Current Diabetes Reports

, 17:4 | Cite as

Medical Management of Diabesity: Do We Have Realistic Targets?

Pharmacologic Treatment of Type 2 Diabetes (HE Lebovitz and G Bahtiyar, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Pharmacologic Treatment of Type 2 Diabetes

Abstract

Purpose of Review

The global prevalence of “diabesity”—diabetes related to obesity—is increasing steadily over the past few decades because of the obesity epidemic. Although bariatric surgery is an effective treatment option for patients with diabesity, its limited availability, invasiveness, relatively high costs and the potential for surgical and postsurgical complications restrict its widespread use. Therefore, medical management is the only option for a majority of patients with diabesity. Diabetes control with several anti-diabetic agents, including insulin, causes weight gain with probability of worsening diabesity. Rational use of anti-diabetic medications with weight loss potential in varying combinations may help to address this key issue for long-term management of diabesity. There is no consensus on such an approach from different professional bodies like American Diabetes Association, European Association for Study of Diabetes, or International Diabetes Federation. We attempt to discuss the key issues and realistic targets for diabesity management in this paper.

Recent Findings

Rational use of anti-diabetic combinations can mitigate worsening of diabesity to some extent while managing patients.

Summary

Retrospective studies showed that combination therapy with glucagon-like peptide-1 (GLP-1) receptor agonists and sodium glucose co-transporter 2 (SGLT-2) inhibitors, when administered along with other anti-diabetic medications, offer the best therapeutic benefit in the medical management of diabesity. Different combinations of other anti-diabetic drugs with minimum weight gain potential were also found useful. Because of insufficient evidence based on prospective randomised controlled trials (RCTs), future research should focus on evolving the appropriate rational drug combinations for the medical management of diabesity.

Keywords

Diabesity Anti-diabetic medication Anti-diabetic drug combination Anti-obesity agents Management of diabesity 

