Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)

Melanie J Davies, David A D'Alessio, Judith Fradkin, Walter N Kernan, Chantal Mathieu, Geltrude Mingrone, Peter Rossing, Apostolos Tsapas, Deborah J Wexler, John B Buse, Melanie J Davies, David A D'Alessio, Judith Fradkin, Walter N Kernan, Chantal Mathieu, Geltrude Mingrone, Peter Rossing, Apostolos Tsapas, Deborah J Wexler, John B Buse

Abstract

The American Diabetes Association and the European Association for the Study of Diabetes convened a panel to update the prior position statements, published in 2012 and 2015, on the management of type 2 diabetes in adults. A systematic evaluation of the literature since 2014 informed new recommendations. These include additional focus on lifestyle management and diabetes self-management education and support. For those with obesity, efforts targeting weight loss, including lifestyle, medication, and surgical interventions, are recommended. With regards to medication management, for patients with clinical cardiovascular disease, a sodium-glucose cotransporter 2 (SGLT2) inhibitor or a glucagon-like peptide 1 (GLP-1) receptor agonist with proven cardiovascular benefit is recommended. For patients with chronic kidney disease or clinical heart failure and atherosclerotic cardiovascular disease, an SGLT2 inhibitor with proven benefit is recommended. GLP-1 receptor agonists are generally recommended as the first injectable medication.

© 2018 American Diabetes Association and European Association for the Study of Diabetes.

Figures

Figure 1
Figure 1
Decision cycle for patient-centered glycemic management in type 2 diabetes.
Figure 2
Figure 2
Glucose-lowering medication in type 2 diabetes: overall approach. CV, cardiovascular; DPP-4i, dipeptidyl peptidase 4 inhibitor; GLP-1 RA, glucagon-like peptide 1 receptor agonist; SGLT2i, SGLT2 inhibitor; SU, sulfonylurea.
Figure 3
Figure 3
Choosing glucose-lowering medication in those with established ASCVD, HF, and CKD. CV, cardiovascular; DPP-4i, dipeptidyl peptidase 4 inhibitor; GLP-1 RA, glucagon-like peptide 1 receptor agonist; SGLT2i, SGLT2 inhibitor; SU, sulfonylurea.
Figure 4
Figure 4
Choosing glucose-lowering medication if compelling need to minimize weight gain or promote weight loss. GLP-1 RA, glucagon-like peptide 1 receptor agonist; T2DM, type 2 diabetes; SGLT2i, SGLT2 inhibitor; SU, sulfonylurea.
Figure 5
Figure 5
Choosing glucose-lowering medication if compelling need to minimize hypoglycemia. DPP-4i, dipeptidyl peptidase 4 inhibitor; GLP-1 RA, glucagon-like peptide 1 receptor agonist; SGLT2i, SGLT2 inhibitor.
Figure 6
Figure 6
Choosing glucose-lowering medication if cost is a major issue. DPP-4i, dipeptidyl peptidase 4 inhibitor; SGLT2i, SGLT2 inhibitor; SU, sulfonylurea.
Figure 7
Figure 7
Intensifying to injectable therapies. FRC, fixed-ratio combination; GLP-1 RA, glucagon-like peptide 1 receptor agonist; FBG, fasting blood glucose; FPG, fasting plasma glucose; max, maximum; PPG, postprandial glucose.
Figure 8
Figure 8
Considering oral therapy in combination with injectable therapies. DKA, diabetic ketoacidosis; DPP-4i, dipeptidyl peptidase 4 inhibitor; GLP-1 RA, glucagon-like peptide 1 receptor agonist; SGLT2i, SGLT2 inhibitor; SU, sulfonylurea.

References

    1. Rodriguez-Gutierrez R, Gionfriddo MR, Ospina NS, et al. . Shared decision making in endocrinology: present and future directions. Lancet Diabetes Endocrinol 2016;4:706–716
    1. American Diabetes Association 6. Glycemic targets: Standards of Medical Care in Diabetes—2018. Diabetes Care 2018;41(Suppl. 1):S55–S64
    1. American Diabetes Association 8. Pharmacologic approaches to glycemic treatment: Standards of Medical Care in Diabetes—2018. Diabetes Care 2018;41(Suppl. 1):S73–S85
    1. Inzucchi SE, Bergenstal RM, Buse JB, et al. .; Position Statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) . Management of hyperglycaemia in type 2 diabetes a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia 2012;55:1577–1596
    1. Inzucchi SE, Bergenstal RM, Buse JB, et al. . Management of hyperglycaemia in type 2 diabetes, 2015: a patient-centred approach. Update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia 2015;58:429–442
    1. Riddle MC, Gerstein HC, Holman RR, et al. . A1C targets should be personalized to maximize benefits while limiting risks. Diabetes Care 2018;41:1121–1124
    1. American Diabetes Association 9. Cardiovascular disease and risk management: Standards of Medical Care in Diabetes—2018. Diabetes Care 2018;41(Suppl. 1):S86–S104
    1. Gæde P, Oellgaard J, Carstensen B, et al. . Years of life gained by multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: 21 years follow-up on the Steno-2 randomised trial. Diabetologia 2016;59:2298–2307
    1. Khunti K, Kosiborod M, Ray KK. Legacy benefits of blood glucose, blood pressure and lipid control in individuals with diabetes and cardiovascular disease: time to overcome multifactorial therapeutic inertia? Diabetes Obes Metab 2018;20:1337–1341
    1. Gregg EW, Sattar N, Ali MK. The changing face of diabetes complications. Lancet Diabetes Endocrinol 2016;4:537–547
    1. Little RR, Rohlfing CL, Sacks DB. Status of HbA1c measurement and goals for improvement: from chaos to order for improving diabetes care. Clin Chem 2011;57:204–214
    1. American Diabetes Association 2. Classification and diagnosis of diabetes: Standards of Medical Care in Diabetes—2018. Diabetes Care 2018;41(Suppl. 1):S13–S27
    1. Mannucci E, Antenore A, Giorgino F, Scavini M. Effects of structured versus unstructured self-monitoring of blood glucose on glucose control in patients with non-insulin-treated type 2 diabetes: a meta-analysis of randomized controlled trials. J Diabetes Sci Technol 2018;12:183–189
    1. Young LA, Buse JB, Weaver MA, et al. .; Monitor Trial Group . Glucose self-monitoring in non–insulin-treated patients with type 2 diabetes in primary care settings: a randomized trial. JAMA Intern Med 2017;177:920–929
    1. Anjana RM, Kesavadev J, Neeta D, et al. . A multicenter real-life study on the effect of flash glucose monitoring on glycemic control in patients with type 1 and type 2 diabetes. Diabetes Technol Ther 2017;19:533–540
    1. American Diabetes Association 3. Comprehensive medical evaluation and assessment of comorbidities: Standards of Medical Care in Diabetes—2018. Diabetes Care 2018;41(Suppl. 1):S28–S37
    1. Kunneman M, Montori VM, Castaneda-Guarderas A, Hess EP. What is shared decision making? (and what it is not). Acad Emerg Med 2016;23:1320–1324
    1. Breslin M, Mullan RJ, Montori VM. The design of a decision aid about diabetes medications for use during the consultation with patients with type 2 diabetes. Patient Educ Couns 2008;73:465–472
    1. Mullan RJ, Montori VM, Shah ND, et al. . The diabetes mellitus medication choice decision aid: a randomized trial. Arch Intern Med 2009;169:1560–1568
    1. Stacey D, Légaré F, Lewis K, et al. . Decision aids for people facing health treatment or screening decisions. Cochrane Database Syst Rev 2017;4:CD001431.
