Acta Diabetologica

, Volume 51, Issue 5, pp 853–863

Prevention of type 2 diabetes in obese at-risk subjects: a systematic review and meta-analysis

  • Claudia Merlotti
  • Alberto Morabito
  • Valerio Ceriani
  • Antonio E. Pontiroli
Original Article


Different intervention strategies can prevent new cases of type 2 diabetes (T2DM) in obese subjects. The present systematic review and meta-analysis evaluates the effectiveness of different strategies in prevention of type 2 diabetes in obese subjects. Studies were grouped into five different strategies: (1) physical activity ± diet; (2) anti-diabetic drugs (glitazones, metformin, glinides, alfa-glucosidase inhibitors); (3) antihypertensive drugs (ACE inhibitors, ARB); (4) weight loss-promoting drugs and lipid-lowering drugs (orlistat, bezafibrate, phentermine/topiramate controlled release); and (5) bariatric surgery. Only controlled studies, dealing with subjects BMI ≥ 30 kg/m2, were included in the analysis, whether randomized or non-randomized studies. Appropriate methodology (PRISMA statement) was adhered to. Publication bias was formally assessed. Eighteen studies (43,669 subjects, 30,774 with impaired glucose tolerance and/or impaired fasting glucose), published in English language as full papers, were analyzed to identify predictors of new cases of T2DM and were included in a meta-analysis (random-effects model) to study the effect of different strategies. Intervention effect (new cases of diabetes) was expressed as odds ratio (OR), with 95 % confidence intervals (CIs). In obese subjects, non-surgical strategies were able to prevent T2DM, with different effectiveness [OR from 0.44 (0.36–0.52) to 0.86 (0.80–0.92)]; in morbidly obese subjects, bariatric surgery was highly effective [OR = 0.10 (0.02–0.49)]. At meta-regression analysis, factors associated with effectiveness were weight loss, young age and fasting insulin levels. Publication bias was present only when considering all studies together. These data indicate that several strategies, with different effectiveness, can prevent T2DM in obese subjects.


Obesity Type 2 diabetes Meta-analysis Prevention Lifestyle modifications Anti-diabetic drugs Bariatric surgery 

Supplementary material

592_2014_624_MOESM1_ESM.ppt (1.9 mb)
Supplementary material 1 (PPT 1966 kb)


