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Type 2 diabetes treatment and progression of chronic kidney disease in Italian family practice

  • Original Article
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Abstract

Aims

Progressive chronic kidney disease represents a dreadful complication of type 2 diabetes mellitus (T2DM). We tested the pattern of use and the renal effects of old glucose-lowering drugs in T2DM patients cared for by Italian general practitioners (GPs).

Methods

Data of 2606 T2DM patients were extracted from the databases of GPs, who do not have access to the most recent glucose-lowering drugs in Italy. The rate of kidney function decline was calculated by CKD-EPIcr, based on two consecutive creatinine values.

Results

Metformin was used in 55% of cases, either alone or with sulfonylureas/repaglinide, across the whole spectrum of CKD (from 66% in stage G1 to only 8% in G4). Sulfonylurea use peaked at 21–22% in stage G2–G3a, whereas repaglinide use significantly increased from 8% in G1 to 22% in G4. The median rate of CKD decline was − 1.64 mL/min/1.73 m2 per year; it was higher in G1 (− 3.22 per year) and progressively lower with CKD severity. 826 cases (31.7%) were classified as fast progressors (eGFR decline more negative than − 5 mL/min/1.73 m2 per year). The risk of fast progressing CKD was associated with increasing BMI, albuminuria, and sulfonylurea use, alone (OR, 1.47; 95% confidence interval, 1.16–1.85), or in association with metformin (OR, 1.40; 95% CI 1.04–1.88). No associations were demonstrated for metformin, cardiovascular and lipid lowering drug use.

Conclusion

In the setting of Italian family practice, sulfonylurea use is associated with progressive CKD in patients with T2DM. Metformin, at doses progressively reduced according to CKD stages, as recommended by guidelines, is not associated with fast progression.

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References

  1. Inzucchi SE, Bergenstal RM, Buse JB et al (2015) Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 38:140–149

    Article  PubMed  Google Scholar 

  2. Pugliese G, Solini A, Bonora E et al (2014) Chronic kidney disease in type 2 diabetes: lessons from the Renal Insufficiency And Cardiovascular Events (RIACE) Italian multicentre study. Nutr Metab Cardiovasc Dis 24:815–822

    Article  CAS  PubMed  Google Scholar 

  3. Afkarian M, Sachs MC, Kestenbaum B et al (2013) Kidney disease and increased mortality risk in type 2 diabetes. J Am Soc Nephrol 24:302–308

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. American Diabetes Association (2016) 5. Glycemic targets. Diabetes Care 39((Suppl 1)):S39–S46

    Google Scholar 

  5. Shurraw S, Hemmelgarn B, Lin M et al (2011) Association between glycemic control and adverse outcomes in people with diabetes mellitus and chronic kidney disease: a population-based cohort study. Arch Intern Med 171:1920–1927

    Article  PubMed  Google Scholar 

  6. American Diabetes Association (2016) 7. Approaches to glycemic treatment. Diabetes Care 39((Suppl 1)):S52–S59

    Google Scholar 

  7. UK Prospective Diabetes Study (UKPDS) Group (1998) Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 352:854–865

    Article  Google Scholar 

  8. Maruthur NM, Tseng E, Hutfless S et al (2016) Diabetes medications as monotherapy or metformin-based combination therapy for type 2 diabetes: a systematic review and meta-analysis. Ann Intern Med 164:740–751

    Article  PubMed  Google Scholar 

  9. Phung OJ, Scholle JM, Talwar M, Coleman CI (2010) Effect of noninsulin antidiabetic drugs added to metformin therapy on glycemic control, weight gain, and hypoglycemia in type 2 diabetes. JAMA 303:1410–1418

    Article  CAS  PubMed  Google Scholar 

  10. Graham GG, Punt J, Arora M et al (2011) Clinical pharmacokinetics of metformin. Clin Pharmacokinet 50:81–98

    Article  CAS  PubMed  Google Scholar 

  11. Kajbaf F, Arnouts P, de Broe M, Lalau JD (2013) Metformin therapy and kidney disease: a review of guidelines and proposals for metformin withdrawal around the world. Pharmacoepidemiol Drug Saf 22:1027–1035