    1. American Diabetes Association 4. Lifestyle management: Standards of Medical Care in Diabetes—2018. Diabetes Care 2018;41(Suppl. 1):S38–S50
    1. Powers MA, Bardsley J, Cypress M, et al. . Diabetes self-management education and support in type 2 diabetes: a joint position statement of the American Diabetes Association, the American Association of Diabetes Educators, and the Academy of Nutrition and Dietetics. Diabetes Care 2015;38:1372–1382
    1. Department of Health Diabetes UK. Structured patient education in diabetes: report from the Patient Education Working Group. Structured patient education in diabetes: report from the Patient Education Working Group, 2005. Available from . Accessed 29 August 2018.
    1. National Institute for Health and Clinical Excellence Quality Standard for Diabetes in Adults, Statements 2 and 3, 2011. Available from . Accessed 29 August 2018.
    1. Beck J, Greenwood DA, Blanton L, et al. .; 2017 Standards Revision Task Force . 2017 National standards for diabetes self-management education and support. Diabetes Educ 2017;43:449–464
    1. Chrvala CA, Sherr D, Lipman RD. Diabetes self-management education for adults with type 2 diabetes mellitus: a systematic review of the effect on glycemic control. Patient Educ Couns 2016;99:926–943
    1. Pillay J, Armstrong MJ, Butalia S, et al. . Behavioral programs for type 2 diabetes mellitus: a systematic review and network meta-analysis. Ann Intern Med 2015;163:848–860
    1. Zhao F-F, Suhonen R, Koskinen S, Leino-Kilpi H. Theory-based self-management educational interventions on patients with type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials. J Adv Nurs 2017;73:812–833
    1. Odgers-Jewell K, Ball LE, Kelly JT, Isenring EA, Reidlinger DP, Thomas R. Effectiveness of group-based self-management education for individuals with type 2 diabetes: a systematic review with meta-analyses and meta-regression. Diabet Med 2017;34:1027–1039
    1. He X, Li J, Wang B, et al. . Diabetes self-management education reduces risk of all-cause mortality in type 2 diabetes patients: a systematic review and meta-analysis. Endocrine 2017;55:712–731
    1. Chatterjee S, Davies MJ, Heller S, Speight J, Snoek FJ, Khunti K. Diabetes structured self-management education programmes: a narrative review and current innovations. Lancet Diabetes Endocrinol 2018;6:130–142
    1. Egede LE, Gebregziabher M, Echols C, Lynch CP. Longitudinal effects of medication nonadherence on glycemic control. Ann Pharmacother 2014;48:562–570
    1. Huber CA, Reich O. Medication adherence in patients with diabetes mellitus: does physician drug dispensing enhance quality of care? Evidence from a large health claims database in Switzerland. Patient Prefer Adherence 2016;10:1803–1809
    1. Iglay K, Cartier SE, Rosen VM, et al. . Meta-analysis of studies examining medication adherence, persistence, and discontinuation of oral antihyperglycemic agents in type 2 diabetes. Curr Med Res Opin 2015;31:1283–1296
    1. McGovern A, Tippu Z, Hinton W, Munro N, Whyte M, de Lusignan S. Systematic review of adherence rates by medication class in type 2 diabetes: a study protocol. BMJ Open 2016;6:e010469
    1. Khunti K, Seidu S, Kunutsor S, Davies M. Association between adherence to pharmacotherapy and outcomes in type 2 diabetes: a meta-analysis. Diabetes Care 2017;40:1588–1596
    1. Polonsky WH, Henry RR. Poor medication adherence in type 2 diabetes: recognizing the scope of the problem and its key contributors. Patient Prefer Adherence 2016;10:1299–1307
    1. McGovern A, Tippu Z, Hinton W, Munro N, Whyte M, de Lusignan S. Comparison of medication adherence and persistence in type 2 diabetes: a systematic review and meta-analysis. Diabetes Obes Metab 2018;20:1040–1043
    1. Lasalvia P, Barahona-Correa JE, Romero-Alvernia DM, et al. . Pen devices for insulin self-administration compared with needle and vial: systematic review of the literature and meta-analysis. J Diabetes Sci Technol 2016;10:959–966
    1. Khunti K, Davies MJ. Clinical inertia-time to reappraise the terminology? Prim Care Diabetes 2017;11:105–106
    1. Furler J, O’Neal D, Speight J, et al. . Supporting insulin initiation in type 2 diabetes in primary care: results of the Stepping Up pragmatic cluster randomised controlled clinical trial. BMJ 2017;356:j783.
    1. Manski-Nankervis J-A, Furler J, O’Neal D, Ginnivan L, Thuraisingam S, Blackberry I. Overcoming clinical inertia in insulin initiation in primary care for patients with type 2 diabetes: 24-month follow-up of the Stepping Up cluster randomised controlled trial. Prim Care Diabetes 2017;11:474–481
    1. Tabesh M, Magliano DJ, Koye DN, Shaw JE. The effect of nurse prescribers on glycaemic control in type 2 diabetes: a systematic review and meta-analysis. Int J Nurs Stud 2018;78:37–43
    1. Murphy ME, Byrne M, Galvin R, Boland F, Fahey T, Smith SM. Improving risk factor management for patients with poorly controlled type 2 diabetes: a systematic review of healthcare interventions in primary care and community settings. BMJ Open 2017;7:e015135
    1. American Diabetes Association 1. Improving care and promoting health in populations: Standards of Medical Care in Diabetes—2018. Diabetes Care 2018;41(Suppl. 1):S7–S12
    1. Cefalu WT, Kaul S, Gerstein HC, et al. . Cardiovascular outcomes trials in type 2 diabetes: where do we go from here? Reflections from a Diabetes Care Editors’ Expert Forum. Diabetes Care 2018;41:14–31
    1. Marso SP, Daniels GH, Brown-Frandsen K, et al. .; LEADER Steering Committee; LEADER Trial Investigators . Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2016;375:311–322
    1. Marso SP, Bain SC, Consoli A, et al. .; SUSTAIN-6 Investigators . Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med 2016;375:1834–1844
    1. Holman RR, Bethel MA, Mentz RJ, et al. .; EXSCEL Study Group . Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes. N Engl J Med 2017;377:1228–1239
    1. Pfeffer MA, Claggett B, Diaz R, et al. .; ELIXA Investigators . Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N Engl J Med 2015;373:2247–2257
    1. Zinman B, Wanner C, Lachin JM, et al. .; EMPA-REG OUTCOME Investigators . Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015;373:2117–2128
    1. Neal B, Perkovic V, Mahaffey KW, et al. .; CANVAS Program Collaborative Group . Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med 2017;377:644–657
    1. Lehrke M, Marx N. Diabetes mellitus and heart failure. Am J Med 2017;130(6S):S40–S50
    1. Fitchett D, Zinman B, Wanner C, et al. .; EMPA-REG OUTCOME® trial investigators . Heart failure outcomes with empagliflozin in patients with type 2 diabetes at high cardiovascular risk: results of the EMPA-REG OUTCOME® trial. Eur Heart J 2016;37:1526–1534
    1. Rådholm K, Figtree G, Perkovic V, et al. . Canagliflozin and heart failure in type 2 diabetes mellitus: results from the CANVAS Program. Circulation 2018;138:458–469
    1. Margulies KB, Hernandez AF, Redfield MM, et al. .; NHLBI Heart Failure Clinical Research Network . Effects of liraglutide on clinical stability among patients with advanced heart failure and reduced ejection fraction: a randomized clinical trial. JAMA 2016;316:500–508
