 2 diabetes and microalbuminuria. Kidney Blood Press Res. 35(6), 483–488 (2012)

    Article  CAS  PubMed  Google Scholar 

  29. M. Haluzík, J. Frolík, I. Rychlík, Renal effects of DPP-4 inhibitors: a focus on microalbuminuria. Int. J. Endocrinol. (2013). doi:10.1155/2013/895102

  30. C. Pyke, R.S. Heller, R.K. Kirk, C. Orskov, S. Reedtz-Runge, P. Kaastrup et al., GLP-1 receptor localization in monkey and human tissue: novel distribution revealed with extensively validated monoclonal antibody. Endocrinology 155(4), 1280–1290 (2014)

    Article  PubMed  Google Scholar 

  31. M.J. Lazzara, W.M. Deen, Model of albumin reabsorption in the proximal tubule. Am. J. Physiol. Renal. Physiol. 292(1), 430–439 (2007)

    Article  Google Scholar 

  32. S.P. Marso, N.R. Poulter, S.E. Nissen, M.A. Nauck, B. Zinman, G.H. Daniels et al., Design of the liraglutide effect and action in diabetes: evaluation of cardiovascular outcome results (LEADER) trial. Am. Heart J. 166(5), 823–830 (2013)

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

The authors declare no conflict of interest. There is not conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Statement of Human and Animal Rights

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008.

Statement of Informed Consent

Informed consent was obtained from all patients for being included in the study.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Flavia Prodam.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 18 kb)

Supplementary material 2 (DOC 28 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zavattaro, M., Caputo, M., Samà, M.T. et al. One-year treatment with liraglutide improved renal function in patients with type 2 diabetes: a pilot prospective study. Endocrine 50, 620–626 (2015). https://doi.org/10.1007/s12020-014-0519-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-014-0519-0

Keywords

Navigation