  1. 1.
    American Diabetes Association. Total prevalence of diabetes and pre-diabetes. American Association website.
  2. 2.
    Pi-Sunyer X (2009) The medical risk of obesity. Postgrad Med 121:21–33PubMedCrossRefPubMedCentralGoogle Scholar
  3. 3.
    Despres JP, Lemieux I (2006) Abdominal obesity and metabolic syndrome. Nature 444:881–887PubMedCrossRefGoogle Scholar
  4. 4.
    Ford ES, Zhao G, Li C et al (2010) Pre-diabetes and the risk for cardiovascular disease: a systematic review of the evidence. J Am Coll Cardiol 55:1310–1317PubMedCrossRefGoogle Scholar
  5. 5.
    Cheng YJ, Gregg EW, Geiss LS et al (2009) Association of HbA1c and fasting plasma glucose level with diabetic retinopathy prevalence in the U.S. population: implication for diabetes diagnostic thresholds. Diabetes Care 32:2027–2032PubMedCrossRefPubMedCentralGoogle Scholar
  6. 6.
    Ziegler D, Rathmann W, Dickhaus T et al (2008) Prevalence of polyneuropathy in prediabetes and diabetes is associated with abdominal obesity and macroangiopathy: the MONICA/KORA Augsburg Survey S2 and S3. Diabetes Care 31:464–469PubMedCrossRefGoogle Scholar
  7. 7.
    CDC. Diabetes Fact Sheet online 2011. Jan 26.2011Google Scholar
  8. 8.
    American Diabetes Association (2012) Standards of medical care in diabetes-2012. Diabetes Care 35:S11–S63CrossRefGoogle Scholar
  9. 9.
    Nathan DM, Davidson MB, DeFronzo RA et al (2007) Impaired fasting glucose and impaired glucose tolerance: implication for care. Diabetes Care 30:753–759PubMedCrossRefGoogle Scholar
  10. 10.
    Brakis G, Stockert J, Molitch M et al (2009) Risk factor assessment for new onset diabetes: literature review. Diabetes Obes Metab 11:177–187CrossRefGoogle Scholar
  11. 11.
    Progetto Cuore. Istituto Superiore di Sanità. Accessed 13 June 2012
  12. 12.
    Whiting DR, Guariguata L, Weil C, Shaw J (2011) IDF diabetes atlas: global estimates of the prevalence of diabetes for 2011 and 2030. Diabetes Res Clin Pract 94:311–321PubMedCrossRefGoogle Scholar
  13. 13.
    Perrault L, Pan Q, Mather KJ et al (2012) Regression from pre-diabetes to normal glucose regulation is associated with long term reduction in diabetes risk: results from the Diabetes Prevention Program Outcomes Study. Lancet 379:2243–2251CrossRefGoogle Scholar
  14. 14.
    Phung OJ, Sood NA, Sill BE, Coleman CI (2011) Oral anti-diabetic drugs for the prevention of type 2 diabetes. Diabet Med 28:948–964PubMedCrossRefGoogle Scholar
  15. 15.
    Knowler WC, Barrett-Connor E, Fowler SE, The Diabetes Prevention Program Research Group et al (2002) Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 346:393–403PubMedCrossRefGoogle Scholar
  16. 16.
    Lindstrom J, Ilanne-Parikka P, Peltonen M, Aunola S et al (2006) Sustained reduction in the incidence of type 2 diabetes by lifestyle intervention: follow-up of the Finnish Diabetes Prevention Study. Lancet 368:1673–1679PubMedCrossRefGoogle Scholar
  17. 17.
    Penn L, White M, Oldroyd J et al (2009) Prevention 006Ff type 2 diabetes in adults with impaired glucose tolerance: the European diabetes prevention RCT in newcastle upon Tyne UK. BMC Public Health 9:342PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Penn L, White M, Lindstrom J, den Boer A et al (2013) Importance of weight loss maintenance and risk prediction in the prevention of type 2 diabetes: analysis of the European Diabetes Prevention Study RCT. PLoS One 8:e57143PubMedCrossRefPubMedCentralGoogle Scholar
  19. 19.
    Buchanan TA, Xiang AH, Peters RK et al (2002) Preservation of pancreatic β-cell function and prevention of type 2 diabetes by pharmacological treatment of insulin resistance in high–risk Hispanic women. Diabetes 51:2796–2803PubMedCrossRefGoogle Scholar
  20. 20.
    Chiasson JL, Josse RG, Gomis R (2002) Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomised trial. Lancet 359:2072–2077PubMedCrossRefGoogle Scholar
  21. 21.
    Gerstein HC, Yusuf S, Bosch J, The Dream Trial Investigators et al (2006) Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial. Lancet 368:1096–1105PubMedCrossRefGoogle Scholar