    1. Jorsal A, Kistorp C, Holmager P, et al. . Effect of liraglutide, a glucagon-like peptide-1 analogue, on left ventricular function in stable chronic heart failure patients with and without diabetes (LIVE)-a multicentre, double-blind, randomised, placebo-controlled trial. Eur J Heart Fail 2017;19:69–77
    1. Scirica BM, Bhatt DL, Braunwald E, et al. .; SAVOR-TIMI 53 Steering Committee and Investigators . Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med 2013;369:1317–1326
    1. White WB, Cannon CP, Heller SR, et al. .; EXAMINE Investigators . Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med 2013;369:1327–1335
    1. Green JB, Bethel MA, Armstrong PW, et al. .; TECOS Study Group . Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N Engl J Med 2015;373:232–242
    1. Wanner C, Inzucchi SE, Lachin JM, et al. .; EMPA-REG OUTCOME Investigators . Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med 2016;375:323–334
    1. Jardine MJ, Mahaffey KW, Neal B, et al. .; CREDENCE study investigators . The Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study rationale, design, and baseline characteristics. Am J Nephrol 2017;46:462–472
    1. Mann JFE, Ørsted DD, Brown-Frandsen K, et al. .; LEADER Steering Committee and Investigators . Liraglutide and renal outcomes in type 2 diabetes. N Engl J Med 2017;377:839–848
    1. Deacon CF. A review of dipeptidyl peptidase-4 inhibitors. Hot topics from randomized controlled trials. Diabetes Obes Metab 2018;20(Suppl. 1):34–46
    1. American Diabetes Association 7. Obesity management for the treatment of type 2 diabetes: Standards of Medical Care in Diabetes—2018. Diabetes Care 2018;41(Suppl. 1):S65–S72
    1. Shai I, Schwarzfuchs D, Henkin Y, et al. .; Dietary Intervention Randomized Controlled Trial (DIRECT) Group . Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet. N Engl J Med 2008;359:229–241
    1. Esposito K, Maiorino MI, Ciotola M, et al. . Effects of a Mediterranean-style diet on the need for antihyperglycemic drug therapy in patients with newly diagnosed type 2 diabetes: a randomized trial. Ann Intern Med 2009;151:306–314
    1. Esposito K, Maiorino MI, Petrizzo M, Bellastella G, Giugliano D. The effects of a Mediterranean diet on the need for diabetes drugs and remission of newly diagnosed type 2 diabetes: follow-up of a randomized trial. Diabetes Care 2014;37:1824–1830
    1. Huo R, Du T, Xu Y, et al. . Effects of Mediterranean-style diet on glycemic control, weight loss and cardiovascular risk factors among type 2 diabetes individuals: a meta-analysis. Eur J Clin Nutr 2015;69:1200–1208
    1. Snorgaard O, Poulsen GM, Andersen HK, Astrup A. Systematic review and meta-analysis of dietary carbohydrate restriction in patients with type 2 diabetes. BMJ Open Diabetes Res Care 2017;5:e000354
    1. Ajala O, English P, Pinkney J. Systematic review and meta-analysis of different dietary approaches to the management of type 2 diabetes. Am J Clin Nutr 2013;97:505–516
    1. Azadbakht L, Fard NRP, Karimi M, et al. . Effects of the Dietary Approaches to Stop Hypertension (DASH) eating plan on cardiovascular risks among type 2 diabetic patients: a randomized crossover clinical trial. Diabetes Care 2011;34:55–57
    1. Sainsbury E, Kizirian NV, Partridge SR, Gill T, Colagiuri S, Gibson AA. Effect of dietary carbohydrate restriction on glycemic control in adults with diabetes: a systematic review and meta-analysis. Diabetes Res Clin Pract 2018;139:239–252
    1. Yokoyama Y, Barnard ND, Levin SM, Watanabe M. Vegetarian diets and glycemic control in diabetes: a systematic review and meta-analysis. Cardiovasc Diagn Ther 2014;4:373–382
    1. Lean ME, Leslie WS, Barnes AC, et al. . Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. Lancet 2018;391:541–551
    1. Wing RR, Bolin P, Brancati FL, et al. .; Look AHEAD Research Group . Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. N Engl J Med 2013;369:145–154
    1. O’Neil PM, Miller-Kovach K, Tuerk PW, et al. . Randomized controlled trial of a nationally available weight control program tailored for adults with type 2 diabetes. Obesity (Silver Spring) 2016;24:2269–2277
    1. Jebb SA, Ahern AL, Olson AD, et al. . Primary care referral to a commercial provider for weight loss treatment versus standard care: a randomised controlled trial. Lancet 2011;378:1485–1492
    1. Leblanc ES, O’Connor E, Whitlock EP, Patnode CD, Kapka T. Effectiveness of primary care-relevant treatments for obesity in adults: a systematic evidence review for the U.S. Preventive Services Task Force. Ann Intern Med 2011;155:434–447
    1. Delahanty LM, Dalton KM, Porneala B, et al. . Improving diabetes outcomes through lifestyle change – a randomized controlled trial. Obesity (Silver Spring) 2015;23:1792–1799
    1. Boulé NG, Haddad E, Kenny GP, Wells GA, Sigal RJ. Effects of exercise on glycemic control and body mass in type 2 diabetes mellitus: a meta-analysis of controlled clinical trials. JAMA 2001;286:1218–1227
    1. Chudyk A, Petrella RJ. Effects of exercise on cardiovascular risk factors in type 2 diabetes: a meta-analysis. Diabetes Care 2011;34:1228–1237
    1. Yang Z, Scott CA, Mao C, Tang J, Farmer AJ. Resistance exercise versus aerobic exercise for type 2 diabetes: a systematic review and meta-analysis. Sports Med 2014;44:487–499
    1. Balducci S, Zanuso S, Nicolucci A, et al. .; Italian Diabetes Exercise Study (IDES) Investigators . Effect of an intensive exercise intervention strategy on modifiable cardiovascular risk factors in subjects with type 2 diabetes mellitus: a randomized controlled trial: the Italian Diabetes and Exercise Study (IDES). Arch Intern Med 2010;170:1794–1803
    1. Schwingshackl L, Missbach B, Dias S, König J, Hoffmann G. Impact of different training modalities on glycaemic control and blood lipids in patients with type 2 diabetes: a systematic review and network meta-analysis. Diabetologia 2014;57:1789–1797
    1. Qiu S, Cai X, Schumann U, Velders M, Sun Z, Steinacker JM. Impact of walking on glycemic control and other cardiovascular risk factors in type 2 diabetes: a meta-analysis. PLoS One 2014;9:e109767.
    1. Rees JL, Johnson ST, Boulé NG. Aquatic exercise for adults with type 2 diabetes: a meta-analysis. Acta Diabetol 2017;54:895–904
    1. Pai L-W, Li T-C, Hwu Y-J, Chang SC, Chen LL, Chang PY. The effectiveness of regular leisure-time physical activities on long-term glycemic control in people with type 2 diabetes: a systematic review and meta-analysis. Diabetes Res Clin Pract 2016;113:77–85
    1. Lee MS, Jun JH, Lim H-J, Lim H-S. A systematic review and meta-analysis of tai chi for treating type 2 diabetes. Maturitas 2015;80:14–23
    1. Cui J, Yan J-H, Yan L-M, Pan L, Le JJ, Guo YZ. Effects of yoga in adults with type 2 diabetes mellitus: a meta-analysis. J Diabetes Investig 2017;8:201–209
    1. Qiu S, Cai X, Chen X, Yang B, Sun Z. Step counter use in type 2 diabetes: a meta-analysis of randomized controlled trials. BMC Med 2014;12:36.