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    • World Health Organization. 2015 Obesity and overweight. Geneva: World Health Organization. Available from: http://www.who.int/mediacentre/factsheets/fs311/en/. Assessed 30th March. Data from WHO that gives an idea about the magnitude of the problem.
  2. 2.
    • Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of childhood and adult obesity in the United States, 2011-2012. JAMA. 2014;311:806–14. A study to alert the clinicians on the alarming increase in obesity and consequent diabesity in adults CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    D’Adamo E, Caprio S. Type 2 diabetes in youth: epidemiology and pathophysiology. Diabetes Care. 2011;34(Suppl 2):S161–5.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    •• Sims EA, Danforth Jr E, Horton ES, Bray GA, Glennon JA, Salans LB. Endocrine and metabolic effects of experimental obesity in man. Recent Prog Horm Res. 1973;29:457–96. The first study that gave a clear interlink between obesity and T2DM PubMedGoogle Scholar
  5. 5.
    • Mingrone G, Panunzi S, De Gaetano A, Guidone C, Iaconelli A, Nanni G, et al. Bariatric-metabolic surgery versus conventional medical treatment in obese patients with type 2 diabetes: 5 year follow-up of an open-label, single-centre, randomised controlled trial. Lancet. 2015;386(9997):964–73. The first 5-year RCT showing the benefit of bariatric surgery in management of diabesity CrossRefPubMedGoogle Scholar
  6. 6.
    • Schauer PR, Bhatt DL, Kirwan JP, Wolski K, Brethauer SA, Navaneethan SD, Aminian A, Pothier CE, Kim ES, Nissen SE, Kashyap SR. STAMPEDE investigators. Bariatric surgery versus intensive medical therapy for diabetes—3-year outcomes. N Engl J Med. 2014;370:2002–13. The first well-designed RCT on the benefit of bariatric surgery in diabesity management CrossRefPubMedGoogle Scholar
  7. 7.
    • Paulus GF, de Vaan LE, Verdam FJ, Bouvy ND, Ambergen TA, van Heurn LW. Bariatric surgery in morbidly obese adolescents: a systematic review and meta-analysis. Obes Surg. 2015;25:860–78. A recent meta-analysis showing the benefits of gastric bypass procedures CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    •• Kahn SE, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature. 2006;444(7121):840–6. An important article showing the mechanisms of insulin resistance leading on to T2 DM CrossRefPubMedGoogle Scholar
  9. 9.
    Tzanetakou IP, Katsilambros NL, Benetos A, Mikhailidis DP, Perrea DN. Is obesity linked to aging?: adipose tissue and the role of telomeres. Ageing Res Rev. 2012;11:220–9.CrossRefPubMedGoogle Scholar
  10. 10.
    Chadt A, Scherneck S, Joost HG, Al-Hasani H. 2000-2014. Molecular links between obesity and diabetes: “diabesity”. In: De Groot LJ, Beck-Peccoz P, Chrousos G, Dungan K, Grossman A, Hershman JM, Koch C, McLachlan R, New M, Rebar R, Singer F, Vinik A, Weickert MO, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.Google Scholar
  11. 11.
    •• Locke AE, Kahali B, Berndt SI, Justice AE, Pers TH, Day FR, et al. Genetic studies of body mass index yield new insights for obesity biology. Nature. 2015;518(7538):197–206. An important study giving insights into the pathobiology of obesity CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    • Merlotti C, Morabito A, Pontiroli AE. Prevention of type 2 diabetes; a systematic review and meta-analysis of different intervention strategies. Diabetes Obes Metab. 2014;16:719–27. A study showing the benefits of different intervention for prevention of T2 DM CrossRefPubMedGoogle Scholar
  13. 13.
    Baillot A, Romain AJ, Boisvert-Vigneault K, Audet M, Baillargeon JP, Dionne IJ, Valiquette L, Chakra CN, Avignon A, Langlois MF. Effects of lifestyle interventions that include a physical activity component in class II and III obese individuals: a systematic review and meta-analysis. PLoS One. 2015;10:e0119017.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Terranova CO, Brakenridge CL, Lawler SP, Eakin EG, Reeves MM. Effectiveness of lifestyle-based weight loss interventions for adults with type 2 diabetes: a systematic review and meta-analysis. Diabetes Obes Metab. 2015;17:371–8.CrossRefPubMedGoogle Scholar
  15. 15.
    •• Franz MJ, Boucher JL, Rutten-Ramos S, Van Wormer JJ. Lifestyle weight-loss intervention outcomes in overweight and obese adults with type 2 diabetes: a systematic review and meta-analysis of randomized clinical trials. J Acad Nutr Diet. 2015;115:1447–63. A study of different RCTs on the management of diabesity through weight loss by lifestyle changes CrossRefPubMedGoogle Scholar