  22. 22.
    Holman RR, Haffner SM, McMurray JJ, The NAVIGATOR Study Group et al (2010) Effect of nateglinide on the incidence of diabetes and cardiovascular events. N Engl J Med 362:1463–1476PubMedCrossRefGoogle Scholar
  23. 23.
    DeFronzo RA, Tripathy D, Schwenke DC, The ACT NOW Study et al (2011) Pioglitazone for diabetes prevention in impaired glucose tolerance. N Engl J Med 364:1104–1115PubMedCrossRefGoogle Scholar
  24. 24.
    Gerstein HC, Mohan V, Avezum A et al (2011) Long term effect of rosiglitazone and/or ramipril on the incidence of diabetes. Diabetologia 54:487–495PubMedCrossRefGoogle Scholar
  25. 25.
    Bosch J, Yusuf S, Gerstein HC, For the Dream Trial Investigators et al (2006) Effect of ramipril on the incidence of diabetes. N Engl J Med 355:1551–1562PubMedCrossRefGoogle Scholar
  26. 26.
    Mc Murray JJ, Holman RR, Haffner SM et al (2010) Effect of valsartan on the incidence of diabetes and cardiovascular events. N Engl J Med 362:1477–1490CrossRefGoogle Scholar
  27. 27.
    Torgerson JS, Hauptman J, Boldrin MN et al (2004) XENical in the Prevention of Diabetes in Obese Subjects (XENDOS) Study. A randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Diabetes Care 27:155–161PubMedCrossRefGoogle Scholar
  28. 28.
    Tenenbaum A, Motro M, Fisman EZ et al (2005) Effect of bezafibrate on incidence of type 2 diabetes mellitus in obese patients. Eur Heart J 26:2032–2038PubMedCrossRefGoogle Scholar
  29. 29.
    Garvey T, Ryan DH, Henry R et al (2014) Prevention of type 2 diabetes in subjects with prediabetes and metabolic syndrome with phentermine and topiramate extended-release. Diabetes Care 37:912–921PubMedCrossRefGoogle Scholar
  30. 30.
    Long SD, O’Brien K, MacDonald KG et al (1994) Weight loss in severely obese subjects prevents progression of impaired glucose tolerance to type II diabetes. A longitudinal interventional study. Diabetes Care 17:372–375PubMedCrossRefGoogle Scholar
  31. 31.
    Pontiroli AE, Folli F, Paganelli M et al (2005) Laparoscopic gastric banding prevents type 2 diabetes and arterial hypertension and induces their remission in morbid obesity. A 4-year case-controlled study. Diabetes Care 28:2703–2709PubMedCrossRefGoogle Scholar
  32. 32.
    Carlsson LM, Peltonen M, Ahlin S et al (2012) Bariatric surgery and prevention of type 2 diabetes in Swedish obese subjects. N Engl J Med 367:695–704PubMedCrossRefGoogle Scholar
  33. 33.
    Yamaoka K, Tango T (2005) Efficacy of lifestyle education to prevent type 2 diabetes. A meta-analysis of randomized controlled trials. Diabetes Care 28:2780–2786PubMedCrossRefGoogle Scholar
  34. 34.
    Norris SL, Zhang X, Avenell A et al (2005) Long term effectiveness of weight-loss interventions in adults with pre-diabetes. A review. Am J Prev Med 28:126–139PubMedCrossRefGoogle Scholar
  35. 35.
    Lloret-Linares C, Greenfield JR, Czernichow S (2008) Effect of weight reducing agents on glycaemic parameters and progression to type 2 diabetes: a review. Diabet Med 25:1142–1150PubMedCrossRefGoogle Scholar
  36. 36.
    Yates T, Khunti K, Bull F et al (2007) The role of physical activity in the management of impaired glucose tolerance: a systematic review. Diabetologia 50:1116–1126PubMedCrossRefPubMedCentralGoogle Scholar
  37. 37.
    Anderson DC (2005) Pharmacologic prevention or delay of type 2 diabetes mellitus. Ann Pharmacother 39:102–109PubMedCrossRefGoogle Scholar
  38. 38.
    Padwal R, Majumdar SR, Johnson JA et al (2005) A systematic review of drug therapy to delay or prevent type 2 diabetes. Diabetes Care 28:736–744PubMedCrossRefGoogle Scholar
  39. 39.
    Abuissa H, Jones PG, Marso SP, O’Keefe JH Jr (2005) Angiotensin-Converting enzyme inhibitors or angiotensin receptor blockers for prevention of type 2 diabetes. A meta-analysis of randomized clinical trials. J Am Coll Cardiol 46:821–826PubMedCrossRefGoogle Scholar
  40. 40.