    1. Franz MJ, Boucher JL, Rutten-Ramos S, VanWormer 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;115:1447–1463
    1. Aggarwal N, Singla A, Mathieu C, et al. . Metformin extended-release versus immediate-release: an international, randomized, double-blind, head-to-head trial in pharmacotherapy-naïve patients with type 2 diabetes. Diabetes Obes Metab 2018;20:463–467
    1. Garber AJ, Duncan TG, Goodman AM, Mills DJ, Rohlf JL. Efficacy of metformin in type II diabetes: results of a double-blind, placebo-controlled, dose-response trial. Am J Med 1997;103:491–497
    1. Inzucchi SE, Lipska KJ, Mayo H, Bailey CJ, McGuire DK. Metformin in patients with type 2 diabetes and kidney disease: a systematic review. JAMA 2014;312:2668–2675
    1. Lalau J-D, Kajbaf F, Bennis Y, Hurtel-Lemaire AS, Belpaire F, De Broe ME. Metformin treatment in patients with type 2 diabetes and chronic kidney disease stages 3A, 3B, or 4. Diabetes Care 2018;41:547–553
    1. Imam TH. Changes in metformin use in chronic kidney disease. Clin Kidney J 2017;10:301–304
    1. UK Prospective Diabetes Study (UKPDS) Group Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998;352:854–865
    1. Griffin SJ, Leaver JK, Irving GJ. Impact of metformin on cardiovascular disease: a meta-analysis of randomised trials among people with type 2 diabetes. Diabetologia 2017;60:1620–1629
    1. Maruthur NM, Tseng E, Hutfless S, et al. . Diabetes medications as monotherapy or metformin-based combination therapy for type 2 diabetes: a systematic review and meta-analysis. Ann Intern Med 2016;164:740–751
    1. Aroda VR, Edelstein SL, Goldberg RB, et al. .; Diabetes Prevention Program Research Group . Long-term metformin use and vitamin B12 deficiency in the Diabetes Prevention Program Outcomes Study. J Clin Endocrinol Metab 2016;101:1754–1761
    1. Zhang X-L, Zhu Q-Q, Chen Y-H, et al. . Cardiovascular safety, long-term noncardiovascular safety, and efficacy of sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes mellitus: a systemic review and meta-analysis with trial sequential analysis. J Am Heart Assoc 2018;7:e007165.
    1. Storgaard H, Gluud LL, Bennett C, et al. . Benefits and harms of sodium-glucose co-transporter 2 inhibitors in patients with type 2 diabetes: a systematic review and meta-analysis. PLoS One 2016;11:e0166125.
    1. Li D, Wang T, Shen S, Fang Z, Dong Y, Tang H. Urinary tract and genital infections in patients with type 2 diabetes treated with sodium-glucose co-transporter 2 inhibitors: a meta-analysis of randomized controlled trials. Diabetes Obes Metab 2017;19:348–355
    1. Jabbour S, Seufert J, Scheen A, Bailey CJ, Karup C, Langkilde AM. Dapagliflozin in patients with type 2 diabetes mellitus: a pooled analysis of safety data from phase IIb/III clinical trials. Diabetes Obes Metab 2018;20:620–628
    1. Tang H, Li D, Wang T, Zhai S, Song Y. Effect of sodium-glucose cotransporter 2 inhibitors on diabetic ketoacidosis among patients with type 2 diabetes: a meta-analysis of randomized controlled trials. Diabetes Care 2016;39:e123–e124
    1. Thrasher J. Pharmacologic management of type 2 diabetes mellitus: available therapies. Am J Med 2017;130(6S):S4–S17
    1. Karagiannis T, Liakos A, Bekiari E, et al. . Efficacy and safety of once-weekly glucagon-like peptide 1 receptor agonists for the management of type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials. Diabetes Obes Metab 2015;17:1065–1074
    1. Zaccardi F, Htike ZZ, Webb DR, Khunti K, Davies MJ. Benefits and harms of once-weekly glucagon-like peptide-1 receptor agonist treatments: a systematic review and network meta-analysis. Ann Intern Med 2016;164:102–113
    1. Htike ZZ, Zaccardi F, Papamargaritis D, Webb DR, Khunti K, Davies MJ. Efficacy and safety of glucagon-like peptide-1 receptor agonists in type 2 diabetes: a systematic review and mixed-treatment comparison analysis. Diabetes Obes Metab 2017;19:524–536
    1. Sorli C, Harashima S-I, Tsoukas GM, et al. . Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in patients with type 2 diabetes (SUSTAIN 1): a double-blind, randomised, placebo-controlled, parallel-group, multinational, multicentre phase 3a trial. Lancet Diabetes Endocrinol 2017;5:251–260
    1. Pratley RE, Aroda VR, Lingvay I, et al. .; SUSTAIN 7 investigators . Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7): a randomised, open-label, phase 3b trial. Lancet Diabetes Endocrinol 2018;6:275–286
    1. Dungan KM, Povedano ST, Forst T, et al. . Once-weekly dulaglutide versus once-daily liraglutide in metformin-treated patients with type 2 diabetes (AWARD-6): a randomised, open-label, phase 3, non-inferiority trial. Lancet 2014;384:1349–1357
    1. Buse JB, Nauck M, Forst T, et al. . Exenatide once weekly versus liraglutide once daily in patients with type 2 diabetes (DURATION-6): a randomised, open-label study. Lancet 2013;381:117–124
    1. Buse JB, Rosenstock J, Sesti G, et al. .; LEAD-6 Study Group . Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6). Lancet 2009;374:39–47
    1. Drucker DJ, Buse JB, Taylor K, et al. .; DURATION-1 Study Group . Exenatide once weekly versus twice daily for the treatment of type 2 diabetes: a randomised, open-label, non-inferiority study. Lancet 2008;372:1240–1250
    1. Andreadis P, Karagiannis T, Malandris K, et al. . Semaglutide for type 2 diabetes mellitus: a systematic review and meta-analysis. Diabetes Obes Metab 2018;20:2255–2263
    1. Li Z, Zhang Y, Quan X, et al. . Efficacy and acceptability of glycemic control of glucagon-like peptide-1 receptor agonists among type 2 diabetes: a systematic review and network meta-analysis. PLoS One 2016;11:e0154206.
    1. Storgaard H, Cold F, Gluud LL, Vilsbøll T, Knop FK. Glucagon-like peptide-1 receptor agonists and risk of acute pancreatitis in patients with type 2 diabetes. Diabetes Obes Metab 2017;19:906–908
    1. Monami M, Nreu B, Scatena A, et al. . Safety issues with glucagon-like peptide-1 receptor agonists (pancreatitis, pancreatic cancer and cholelithiasis): data from randomized controlled trials. Diabetes Obes Metab 2017;19:1233–1241
    1. 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
    1. Aroda VR, Henry RR, Han J, et al. . Efficacy of GLP-1 receptor agonists and DPP-4 inhibitors: meta-analysis and systematic review. Clin Ther 2012;34:1247–1258.e22
    1. Wu S, Chai S, Yang J, et al. . Gastrointestinal adverse events of dipeptidyl peptidase 4 inhibitors in type 2 diabetes: a systematic review and network meta-analysis. Clin Ther 2017;39:1780–1789.e33
    1. Salvo F, Moore N, Arnaud M, et al. . Addition of dipeptidyl peptidase-4 inhibitors to sulphonylureas and risk of hypoglycaemia: systematic review and meta-analysis. BMJ 2016;353:i2231.