  16. 16.
    Miguelgorry PL, Hendricks EJ. Pharmacotherapy for obesity and changes in eating behavior: a patient and physician’s perspective. Adv Ther. 2016;33:1262–6.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    van Wyk HJ, Davis RE, Davies JS. A critical review of low-carbohydrate diets in people with type 2 diabetes. Diabet Med. 2016;33:148–57.CrossRefPubMedGoogle Scholar
  18. 18.
    Wang C, Mamza J, Idris I. Biphasic vs basal bolus insulin regimen in type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials. Diabet Med. 2015;32:585–94.CrossRefPubMedGoogle Scholar
  19. 19.
    Golay A. Metformin and body weight. Int J Obes. 2008;32:61–72.CrossRefGoogle Scholar
  20. 20.
    •• Domecq JP, Prutsky G, Leppin A, Sonbol MB, Altayar O, Undavalli C, et al. Clinical review: drugs commonly associated with weight change: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2015;100:363–70. An important study showing the effects of different drugs on body weight CrossRefPubMedGoogle Scholar
  21. 21.
    DeFronzo RA, Abdul-Ghani M. Type 2 diabetes can be prevented with early pharmacological intervention. Diabetes Care. 2011;34(Suppl 2):S202–9.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Hostalek U, Gwilt M, Hildemann S. Therapeutic use of metformin in prediabetes and diabetes prevention. Drugs. 2015;75:1071–94.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Naderpoor N, Shorakae S, de Courten B, Misso ML, Moran LJ, Teede HJ. Metformin and lifestyle modification in polycystic ovary syndrome: systematic review and meta-analysis. Hum Reprod Update. 2015;21:560–74.CrossRefPubMedGoogle Scholar
  24. 24.
    Kong W, Niu X, Zeng T, Lu M, Chen L. Impact of treatment with metformin on adipocytokines in patients with polycystic ovary syndrome: a meta-analysis. PLoS One. 2015;10:e0140565.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Kitwitee P, Limwattananon S, Limwattananon C, Waleekachonlert O, Ratanachotpanich T, Phimphilai M, Nguyen TV, Pongchaiyakul C. Metformin for the treatment of gestational diabetes: an updated meta-analysis. Diabetes Res Clin Pract. 2015;109:521–32.CrossRefPubMedGoogle Scholar
  26. 26.
    •• Jiang YF, Chen XY, Ding T, Wang XF, Zhu ZN, Su SW. Comparative efficacy and safety of OADs in management of GDM: network meta-analysis of randomized controlled trials. J Clin Endocrinol Metab. 2015;100:2071–80. A study on the role of metformin for gestational diabetes CrossRefPubMedGoogle Scholar
  27. 27.
    • Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, Charlton M, Sanyal AJ. The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology. 2012;55:2005–23. A clinical practice guideline helping physicians to manage NAFLD appropriately] CrossRefPubMedGoogle Scholar
  28. 28.
    Yu H, Yin L, Jiang X, Sun X, Wu J, Tian H, Gao X, He X. Effect of metformin on cancer risk and treatment outcome of prostate cancer: a meta-analysis of epidemiological observational studies. PLoS One. 2014;9:e116327.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Wu L, Zhu J, Prokop LJ, Murad MH. Pharmacologic therapy of diabetes and overall cancer risk and mortality: a meta-analysis of 265 studies. Sci Rep. 2015;5:10147.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Singh S, Khera R, Allen AM, Murad MH, Loomba R. Comparative effectiveness of pharmacological interventions for nonalcoholic steatohepatitis: a systematic review and network meta-analysis. Hepatology. 2015;62:1417–32.CrossRefPubMedGoogle Scholar
  31. 31.
    Tuccori M, Filion KB, Yin H, Yu OH, Platt RW, Azoulay L. Pioglitazone use and risk of bladder cancer: population based cohort study. BMJ. 2016;352:i1541.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Lecka-Czernik B. Bone loss in diabetes: use of antidiabetic thiazolidinediones and secondary osteoporosis. Curr Osteoporos Rep. 2010;8:178–84.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    •• Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JF, Nauck MA, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375(4):311–22. A recent clinical trial showing the cardiovascular mortality benefit of GLP-1 receptor agonists CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Pappachan JM, Raveendran AV, Sriraman R. Incretin manipulation in diabetes management. World J Diabetes. 2015;6:774–81.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Prasad-Reddy L, Isaacs D. A clinical review of GLP-1 receptor agonists: efficacy and safety in diabetes and beyond. Drugs Context. 2015;4:212283.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Pappachan JM. Incretin-based therapies and pancreatitis risk: myth or reality. Endocrine. 2015;48:360–2.CrossRefPubMedGoogle Scholar