    CAS  PubMed  Google Scholar 

  12. Roumie CL, Hung AM, Greevy RA et al (2012) Comparative effectiveness of sulfonylurea and metformin monotherapy on cardiovascular events in type 2 diabetes mellitus: a cohort study. Ann Intern Med 157:601–610

    Article  PubMed  PubMed Central  Google Scholar 

  13. Marcum ZA, Forsberg CW, Moore KP et al (2018) Mortality associated with metformin versus sulfonylurea initiation: a cohort study of veterans with diabetes and chronic kidney disease. J Gen Intern Med 33:155–165

    Article  PubMed  Google Scholar 

  14. Wu N, Yu X, Greene M, Oderda G (2014) Evaluation of the prevalence of chronic kidney disease and rates of oral antidiabetic prescribing in accordance with guidelines and manufacturer recommendations in type 2 diabetic patients within a long-term care setting. Int J Nephrol 2014:151706

    Article  PubMed  PubMed Central  Google Scholar 

  15. Levey AS, Stevens LA, Schmid CH et al (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150:604–612

    Article  PubMed  PubMed Central  Google Scholar 

  16. Ji M, Lee YH, Hur M et al (2016) Comparing results of five glomerular filtration rate-estimating equations in the Korean general population: MDRD study, revised Lund-Malmo, and three CKD-EPI equations. Ann Lab Med 36:521–528

    Article  PubMed  PubMed Central  Google Scholar 

  17. Stevens PE, Levin A, Kidney Disease: Improving Global Outcomes Chronic Kidney Disease Guideline Development Work Group M (2013) Evaluation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline. Ann Intern Med 158:825–830

    Article  PubMed  Google Scholar 

  18. KDIGO Working Group (2012) KDIGO 2012 Clinical Practice Guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl 3:1–150

    Google Scholar 

  19. Zhang AH, Tam P, LeBlanc D et al (2009) Natural history of CKD stage 4 and 5 patients following referral to renal management clinic. Int Urol Nephrol 41:977–982

    Article  PubMed  Google Scholar 

  20. Associazione Medici Diabetologi (AMD), Società Italiana di Diabetologia (SID) (2018). Standard Italiani per la Cura del Diabete, AMD-SID Publ

  21. CINECA-SID (2017) Osservatorio ARNO-Diabete: Il profilo assistenziale della popolazione con diabete. CINECA-SID, Bologna

    Google Scholar 

  22. Chang CH, Sakaguchi M, Dolin P (2016) Epidemiology of lactic acidosis in type 2 diabetes patients with metformin in Japan. Pharmacoepidemiol Drug Saf 25:1196–1203

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Eppenga WL, Lalmohamed A, Geerts AF et al (2014) Risk of lactic acidosis or elevated lactate concentrations in metformin users with renal impairment: a population-based cohort study. Diabetes Care 37:2218–2224

    Article  CAS  PubMed  Google Scholar 

  24. Inzucchi SE, Lipska KJ, Mayo H, Bailey CJ, McGuire DK (2014) Metformin in patients with type 2 diabetes and kidney disease: a systematic review. JAMA 312:2668–2675

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Kalantar-Zadeh K, Kovesdy CP (2016) Should restrictions be relaxed for metformin use in chronic kidney disease? No, we should never again compromise safety! Diabetes Care 39:1281–1286

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Bakris GL, Molitch ME (2016) Should restrictions be relaxed for metformin use in chronic kidney disease? Yes, they should be relaxed! What’s the fuss? Diabetes Care 39:1287–1291

    Article  CAS  PubMed  Google Scholar 

  27. Lalau JD, Kajbaf F, Bennis Y, Hurtel-Lemaire AS, Belpaire F, De Broe ME (2018) Metformin treatment in patients with type 2 diabetes and chronic kidney disease stages 3A, 3B, or 4. Diabetes Care 41:547–553

    Article  CAS  PubMed  Google Scholar 

  28. Andersen SE, Christensen M (2016) Hypoglycaemia when adding sulphonylurea to metformin: a systematic review and network meta-analysis. Br J Clin Pharmacol 82:1291–1302