    1. Tkáč I, Raz I. Combined analysis of three large interventional trials with gliptins indicates increased incidence of acute pancreatitis in patients with type 2 diabetes. Diabetes Care 2017;40:284–286
    1. Mascolo A, Rafaniello C, Sportiello L, et al. . Dipeptidyl peptidase (DPP)-4 inhibitor-induced arthritis/arthralgia: a review of clinical cases. Drug Saf 2016;39:401–407
    1. Nauck MA, Meier JJ, Cavender MA, Abd El Aziz M, Drucker DJ. Cardiovascular actions and clinical outcomes with glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors. Circulation 2017;136:849–870
    1. Li L, Li S, Deng K, 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.
    1. Aronoff S, Rosenblatt S, Braithwaite S, Egan JW, Mathisen AL, Schneider RL. Pioglitazone hydrochloride monotherapy improves glycemic control in the treatment of patients with type 2 diabetes: a 6-month randomized placebo-controlled dose-response study. The Pioglitazone 001 Study Group. Diabetes Care 2000;23:1605–1611
    1. Einhorn D, Rendell M, Rosenzweig J, Egan JW, Mathisen AL, Schneider RL. Pioglitazone hydrochloride in combination with metformin in the treatment of type 2 diabetes mellitus: a randomized, placebo-controlled study. The Pioglitazone 027 Study Group. Clin Ther 2000;22:1395–1409
    1. Yki-Järvinen H. Thiazolidinediones. N Engl J Med 2004;351:1106–1118
    1. Kernan WN, Viscoli CM, Furie KL, et al. .; IRIS Trial Investigators . Pioglitazone after ischemic stroke or transient ischemic attack. N Engl J Med 2016;374:1321–1331
    1. Hanefeld M, Marx N, Pfützner A, et al. . Anti-inflammatory effects of pioglitazone and/or simvastatin in high cardiovascular risk patients with elevated high sensitivity C-reactive protein: the PIOSTAT Study. J Am Coll Cardiol 2007;49:290–297
    1. Saremi A, Schwenke DC, Buchanan TA, et al. . Pioglitazone slows progression of atherosclerosis in prediabetes independent of changes in cardiovascular risk factors. Arterioscler Thromb Vasc Biol 2013;33:393–399
    1. Nissen SE, Nicholls SJ, Wolski K, et al. .; PERISCOPE Investigators . Comparison of pioglitazone vs glimepiride on progression of coronary atherosclerosis in patients with type 2 diabetes: the PERISCOPE randomized controlled trial. JAMA 2008;299:1561–1573
    1. Dormandy JA, Charbonnel B, Eckland DJA, et al. .; PROactive Investigators . Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet 2005;366:1279–1289
    1. Bach RG, Brooks MM, Lombardero M, et al. .; BARI 2D Investigators . Rosiglitazone and outcomes for patients with diabetes mellitus and coronary artery disease in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial. Circulation 2013;128:785–794
    1. Mahaffey KW, Hafley G, Dickerson S, et al. . Results of a reevaluation of cardiovascular outcomes in the RECORD trial. Am Heart J 2013;166:240–249.e1
    1. Cusi K, Orsak B, Bril F, et al. . Long-term pioglitazone treatment for patients with nonalcoholic steatohepatitis and prediabetes or type 2 diabetes mellitus: a randomized trial. Ann Intern Med 2016;165:305–315
    1. Kahn SE, Haffner SM, Heise MA, et al. .; ADOPT Study Group . Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med 2006;355:2427–2443
    1. Home PD, Pocock SJ, Beck-Nielsen H, et al. .; RECORD Study Team . Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial. Lancet 2009;373:2125–2135 [Lond Engl]
    1. Hanefeld M, Brunetti P, Schernthaner GH, Matthews DR, Charbonnel BH; QUARTET Study Group . One-year glycemic control with a sulfonylurea plus pioglitazone versus a sulfonylurea plus metformin in patients with type 2 diabetes. Diabetes Care 2004;27:141–147
    1. Viscoli CM, Inzucchi SE, Young LH, et al. .; IRIS Trial Investigators . Pioglitazone and risk for bone fracture: safety data from a randomized clinical trial. J Clin Endocrinol Metab 2017;102:914–922
    1. Kahn SE, Zinman B, Lachin JM, et al. .; Diabetes Outcome Progression Trial (ADOPT) Study Group . Rosiglitazone-associated fractures in type 2 diabetes: an analysis from A Diabetes Outcome Progression Trial (ADOPT). Diabetes Care 2008;31:845–851
    1. Lewis JD, Habel LA, Quesenberry CP, et al. . Pioglitazone use and risk of bladder cancer and other common cancers in persons with diabetes. JAMA 2015;314:265–277
    1. Hirst JA, Farmer AJ, Dyar A, Lung TW, Stevens RJ. Estimating the effect of sulfonylurea on HbA1c in diabetes: a systematic review and meta-analysis. Diabetologia 2013;56:973–984
    1. UK Prospective Diabetes Study (UKPDS) Group Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998;352:837–853
    1. Patel A, MacMahon S, Chalmers J, et al. .; ADVANCE Collaborative Group . Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 2008;358:2560–2572
    1. Monami M, Dicembrini I, Kundisova L, Zannoni S, Nreu B, Mannucci E. A meta-analysis of the hypoglycaemic risk in randomized controlled trials with sulphonylureas in patients with type 2 diabetes. Diabetes Obes Metab 2014;16:833–840
    1. Del Prato S, Camisasca R, Wilson C, Fleck P. Durability of the efficacy and safety of alogliptin compared with glipizide in type 2 diabetes mellitus: a 2-year study. Diabetes Obes Metab 2014;16:1239–1246
    1. Mishriky BM, Cummings DM, Tanenberg RJ. The efficacy and safety of DPP4 inhibitors compared to sulfonylureas as add-on therapy to metformin in patients with type 2 diabetes: a systematic review and meta-analysis. Diabetes Res Clin Pract 2015;109:378–388
    1. Khunti K, Chatterjee S, Gerstein HC, et al. Do sulphonylureas still have a place in clinical practice? Lancet Diabetes Endocrinol 2018;Feb 28:pii:S2213-8587(18)30025-1.
    1. Gangji AS, Cukierman T, Gerstein HC, Goldsmith CH, Clase CM. A systematic review and meta-analysis of hypoglycemia and cardiovascular events: a comparison of glyburide with other secretagogues and with insulin. Diabetes Care 2007;30:389–394
    1. Chan SP, Colagiuri S. Systematic review and meta-analysis of the efficacy and hypoglycemic safety of gliclazide versus other insulinotropic agents. Diabetes Res Clin Pract 2015;110:75–81
    1. Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 2008;359:1577–1589
    1. Erpeldinger S, Rehman MB, Berkhout C, et al. . Efficacy and safety of insulin in type 2 diabetes: meta-analysis of randomised controlled trials. BMC Endocr Disord 2016;16:39.