  37. 37.
    Giorda CB, Sacerdote C, Nada E, Marafetti L, Baldi I, Gnavi R. Incretin-based therapies and acute pancreatitis risk: a systematic review and meta-analysis of observational studies. Endocrine. 2015;48:461–71.CrossRefPubMedGoogle Scholar
  38. 38.
    • Li L, Shen J, Bala MM, Busse JW, Ebrahim S, Vandvik PO, et al. Incretin treatment and risk of pancreatitis in patients with type 2 diabetes mellitus: systematic review and meta-analysis of randomised and non-randomised studies. BMJ. 2014;348:g2366. A meta-analysis that refuted the scare about the elevated pancreatitis risk associated with GLP-1 receptor agonists CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    • Pi-Sunyer X, Astrup A, Fujioka K, Greenway F, Halpern A, Krempf M, et al. A randomized, controlled trial of 3.0 mg of liraglutide in weight management. N Engl J Med. 2015;373:11–22. An RCT showing benefit of using liraglutide for obesity without diabetes CrossRefPubMedGoogle Scholar
  40. 40.
    Cai X, Han X, Luo Y, Ji L. Efficacy of dipeptidyl-peptidase-4 inhibitors and impact on β-cell function in Asian and Caucasian type 2 diabetes mellitus patients: a meta-analysis. J Diabetes. 2015;7:347–59.CrossRefPubMedGoogle Scholar
  41. 41.
    • Green JB, Bethel MA, Armstrong PW, Buse JB, Engel SS, Garg J, et al. Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2015;373:232–42. Clinical trial showing cardiovascular safety of sitagliptin CrossRefPubMedGoogle Scholar
  42. 42.
    Ou SM, Shih CJ, Chao PW, Chu H, Kuo SC, Lee YJ, et al. Effects on clinical outcomes of adding dipeptidyl peptidase-4 inhibitors versus sulfonylureas to metformin therapy in patients with type 2 diabetes mellitus. Ann Intern Med. 2015;163:663–72.CrossRefPubMedGoogle Scholar
  43. 43.
    Filion KB, Azoulay L, Platt RW, Dahl M, Dormuth CR, Clemens KK, et al. A multicenter observational study of incretin-based drugs and heart failure. N Engl J Med. 2016;374:1145–54.CrossRefPubMedGoogle Scholar
  44. 44.
    •• Li L, Li S, Deng K, Liu J, Vandvik PO, Zhao P, et al. Dipeptidyl peptidase-4 inhibitors and risk of heart failure in type 2 diabetes: systematic review and meta-analysis of randomised and observational studies. BMJ. 2016;352:i610. A systematic review compiling evidence for increased risk of hospitalization among patients treated with DPP-4 inhibitors CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    •• Vasilakou D, Karagiannis T, Athanasiadou E, Mainou M, Liakos A, Bekiari E, et al. Sodium-glucose cotransporter 2 inhibitors for type 2 diabetes: a systematic review and meta-analysis. Ann Intern Med. 2013;159:262–74. Article showing efficacy of different SGLT-2 inhibitors in the management of diabesity. CrossRefPubMedGoogle Scholar
  46. 46.
    Baker WL, Smyth LR, Riche DM, Bourret EM, Chamberlin KW, White WB. Effects of sodium-glucose co-transporter 2 inhibitors on blood pressure: a systematic review and meta-analysis. J Am Soc Hypertens. 2014;8:262–75. e9CrossRefPubMedGoogle Scholar
  47. 47.
    Sjöström CD, Hashemi M, Sugg J, Ptaszynska A, Johnsson E. Dapagliflozin-induced weight loss affects 24-week glycated haemoglobin and blood pressure levels. Diabetes Obes Metab. 2015;17:809–12.CrossRefPubMedGoogle Scholar
  48. 48.
    •• Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373:2117–28. The first clinical trial showing cardiovascular mortality benefit and weight loss effect of an antidiabetic medication CrossRefPubMedGoogle Scholar
  49. 49.
    Wanner C, Inzucchi SE, Lachin JM, Fitchett D, von Eynatten M, Mattheus M, et al. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med. 2016;375:323–34.CrossRefPubMedGoogle Scholar
  50. 50.
    • American Diabetes Association. (7) Approaches to glycemic treatment. Diabetes Care. 2015;38(Suppl):S41–8. An article discussing practical tips for glycaemic management in patients including those with diabesity CrossRefGoogle Scholar
  51. 51.