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. van Dalem J, Brouwers MC, Stehouwer CD et al (2016) Risk of hypoglycaemia in users of sulphonylureas compared with metformin in relation to renal function and sulphonylurea metabolite group: population based cohort study. BMJ 354:i3625

    Article  PubMed  PubMed Central  Google Scholar 

  30. Marchesini G, Veronese G, Forlani G et al (2014) The management of severe hypoglycemia by the emergency system: the HYPOTHESIS study. Nutr Metab Cardiovasc Dis 24:1181–1188

    Article  CAS  PubMed  Google Scholar 

  31. Kostev K, Dippel FW, Rathmann W (2014) Predictors of insulin initiation in metformin and sulfonylurea users in primary care practices: the role of kidney function. J Diabetes Sci Technol 8:1023–1028

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Christiansen CF, Ehrenstein V, Heide-Jorgensen U et al (2015) Metformin initiation and renal impairment: a cohort study in Denmark and the UK. BMJ Open 5:e008531

    Article  PubMed  PubMed Central  Google Scholar 

  33. Hung AM, Roumie CL, Greevy RA et al (2012) Comparative effectiveness of incident oral antidiabetic drugs on kidney function. Kidney Int 81:698–706

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Sarafidis PA, Bakris GL (2006) Protection of the kidney by thiazolidinediones: an assessment from bench to bedside. Kidney Int 70:1223–1233

    Article  CAS  PubMed  Google Scholar 

  35. Gentile S, Piscitelli P, Viazzi F et al (2017) Antihyperglycemic treatment in patients with type 2 diabetes in Italy: the impact of age and kidney function. Oncotarget 8:62039–62048

    PubMed  PubMed Central  Google Scholar 

  36. Penno G, Solini A, Bonora E et al (2013) Gender differences in cardiovascular disease risk factors, treatments and complications in patients with type 2 diabetes: the RIACE Italian multicentre study. J Intern Med 274:176–191

    Article  CAS  PubMed  Google Scholar 

  37. Ahmadi SF, Zahmatkesh G, Ahmadi E et al (2015) Association of body mass index with clinical outcomes in non-dialysis-dependent chronic kidney disease: a systematic review and meta-analysis. Cardiorenal Med 6:37–49

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Davis E, Campbell K, Gobe G, Hawley C, Isbel N, Johnson DW (2016) Association of anthropometric measures with kidney disease progression and mortality: a retrospective cohort study of pre-dialysis chronic kidney disease patients referred to a specialist renal service. BMC Nephrol 17:74

    Article  PubMed  PubMed Central  Google Scholar 

  39. Gabbay E, Slotki I, Shavit L (2015) Weighing the evidence: obesity, metabolic syndrome, and the risk of chronic kidney disease. BMC Nephrol 16:133

    Article  PubMed  PubMed Central  Google Scholar 

  40. Mallamaci F, Tripepi G (2013) Obesity and CKD progression: hard facts on fat CKD patients. Nephrol Dial Transplant 28(Suppl 4):iv105–iv108

    Article  PubMed  Google Scholar 

  41. Cid Ruzafa J, Paczkowski R, Boye KS et al (2015) Estimated glomerular filtration rate progression in UK primary care patients with type 2 diabetes and diabetic kidney disease: a retrospective cohort study. Int J Clin Pract 69:871–882

    Article  CAS  PubMed  Google Scholar 

  42. De Cosmo S, Viazzi F, Pacilli A et al (2015) Achievement of therapeutic targets in patients with diabetes and chronic kidney disease: insights from the Associazione Medici Diabetologi Annals initiative. Nephrol Dial Transplant 30:1526–1533

    Article  CAS  PubMed  Google Scholar 

  43. Luo Y, Lu K, Liu G, Wang J, Laurent I, Zhou X (2018) The effects of novel antidiabetic drugs on albuminuria in type 2 diabetes mellitus: A systematic review and meta-analysis of randomized controlled trials. Clin Drug Investig. https://doi.org/10.1007/s40261-018-0707-4 (Epub ahead of print, Sep 25)