    1. Owens DR, Traylor L, Mullins P, Landgraf W. Patient-level meta-analysis of efficacy and hypoglycaemia in people with type 2 diabetes initiating insulin glargine 100U/mL or neutral protamine Hagedorn insulin analysed according to concomitant oral antidiabetes therapy. Diabetes Res Clin Pract 2017;124:57–65
    1. Goldman J, Kapitza C, Pettus J, Heise T. Understanding how pharmacokinetic and pharmacodynamic differences of basal analog insulins influence clinical practice. Curr Med Res Opin 2017;33:1821–1831
    1. Freemantle N, Chou E, Frois C, et al. . Safety and efficacy of insulin glargine 300 u/mL compared with other basal insulin therapies in patients with type 2 diabetes mellitus: a network meta-analysis. BMJ Open 2016;6:e009421
    1. Russell-Jones D, Gall M-A, Niemeyer M, Diamant M, Del Prato S. Insulin degludec results in lower rates of nocturnal hypoglycaemia and fasting plasma glucose vs. insulin glargine: a meta-analysis of seven clinical trials. Nutr Metab Cardiovasc Dis 2015;25:898–905
    1. Lipska KJ, Parker MM, Moffet HH, Huang ES, Karter AJ. Association of initiation of basal insulin analogs vs neutral protamine hagedorn insulin with hypoglycemia-related emergency department visits or hospital admissions and with glycemic control in patients with type 2 diabetes. JAMA 2018;320:53–62
    1. Marso SP, McGuire DK, Zinman B, et al. .; DEVOTE Study Group . Efficacy and safety of degludec versus glargine in type 2 diabetes. N Engl J Med 2017;377:723–732
    1. Rosenstock J, Hollander P, Bhargava A, et al. . Similar efficacy and safety of LY2963016 insulin glargine and insulin glargine (Lantus®) in patients with type 2 diabetes who were insulin-naïve or previously treated with insulin glargine: a randomized, double-blind controlled trial (the ELEMENT 2 study). Diabetes Obes Metab 2015;17:734–741
    1. Gerstein HC, Bosch J, Dagenais GR, et al. .; ORIGIN Trial Investigators . Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med 2012;367:319–328
    1. Riddle MC, Yki-Järvinen H, Bolli GB, et al. . One-year sustained glycaemic control and less hypoglycaemia with new insulin glargine 300 U/ml compared with 100 U/ml in people with type 2 diabetes using basal plus meal-time insulin: the EDITION 1 12-month randomized trial, including 6-month extension. Diabetes Obes Metab 2015;17:835–842
    1. Yki-Järvinen H, Bergenstal R, Ziemen M, et al. .; EDITION 2 Study Investigators . New insulin glargine 300 units/mL versus glargine 100 units/mL in people with type 2 diabetes using oral agents and basal insulin: glucose control and hypoglycemia in a 6-month randomized controlled trial (EDITION 2). Diabetes Care 2014;37:3235–3243
    1. Riddle MC, Bolli GB, Ziemen M, Muehlen-Bartmer I, Bizet F, Home PD; EDITION 1 Study Investigators . New insulin glargine 300 units/mL versus glargine 100 units/mL in people with type 2 diabetes using basal and mealtime insulin: glucose control and hypoglycemia in a 6-month randomized controlled trial (EDITION 1). Diabetes Care 2014;37:2755–2762
    1. Khunti K, Damci T, Husemoen LL, Babu V, Liebl A. Exploring the characteristics of suboptimally controlled patients after 24 weeks of basal insulin treatment: an individualized approach to intensification. Diabetes Res Clin Pract 2017;123:209–217
    1. Jensen MD, Ryan DH, Apovian CM, et al. .; American College of Cardiology/American Heart Association Task Force on Practice Guidelines; Obesity Society . 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. J Am Coll Cardiol 2014;63(25 Pt B):2985–3023
    1. Garvey WT, Mechanick JI, Brett EM, et al. .; Reviewers of the AACE/ACE Obesity Clinical Practice Guidelines . American Association of Clinical Endocrinologists and American College of Endocrinology Comprehensive Clinical Practice Guidelines for Medical Care of Patients with Obesity. Endocr Pract 2016;22(Suppl. 3):1–203
    1. Apovian CM, Aronne LJ, Bessesen DH, et al. .; Endocrine Society . Pharmacological management of obesity: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2015;100:342–362
    1. Moyer VA; U.S. Preventive Services Task Force . Screening for and management of obesity in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2012;157:373–378
    1. Van Gaal L, Dirinck E. Pharmacological approaches in the treatment and maintenance of weight loss. Diabetes Care 2016;39(Suppl. 2):S260–S267
    1. Khera R, Pandey A, Chandar AK, et al. . Effects of weight-loss medications on cardiometabolic risk profiles: a systematic review and network meta-analysis. Gastroenterology 2018;154:1309–1319.e7
    1. Davies MJ, Bergenstal R, Bode B, et al. .; NN8022-1922 Study Group . Efficacy of liraglutide for weight loss among patients with type 2 diabetes: the SCALE diabetes randomized clinical trial. JAMA 2015;314:687–699
    1. Schauer PR, Bhatt DL, Kirwan JP, et al. .; STAMPEDE Investigators . Bariatric surgery versus intensive medical therapy for diabetes—3-year outcomes. N Engl J Med 2014;370:2002–2013
    1. Schauer PR, Bhatt DL, Kirwan JP, et al. .; STAMPEDE Investigators . Bariatric surgery versus intensive medical therapy for diabetes—5-year outcomes. N Engl J Med 2017;376:641–651
    1. Ikramuddin S, Korner J, Lee W-J, et al. . Lifestyle intervention and medical management with vs without Roux-en-Y gastric bypass and control of hemoglobin A1c, LDL cholesterol, and systolic blood pressure at 5 years in the diabetes surgery study. JAMA 2018;319:266–278
    1. Dixon JB, O’Brien PE, Playfair J, et al. . Adjustable gastric banding and conventional therapy for type 2 diabetes: a randomized controlled trial. JAMA 2008;299:316–323
    1. Mingrone G, Panunzi S, De Gaetano A, et al. . Bariatric surgery versus conventional medical therapy for type 2 diabetes. N Engl J Med 2012;366:1577–1585
    1. Sjöström L, Peltonen M, Jacobson P, et al. . Association of bariatric surgery with long-term remission of type 2 diabetes and with microvascular and macrovascular complications. JAMA 2014;311:2297–2304