    Yanovski SZ, Yanovski JA. Long-term drug treatment for obesity: a systematic and clinical review. JAMA. 2014;311:74–86.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Plock N, Bax L, Lee D, DeManno D, Lahu G, Pfister M. Exploratory literature meta-analysis to characterize the relationship between early and longer term body weight loss for antiobesity compounds. J Clin Pharmacol. 2017;57:52–63.Google Scholar
  53. 53.
    Aldekhail NM, Logue J, McLoone P, Morrison DS. Effect of orlistat on glycaemic control in overweight and obese patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials. Obes Rev. 2015;16:1071–80.CrossRefPubMedGoogle Scholar
  54. 54.
    • Solomon TP, Knudsen SH, Karstoft K, Winding K, Holst JJ, Pedersen BK. Examining the effects of hyperglycemia on pancreatic endocrine function in humans: evidence for in vivo glucotoxicity. J Clin Endocrinol Metab. 2012;97:4682–91. An article looking at pancreatic glucotoxicity and its effects on diabetes control CrossRefPubMedGoogle Scholar
  55. 55.
    Campos C. Chronic hyperglycemia and glucose toxicity: pathology and clinical sequelae. Postgrad Med. 2012;124:90–7.CrossRefPubMedGoogle Scholar
  56. 56.
    Kaneto H, Matsuoka TA, Kimura T, Obata A, Shimoda M, Kamei S, Mune T, Kaku K. Appropriate therapy for type 2 diabetes mellitus in view of pancreatic β-cell glucose toxicity: “the earlier, the better”. J Diabetes. 2016;8:183–9.CrossRefPubMedGoogle Scholar
  57. 57.
    Vanhorebeek I, Ellger B, De Vos R, Boussemaere M, Debaveye Y, Perre SV, et al. Tissue-specific glucose toxicity induces mitochondrial damage in a burn injury model of critical illness. Crit Care Med. 2009;37:1355–64.CrossRefPubMedGoogle Scholar
  58. 58.
    Hanefeld M, Monnier L, Schnell O, Owens D. Early treatment with basal insulin glargine in people with type 2 diabetes: lessons from ORIGIN and other cardiovascular trials. Diabetes Ther. 2016;7:187–201.CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Liu SC, Tu YK, Chien MN, Chien KL. Effect of antidiabetic agents added to metformin on glycaemic control, hypoglycaemia and weight change in patients with type 2 diabetes: a network meta-analysis. Diabetes Obes Metab. 2012;14:810–20.CrossRefPubMedGoogle Scholar
  60. 60.
    McIntosh B, Cameron C, Singh SR, Yu C, Ahuja T, Welton NJ, Dahl M. Second-line therapy in patients with type 2 diabetes inadequately controlled with metformin monotherapy: a systematic review and mixed-treatment comparison meta-analysis. Open Med. 2011;5:e35–48.PubMedPubMedCentralGoogle Scholar
  61. 61.
    Lundby-Christensen L, Tarnow L, Boesgaard TW, Lund SS, Wiinberg N, Perrild H, et al. Metformin versus placebo in combination with insulin analogues in patients with type 2 diabetes mellitus—the randomised, blinded Copenhagen insulin and metformin therapy (CIMT) trial. BMJ Open. 2016;6:e008376.CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Phung OJ, Sobieraj DM, Engel SS, Rajpathak SN. Early combination therapy for the treatment of type 2 diabetes mellitus: systematic review and meta-analysis. Diabetes Obes Metab. 2014;16:410–7.CrossRefPubMedGoogle Scholar
  63. 63.
    Zhang F, Xiang H, Fan Y, Ganchuluun TA, Kong W, Ouyang Q, Sun J, Cao B, Jiang H, Nie S. The effects of sulfonylureas plus metformin on lipids, blood pressure, and adverse events in type 2 diabetes: a meta-analysis of randomized controlled trials. Endocrine. 2013;44:648–58.CrossRefPubMedGoogle Scholar
  64. 64.
    •• Qaseem A, Humphrey LL, Sweet DE, Starkey M, Shekelle P. Clinical guidelines Committee of the American College of physicians. Oral pharmacologic treatment of type 2 diabetes mellitus: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2012;156:756. An article looking at different combination regimens for appropriate management of T2 DM CrossRefGoogle Scholar
  65. 65.
    Mearns ES, Sobieraj DM, White CM, Saulsberry WJ, Kohn CG, Doleh Y, Zaccaro E, Coleman CI. Comparative efficacy and safety of antidiabetic drug regimens added to metformin monotherapy in patients with type 2 diabetes: a network meta-analysis. PLoS One. 2015;10:e0125879.CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Zhong X, Zhang T, Liu Y, Wei X, Zhang X, Qin Y, Jin Z, Chen Q, Ma X, Wang R, He J. Effects of three injectable antidiabetic agents on glycaemic control, weight change and drop-out in type 2 diabetes sub-optimally controlled with metformin and/or a sulfonylurea: a network meta-analysis. Diabetes Res Clin Pract. 2015;109:451–60.CrossRefPubMedGoogle Scholar
  67. 67.
    Dai X, Wang H, Jing Z, Fu P. The effect of a dual combination of noninsulin antidiabetic drugs on lipids: a systematic review and network meta-analysis. Curr Med Res Opin. 2014;30:1777–86.CrossRefPubMedGoogle Scholar