    Article  PubMed  Google Scholar 

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Acknowledgements

List of participant GPs (Bologna Section of the Italian College of General Practitioners and Primary Care): Antonio Balduzzi, Giulio Bandi, Beatrice Bassi, Paolo Borghi, Loris Brini, Antonino Cammarata, Roberto Casadio, Roberto Cau, Lucia Cecchini, Aurelio Del Vecchio, Maria Immacolata De Vicariis, Shirley Ehrlich, Giuliano Ermini, Livio Franco, Angela Inì, Vincenzo La Fratta, Marco Maccaferri, Angelo Masi, Annunzio Matrà, Piero Mazzetti Gaito, Giampiero Mazzoni, Dante Monti, Mara Mori, Massimo Oggianu, Maria Palasciano, Anna Paternicò, Fernando Perrone, Roberto Pierallini, Stefano Quadrelli, Stefano Rubini, Marcello Salera, Alberto Serio, Antonella Silletti, Elisabetta Simoncini, Luigi Simoni, Pietro Speziali, Cesare Tosetti, Pietro Velonà, Andrea Verri, Domenico Zisa, Donato Zocchi.

Funding

No funding or sponsorship was received for this study or publication of this article.

Author information

Authors and Affiliations

  1. Section of the Italian College of General Practitioners and Primary Care, S.Orsola-Malpighi Hospital, “Alma Mater” University, 9, Via Massarenti, 40138, Bologna, Italy

    G. Ermini, C. Tosetti & D. Zocchi

  2. Nephrology and Dialysis Unit, S. Maria della Scaletta Hospital, Imola, Bologna, Italy

    M. Mandreoli

  3. Unit of Metabolic Diseases and Clinical Dietetics, “Alma Mater” University, Bologna, Italy

    M. T. Caletti & G. Marchesini

Authors
  1. G. Ermini
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  2. C. Tosetti
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  3. D. Zocchi
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  4. M. Mandreoli
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  5. M. T. Caletti
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  6. G. Marchesini
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Consortia

Bologna Section of the Italian College of General Practitioners and Primary Care

  • Antonio Balduzzi
  • , Giulio Bandi
  • , Beatrice Bassi
  • , Paolo Borghi
  • , Loris Brini
  • , Antonino Cammarata
  • , Roberto Casadio
  • , Roberto Cau
  • , Lucia Cecchini
  • , Aurelio Del Vecchio
  • , Maria Immacolata De Vicariis
  • , Shirley Ehrlich
  • , Giuliano Ermini
  • , Livio Franco
  • , Angela Inì
  • , Vincenzo La Fratta
  • , Marco Maccaferri
  • , Angelo Masi
  • , Annunzio Matrà
  • , Piero Mazzetti Gaito
  • , Giampiero Mazzoni
  • , Dante Monti
  • , Mara Mori
  • , Massimo Oggianu
  • , Maria Palasciano
  • , Anna Paternicò
  • , Fernando Perrone
  • , Roberto Pierallini
  • , Stefano Quadrelli
  • , Stefano Rubini
  • , Marcello Salera
  • , Alberto Serio
  • , Antonella Silletti
  • , Elisabetta Simoncini
  • , Luigi Simoni
  • , Pietro Speziali
  • , Cesare Tosetti
  • , Pietro Velonà
  • , Andrea Verri
  • , Domenico Zisa
  •  & Donato Zocchi

Corresponding author

Correspondence to G. Ermini.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

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.

Informed consent

Considering the nature of the study (large retrospective clinical audit, anonymous use of data), the signature of informed consent by individual patients is not mandatory according to Italian law (authorization of privacy guarantor 09/2016.

Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Authorship

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published. All authors had full access to all of the data in this study and take complete responsibility for the integrity of the data and accuracy of the data analysis.

Additional information

Bologna Section of the Italian College of General Practitioners and Primary Care members are given in Acknowledgements section.

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Ermini, G., Tosetti, C., Zocchi, D. et al. Type 2 diabetes treatment and progression of chronic kidney disease in Italian family practice. J Endocrinol Invest 42, 787–796 (2019). https://doi.org/10.1007/s40618-018-0983-0

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  • DOI: https://doi.org/10.1007/s40618-018-0983-0

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