    1. Mingrone G, Panunzi S, De Gaetano A, 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;386:964–973
    1. Rubino F, Nathan DM, Eckel RH, et al. .; Delegates of the 2nd Diabetes Surgery Summit . Metabolic surgery in the treatment algorithm for type 2 diabetes: a joint statement by international diabetes organizations. Diabetes Care 2016;39:861–877
    1. Maggard-Gibbons M, Maglione M, Livhits M, et al. . Bariatric surgery for weight loss and glycemic control in nonmorbidly obese adults with diabetes: a systematic review. JAMA 2013;309:2250–2261
    1. Mingrone G, Bornstein S, Le Roux CW. Optimisation of follow-up after metabolic surgery. Lancet Diabetes Endocrinol 2018;6:487–499
    1. Conason A, Teixeira J, Hsu C-H, Puma L, Knafo D, Geliebter A. Substance use following bariatric weight loss surgery. JAMA Surg 2013;148:145–150
    1. Dawes AJ, Maggard-Gibbons M, Maher AR, et al. . Mental health conditions among patients seeking and undergoing bariatric surgery: a meta-analysis. JAMA 2016;315:150–163
    1. Mechanick JI, Kushner RF, Sugerman HJ, et al. (2009) American Association of Clinical Endocrinologists, The Obesity Society, and American Society for Metabolic & Bariatric Surgery medical guidelines for clinical practice for the perioperative nutritional, metabolic, and nonsurgical support of the bariatric surgery patient. Obesity (Silver Spring) 2009;17(Suppl. 1):S1–S70, v
    1. Mechanick JI, Youdim A, Jones DB, et al. (2013) Clinical practice guidelines for the perioperative nutritional, metabolic, and nonsurgical support of the bariatric surgery patient–2013 update: cosponsored by American Association of Clinical Endocrinologists, The Obesity Society, and American Society for Metabolic & Bariatric Surgery. Obesity (Silver Spring) 2013;21(Suppl. 1):S1–S27
    1. 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;16:410–417
    1. Abdul-Ghani MA, Puckett C, Triplitt C, et al. . Initial combination therapy with metformin, pioglitazone and exenatide is more effective than sequential add-on therapy in subjects with new-onset diabetes. Results from the Efficacy and Durability of Initial Combination Therapy for Type 2 Diabetes (EDICT): a randomized trial. Diabetes Obes Metab 2015;17:268–275
    1. Vijayakumar TM, Jayram J, Meghana Cheekireddy V, Himaja D, Dharma Teja Y, Narayanasamy D. Safety, efficacy, and bioavailability of fixed-dose combinations in type 2 diabetes mellitus: a systematic updated review. Curr Ther Res Clin Exp 2017;84:4–9
    1. Mearns ES, Saulsberry WJ, White CM, et al. . Efficacy and safety of antihyperglycaemic drug regimens added to metformin and sulphonylurea therapy in type 2 diabetes: a network meta-analysis. Diabet Med 2015;32:1530–1540
    1. Henry RR, Murray AV, Marmolejo MH, Hennicken D, Ptaszynska A, List JF. Dapagliflozin, metformin XR, or both: initial pharmacotherapy for type 2 diabetes, a randomised controlled trial. Int J Clin Pract 2012;66:446–456
    1. Buse JB, Peters A, Russell-Jones D, et al. . Is insulin the most effective injectable antihyperglycaemic therapy? Diabetes Obes Metab 2015;17:145–151
    1. Vaccaro O, Masulli M, Nicolucci A, et al. .; Thiazolidinediones Or Sulfonylureas Cardiovascular Accidents Intervention Trial () study group; Italian Diabetes Society . Effects on the incidence of cardiovascular events of the addition of pioglitazone versus sulfonylureas in patients with type 2 diabetes inadequately controlled with metformin (): a randomised, multicentre trial. Lancet Diabetes Endocrinol 2017;5:887–897
    1. Wang Z, Sun J, Han R, et al. . Efficacy and safety of sodium-glucose cotransporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors as monotherapy or add-on to metformin in patients with type 2 diabetes mellitus: a systematic review and meta-analysis. Diabetes Obes Metab 2018;20:113–120
    1. 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;30:269–283
    1. Leiter LA, Yoon K-H, Arias P, et al. . Canagliflozin provides durable glycemic improvements and body weight reduction over 104 weeks versus glimepiride in patients with type 2 diabetes on metformin: a randomized, double-blind, phase 3 study. Diabetes Care 2015;38:355–364
    1. Del Prato S, Nauck M, Durán-Garcia S, et al. . Long-term glycaemic response and tolerability of dapagliflozin versus a sulphonylurea as add-on therapy to metformin in patients with type 2 diabetes: 4-year data. Diabetes Obes Metab 2015;17:581–590
    1. Ridderstråle M, Andersen KR, Zeller C, Kim G, Woerle HJ, Broedl UC; EMPA-REG H2H-SU trial investigators . Comparison of empagliflozin and glimepiride as add-on to metformin in patients with type 2 diabetes: a 104-week andomized, active-controlled, double-blind, phase 3 trial. Lancet Diabetes Endocrinol 2014;2:691–700
    1. Zhang Y, Hong J, Chi J, Gu W, Ning G, Wang W. Head-to-head comparison of dipeptidyl peptidase-IV inhibitors and sulfonylureas – a meta-analysis from randomized clinical trials. Diabetes Metab Res Rev 2014;30:241–256
    1. Foroutan N, Muratov S, Levine M. Safety and efficacy of dipeptidyl peptidase-4 inhibitors vs sulfonylurea in metformin-based combination therapy for type 2 diabetes mellitus: systematic review and meta-analysis. Clin Invest Med 2016;39:E48–E62
    1. Chen K, Kang D, Yu M, et al. . Direct head-to-head comparison of glycaemic durability of dipeptidyl peptidase-4 inhibitors and sulphonylureas in patients with type 2 diabetes mellitus: a meta-analysis of long-term randomized controlled trials. Diabetes Obes Metab 2018;20:1029–1033
    1. Zaccardi F, Dhalwani NN, Dales J, et al. . Comparison of glucose-lowering agents after dual therapy failure in type 2 diabetes: a systematic review and network meta-analysis of randomized controlled trials. Diabetes Obes Metab 2018;20:985–997
    1. Downes MJ, Bettington EK, Gunton JE, Turkstra E. Triple therapy in type 2 diabetes; a systematic review and network meta-analysis. PeerJ 2015;3:e1461.