  68. 68.
    Shankar RR, Xu L, Golm GT, O’Neill EA, Goldstein BJ, Kaufman KD, Engel SS. A comparison of glycaemic effects of sitagliptin and sulfonylureas in elderly patients with type 2 diabetes mellitus. Int J Clin Pract. 2015;69:626–31.CrossRefPubMedGoogle Scholar
  69. 69.
    Esposito K, Chiodini P, Maiorino MI, Bellastella G, Capuano A, Giugliano D. Glycaemic durability with dipeptidyl peptidase-4 inhibitors in type 2 diabetes: a systematic review and meta-analysis of long-term randomised controlled trials. BMJ Open. 2014;4:e005442.CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Zhang Q, Dou J, Lu J. Combinational therapy with metformin and sodium-glucose cotransporter inhibitors in management of type 2 diabetes: systematic review and meta-analyses. Diabetes Res Clin Pract. 2014;105:313–21.CrossRefPubMedGoogle Scholar
  71. 71.
    Yang T, Lu M, Ma L, Zhou Y, Cui Y. Efficacy and tolerability of canagliflozin as add-on to metformin in the treatment of type 2 diabetes mellitus: a meta-analysis. Eur J Clin Pharmacol. 2015;71:1325–32.CrossRefPubMedGoogle Scholar
  72. 72.
    • Maruthur NM, Tseng E, Hutfless S, Wilson LM, Suarez-Cuervo C, Berger Z, Chu Y, Iyoha E, Segal JB, Bolen S. Diabetes medications as monotherapy or metformin-based combination therapy for type 2 diabetes: a systematic review and meta-analysis. Ann Intern Med. 2016;164:740–51. An important article looking at evidence base for rational antidiabetic combinations CrossRefPubMedGoogle Scholar
  73. 73.
    Pappachan JM, Antonio FA, Edavalath M, Mukherjee A. Non-alcoholic fatty liver disease: a diabetologist’s perspective. Endocrine. 2014;45:344–53.CrossRefPubMedGoogle Scholar
  74. 74.
    • Kawalec P, Mikrut A, Łopuch S. The safety of dipeptidyl peptidase-4 (DPP-4) inhibitors or sodium-glucose cotransporter 2 (SGLT-2) inhibitors added to metformin background therapy in patients with type 2 diabetes mellitus: a systematic review and meta-analysis. Diabetes Metab Res Rev. 2014;30:269–83. An article showing benefit of combination of DPP-4 inhibitors and SGLT-2 inhibitors in the management of diabesity Google Scholar
  75. 75.
    • Mearns ES, Saulsberry WJ, White CM, Kohn CG, Lemieux S, Sihabout A, Salamucha I, Coleman CI. Efficacy and safety of antihyperglycaemic drug regimens added to metformin and sulphonylurea therapy in type 2 diabetes: a network meta-analysis. Diabet Med. 2015;32:1530–40. An article that shows beneficial effect of adding an SGLT-2 inhibitor to other antidiabetic agents in managing diabesity CrossRefPubMedGoogle Scholar
  76. 76.
    Lozano-Ortega G, Goring S, Bennett HA, Bergenheim K, Sternhufvud C, Mukherjee J. Network meta-analysis of treatments for type 2 diabetes mellitus following failure with metformin plus sulfonylurea. Curr Med Res Opin. 2016;32:807–16.CrossRefPubMedGoogle Scholar
  77. 77.
    Saroka RM, Kane MP, Busch RS, Watsky J, Hamilton RA. SGLT-2 inhibitor therapy added to GLP-1 agonist therapy in The management of T2DM. Endocr Pract. 2015;21:1315–22. A retrospective study showing the benefit of add on therapy of SGLT-2 inhibitors with GLP-1 receptor agonists in patients with diabesity CrossRefPubMedGoogle Scholar
  78. 78.
    •• Deol H, Lekkakou L, Viswanath AK, Pappachan JM. Combination therapy with GLP-1 analogues and SGLT-2 inhibitors for the management of diabesity: the real world experience. Endocrine. 2017;55:173–8. A retrospective study showing remarkable benefit of adding an SGLT-2 inhibitor to GLP-1 receptor agonist in the medical management of diabesity CrossRefPubMedGoogle Scholar
  79. 79.
    •• Taylor SI, Blau JE, Rother KI. SGLT2 inhibitors may predispose to ketoacidosis. J Clin Endocrinol Metab. 2015;100:2849–52. An article that highlights the importance of exercising caution in the use of SGLT-2 inhibitors in clinical practice CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Smits MM, Tonneijck L, Muskiet MH, Kramer MH, Cahen DL, van Raalte DH. Gastrointestinal actions of glucagon-like peptide-1-based therapies: glycaemic control beyond the pancreas. Diabetes Obes Metab. 2016;18:224–35.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Department of Endocrinology and Diabetes, Royal Lancaster InfirmaryUniversity Hospitals of Morecambe NHS TrustLancasterUK
  2. 2.Department of Endocrinology and Diabetes, New Cross HospitalThe Royal Wolverhampton Hospitals NHS TrustWolverhamptonUK

Personalised recommendations