    Andraws R, Brown DL (2007) Effect of inhibitors of the renin-angiotensin system on the development of type 2 diabetes mellitus (meta-analysis of randomized trials). Am J Cardiol 99:1006–1012PubMedCrossRefGoogle Scholar
  41. 41.
    Abuissa H, O’Keefe J (2008) The role of renin-angiotensin-aldosterone system-based therapy in diabetes prevention and cardiovascular and renal protection. Diabetes Obes Metab 10:1157–1166PubMedGoogle Scholar
  42. 42.
    Higgins JPT, Green S (eds) (2008) Cochrane handbook for systematic reviews. Special topics in statistics: studies with more than two intervention groups. Wiley, BlackwellGoogle Scholar
  43. 43.
    Higgins JPT, Altman DG, Gotzsche PC, Juni P et al (2011) The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 343:d5928PubMedCrossRefPubMedCentralGoogle Scholar
  44. 44.
    Moher D, Liberati A, Tetzlaff J, Altman DG (2009) PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6:e1000097PubMedCrossRefPubMedCentralGoogle Scholar
  45. 45.
    DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–180PubMedCrossRefGoogle Scholar
  46. 46.
    Higgins JPT, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560PubMedCrossRefPubMedCentralGoogle Scholar
  47. 47.
    Easterbrook PJ, Berlin JA, Gopalan R, Matthews DR (1991) Publication bias in clinical research. Lancet 337:867–872PubMedCrossRefGoogle Scholar
  48. 48.
    Lim E, Ali Z, Ali A, Routledge T, Edmonds L, Altman DG, Large S (2007) Indirect comparison meta-analysis of aspirin therapy after coronary surgery. BMJ 327:1–5Google Scholar
  49. 49.
    Sattar N, Preiss D, Murray HM et al (2010) Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet 375:735–742PubMedCrossRefGoogle Scholar
  50. 50.
    Scheen AJ (2007) Antidiabetic agents in subjects with mild dysglycaemia: prevention or early treatment of type 2 diabetes? Diabetes Metab 33:3–12PubMedCrossRefGoogle Scholar
  51. 51.
    Buchwald H, Estok R, Fahrbach K, Banel D, Jensen MD, Pories WJ, Bantle JP, Sledge I (2009) Weight and type 2 diabetes after bariatric surgery: systematic review and meta-analysis. Am J Med 122(248–256):e5PubMedGoogle Scholar
  52. 52.
    Arterburn DE, Bogart A, Sherwood NE, Sidney S, Coleman KJ, Haneuse S, O’Connor PJ, Theis MK, Campos GM, McCulloch D, Selby J (2013) A multisite study of long-term remission and relapse of type 2 diabetes mellitus following gastric bypass. Obes Surg 23:93–102PubMedCrossRefGoogle Scholar
  53. 53.
    Diabetes Prevention Program Research Group (2003) Effects of withdrawal from metformin on the development of diabetes in the diabetes prevention program. Diabetes Care 26:977–980CrossRefGoogle Scholar
  54. 54.
    Pontiroli AE, Merlotti C, Veronelli A, Lombardi F (2013) Effect of weight loss on sympatho-vagal balance in subjects with grade-3 obesity: restrictive surgery versus hypocaloric diet. Acta Diabetol 50:843–850PubMedCrossRefGoogle Scholar
  55. 55.
    Folini L, Veronelli A, Benetti A, Pozzato C, Cappelletti M, Masci E, Micheletto G, Pontiroli AE (2014) Liver steatosis (LS) evaluated through chemical-shift magnetic resonance imaging liver enzymes in morbid obesity; effect of weight loss obtained with intragastric balloon gastric banding. Acta Diabetol 51(3):361–368PubMedCrossRefGoogle Scholar
  56. 56.
    Adams ST, Salhab M, Hussain ZI, Miller GV, Leveson SH (2013) Preoperatively determinable factors predictive of diabetes mellitus remission following Roux-en-Y gastric bypass: a review of the literature. Acta Diabetol 50:475–478PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2014

Authors and Affiliations

  • Claudia Merlotti
    • 1
  • Alberto Morabito
    • 2
  • Valerio Ceriani
    • 3
  • Antonio E. Pontiroli
    • 1
  1. 1.Cattedra di Medicina Interna and Cattedra di Statistica Medica e Biometria, Dipartimento di Scienze della SaluteUniversità degli Studi di MilanoMilanItaly
  2. 2.Dipartimento di Scienze Cliniche e di ComunitàUniversità degli Studi di MilanoMilanItaly
  3. 3.IRCCS MultimedicaMilanItaly

Personalised recommendations