    1. Lee CMY, Woodward M, Colagiuri S. Triple therapy combinations for the treatment of type 2 diabetes – a network meta-analysis. Diabetes Res Clin Pract 2016;116:149–158
    1. Lukashevich V, Del Prato S, Araga M, Kothny W. Efficacy and safety of vildagliptin in patients with type 2 diabetes mellitus inadequately controlled with dual combination of metformin and sulphonylurea. Diabetes Obes Metab 2014;16:403–409
    1. Hong AR, Lee J, Ku EJ, et al. . Comparison of vildagliptin as an add-on therapy and sulfonylurea dose-increasing therapy in patients with inadequately controlled type 2 diabetes using metformin and sulfonylurea (VISUAL study): a randomized trial. Diabetes Res Clin Pract 2015;109:141–148
    1. Moses RG, Kalra S, Brook D, et al. . A randomized controlled trial of the efficacy and safety of saxagliptin as add-on therapy in patients with type 2 diabetes and inadequate glycaemic control on metformin plus a sulphonylurea. Diabetes Obes Metab 2014;16:443–450
    1. Moses RG, Round E, Shentu Y, et al. . A randomized clinical trial evaluating the safety and efficacy of sitagliptin added to the combination of sulfonylurea and metformin in patients with type 2 diabetes mellitus and inadequate glycemic control. J Diabetes 2016;8:701–711
    1. Singh S, Wright EE Jr, Kwan AYM, et al. . Glucagon-like peptide-1 receptor agonists compared with basal insulins for the treatment of type 2 diabetes mellitus: a systematic review and meta-analysis. Diabetes Obes Metab 2017;19:228–238
    1. Levin PA, Nguyen H, Wittbrodt ET, Kim SC. Glucagon-like peptide-1 receptor agonists: a systematic review of comparative effectiveness research. Diabetes Metab Syndr Obes 2017;10:123–139
    1. Abd El Aziz MS, Kahle M, Meier JJ, Nauck MA. A meta-analysis comparing clinical effects of short- or long-acting GLP-1 receptor agonists versus insulin treatment from head-to-head studies in type 2 diabetic patients. Diabetes Obes Metab 2017;19:216–227
    1. Eng C, Kramer CK, Zinman B, Retnakaran R. Glucagon-like peptide-1 receptor agonist and basal insulin combination treatment for the management of type 2 diabetes: a systematic review and meta-analysis. Lancet 2014;384:2228–2234
    1. Aroda VR, Bailey TS, Cariou B, et al. . Effect of adding insulin degludec to treatment in patients with type 2 diabetes inadequately controlled with metformin and liraglutide: a double-blind randomized controlled trial (BEGIN: ADD TO GLP-1 Study). Diabetes Obes Metab 2016;18:663–670
    1. Aschner P, Sethi B, Gomez-Peralta F, et al. . Insulin glargine compared with premixed insulin for management of insulin-naïve type 2 diabetes patients uncontrolled on oral antidiabetic drugs: the open-label, randomized GALAPAGOS study. J Diabetes Complications 2015;29:838–845
    1. Rosenstock J, Fonseca V, Schinzel S, Dain MP, Mullins P, Riddle M. Reduced risk of hypoglycemia with once-daily glargine versus twice-daily NPH and number needed to harm with NPH to demonstrate the risk of one additional hypoglycemic event in type 2 diabetes: evidence from a long-term controlled trial. J Diabetes Complications 2014;28:742–749
    1. Tang H, Cui W, Li D, et al. . Sodium-glucose co-transporter 2 inhibitors in addition to insulin therapy for management of type 2 diabetes mellitus: a meta-analysis of randomized controlled trials. Diabetes Obes Metab 2017;19:142–147
    1. Rosenstock J, Jelaska A, Zeller C, Kim G, Broedl UC, Woerle HJ; EMPA-REG BASALTM trial investigators . Impact of empagliflozin added on to basal insulin in type 2 diabetes inadequately controlled on basal insulin: a 78-week randomized, double-blind, placebo-controlled trial. Diabetes Obes Metab 2015;17:936–948
    1. Rosenstock J, Jelaska A, Frappin G, et al. .; EMPA-REG MDI Trial Investigators . Improved glucose control with weight loss, lower insulin doses, and no increased hypoglycemia with empagliflozin added to titrated multiple daily injections of insulin in obese inadequately controlled type 2 diabetes. Diabetes Care 2014;37:1815–1823
    1. Yang W, Cai X, Gao X, Chen Y, Chen L, Ji L. Addition of dipeptidyl peptidase-4 inhibitors to insulin treatment in type 2 diabetes patients: a meta-analysis. J Diabetes Investig 2018;9:813–821
    1. Min SH, Yoon J-H, Hahn S, Cho YM. Comparison between SGLT2 inhibitors and DPP4 inhibitors added to insulin therapy in type 2 diabetes: a systematic review with indirect comparison meta-analysis: SGLT2 or DPP4 inhibitor with insulin. Diabetes Metab Res Rev 2017;33:e2818
    1. Wysham CH, Lin J, Kuritzky L. Safety and efficacy of a glucagon-like peptide-1 receptor agonist added to basal insulin therapy versus basal insulin with or without a rapid-acting insulin in patients with type 2 diabetes: results of a meta-analysis. Postgrad Med 2017;129:436–445
    1. Maiorino MI, Chiodini P, Bellastella G, Capuano A, Esposito K, Giugliano D. Insulin and glucagon-like peptide 1 receptor agonist combination therapy in type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials. Diabetes Care 2017;40:614–624
    1. Gough SCL, Bode BW, Woo VC, et al. . One-year efficacy and safety of a fixed combination of insulin degludec and liraglutide in patients with type 2 diabetes: results of a 26-week extension to a 26-week main trial. Diabetes Obes Metab 2015;17:965–973
    1. Rosenstock J, Aronson R, Grunberger G, et al. .; LixiLan-O Trial Investigators . Benefits of LixiLan, a titratable fixed-ratio combination of insulin glargine plus lixisenatide, versus insulin glargine and lixisenatide monocomponents in type 2 diabetes inadequately controlled on oral agents: the LixiLan-O randomized trial. Diabetes Care 2016;39:2026–2035
    1. Aroda VR, Rosenstock J, Wysham C, et al. .; LixiLan-L Trial Investigators . Efficacy and safety of LixiLan, a titratable fixed-ratio combination of insulin glargine plus lixisenatide in type 2 diabetes inadequately controlled on basal insulin and metformin: the LixiLan-L randomized trial. Diabetes Care 2016;39:1972–1980
    1. Garber AJ, Wahlen J, Wahl T, et al. . Attainment of glycaemic goals in type 2 diabetes with once-, twice-, or thrice-daily dosing with biphasic insulin aspart 70/30 (the 1-2-3 study). Diabetes Obes Metab 2006;8:58–66
    1. Linjawi S, Lee B-W, Tabak Ö, Lövdahl S, Werther S, Abusnana S. A 32-week randomized comparison of stepwise insulin intensification of biphasic insulin aspart (BIAsp 30) versus basal-bolus therapy in insulin-naïve patients with type 2 diabetes. Diabetes Ther 2018;9:1–11
    1. Raccah D, Huet D, Dib A, et al. . Review of basal-plus insulin regimen options for simpler insulin intensification in people with type 2 diabetes mellitus. Diabet Med 2017;34:1193–1204
    1. Rodbard HW, Visco VE, Andersen H, Hiort LC, Shu DH. Treatment intensification with stepwise addition of prandial insulin aspart boluses compared with full basal-bolus therapy (FullSTEP Study): a randomised, treat-to-target clinical trial. Lancet Diabetes Endocrinol 2014;2:30–37
    1. Giugliano D, Chiodini P, Maiorino MI, Bellastella G, Esposito K. Intensification of insulin therapy with basal-bolus or premixed insulin regimens in type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials. Endocrine 2016;51:417–428
    1. 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;32:585–594
    1. Anyanwagu U, Mamza J, Gordon J, Donnelly R, Idris I. Premixed vs basal-bolus insulin regimen in type 2 diabetes: comparison of clinical outcomes from randomized controlled trials and real-world data. Diabet Med 2017;34:1728–1736
    1. Aronson R, Reznik Y, Conget I, et al. .; OpT2mise Study Group . Sustained efficacy of insulin pump therapy compared with multiple daily injections in type 2 diabetes: 12-month data from the OpT2mise randomized trial. Diabetes Obes Metab 2016;18:500–507
    1. Kelly S, Martin S, Kuhn I, Cowan A, Brayne C, Lafortune L. Barriers and facilitators to the uptake and maintenance of healthy behaviours by people at mid-life: a rapid systematic review. PLoS One 2016;11:e0145074.
    1. Gee PM, Greenwood DA, Paterniti DA, Ward D, Miller LM. The eHealth Enhanced Chronic Care Model: a theory derivation approach. J Med Internet Res 2015;17:e86.
    1. Faruque LI, Wiebe N, Ehteshami-Afshar A, et al. .; Alberta Kidney Disease Network . Effect of telemedicine on glycated hemoglobin in diabetes: a systematic review and meta-analysis of randomized trials. CMAJ 2017;189:E341–E364
    1. Lee SWH, Chan CKY, Chua SS, Chaiyakunapruk N. Comparative effectiveness of telemedicine strategies on type 2 diabetes management: a systematic review and network meta-analysis. Sci Rep 2017;7:12680.

Source: PubMed

3
Abonnieren