diaendoСахарный диабетDiabetes mellitus2072-03512072-0378Endocrinology research centre10.14341/DM8793diaendo-8793Research ArticleДиагностика, контроль, лечениеDiagnosis, control, treatmentВыбор второй линии терапии у пациентов с сахарным диабетом 2 типа: активация метаболической памятиSecond line therapy in type 2 diabetes: legacy effect activationhttps://orcid.org/0000-0001-6612-6851ШестаковаЕкатерина АлексеевнаShestakovaEkaterina A.

кандидат медицинских наук, ведущий научный сотрудник консультативно-диагностического отделения

MD, PhD

katiashestakova@mail.ru<p>ФГБУ Национальный медицинский исследовательский центр эндокринологии Минздрава России</p>Россия<p>Endocrinology Research Centre</p>Russian Federation201713122017205356362Copyright &#x00A9; Шестакова Е.А., 20172017Шестакова Е.А.Shestakova E.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.dia-endojournals.ru/jour/article/view/8793

Сахарный диабет 2 типа (СД2) – заболевание, от осложнений которого во всем мире погибают сотни тысяч человек в год. С каждым годом появляются новые препараты, а почти каждое десятилетие – классы препаратов, направленные на снижение гликемии. К сожалению, несмотря на это, многие пациенты с СД2 не достигают компенсации углеводного обмена. Согласно большинству рекомендаций по лечению СД2, первой линией терапии остается метформин. Выбор того или иного препарата для формирования комбинации с метформином осуществляется в соответствии с международными и локальными руководствами, часто оставляющими выбор второй линии терапии за врачом. Поэтому актуальным остается вопрос определения целевых групп пациентов сахароснижающего препарата второй линии. В данном обзоре представлены данные о влиянии различных групп сахароснижающих препаратов на прогрессирование микро- и макрососудистых осложнений СД. Рассматривается целесообразность ранней интенсификации сахароснижающей терапии с целью активации «метаболической памяти» – механизма замедления прогрессирования осложнений СД. Длительное поддержание компенсации углеводного обмена в дебюте заболевания с помощью комбинации сахароснижающих препаратов может служить основой первичной профилактики сердечно-сосудистых исходов у пациентов с СД.

Type 2 diabetes causes hundred thousand deaths worldwide every year. Though new antidiabetic drugs appear annually and new classes of drugs are invented approximately every ten years still a lot of type 2 diabetic patients remain to be out of the target glycemic levels.

According to most of the guidelines for type 2 diabetes,treatment metformin is the first line therapy for this disease. The choice of second-line antidiabetic drug usually depends on doctors’ preference. That is why defining the correct drug for exact patient is still an urgent question. This review provides data on antidiabetic drugspotential for preventing the progression of micro- and macrovascular complications.The question of the potential of early antidiabetic therapy intensification to activate legacy effect is debated. Early and lasting compensation of diabetes with the use of multiple drugs can become a basis for primary prevention of cardiovascular disease in such patients.

сахарный диабет 2 типасахароснижающая терапияиДПП-4иНГЛТ-2микрососудистые осложнениямакрососудистые осложненияметаболическая памятьtype 2 diabeteshypoglycemic drugsDPP-4 inhibitorsSGLT-2 inhibitorsmicrovascular complicationsmacrovascular complicationslegacy effectПоисково-аналитическая работа проведена в рамках выполнения государственного задания «Взаимодействие генетических, метаболических и воспалительных факторов развития и прогрессирования сосудистых осложнений сахарного диабета, в том числе после хирургически индуцированной ремиссии диабета» (НИОКТР АААА-А17-117012610110-9).ReferencesAmerican Diabetes Association. Pharmacologic Approaches to Glycemic Treatment. Diabetes Care. 2017;40(Suppl 1):64-74. doi: 10.2337/dc17-S011American Diabetes Association. Pharmacologic Approaches to Glycemic Treatment. Diabetes Care. 2017;40(Suppl 1):64-74. doi: 10.2337/dc17-S011American Diabetes Association. Standards of medical care in diabetes-2016: summary of revisions. Diabetes Care. 2016;39(Suppl 1):4–5. doi: 10.2337/dc16-S003American Diabetes Association. Standards of medical care in diabetes-2016: summary of revisions. Diabetes Care. 2016;39(Suppl 1):4–5. doi: 10.2337/dc16-S003Nathan DM, Buse JB, Kahn SE, et al. Rationale and design of the glycemia reduction approaches in diabetes: a comparative effectiveness study (GRADE). Diabetes Care. 2013;36(8):2254-2261. doi:10.2337/dc13-0356Nathan DM, Buse JB, Kahn SE, et al. Rationale and design of the glycemia reduction approaches in diabetes: a comparative effectiveness study (GRADE). Diabetes Care. 2013;36(8):2254-2261. doi:10.2337/dc13-0356Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2015;38(1):140-149. doi: 10.2337/dc14-2441Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2015;38(1):140-149. doi: 10.2337/dc14-2441Schernthaner G, Mogensen CE, Schernthaner GH. The effects of GLP-1 analogues, DPP-4 inhibitors and SGLT2 inhibitors on the renal system. Diab Vasc Dis Res. 2014;11(5):306-323. doi: 10.1177/1479164114542802Schernthaner G, Mogensen CE, Schernthaner GH. The effects of GLP-1 analogues, DPP-4 inhibitors and SGLT2 inhibitors on the renal system. Diab Vasc Dis Res. 2014;11(5):306-323. doi: 10.1177/1479164114542802U.S. Renal Data System. USRDS 2012 annual data report: atlas of chronic kidney disease and end-stage renal disease in the United States. Bethesda: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; 2012. Available from: https://www.usrds.org/atlas12.aspx.U.S. Renal Data System. USRDS 2012 annual data report: atlas of chronic kidney disease and end-stage renal disease in the United States. Bethesda: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; 2012. Available from: https://www.usrds.org/atlas12.aspx.Дедов И.И., Шестакова М.В., Майоров А.Ю., и др. Алгоритмы специализированной медицинской помощи больным сахарным диабетом / Под редакцией И.И. Дедова, М.В. Шестаковой, А.Ю. Майорова. – 8-й выпуск // Сахарный диабет. – 2017. – Т. 20. – №1S. – C. 1-121. [Dedov II, Shestakova MV, Mayorov AY, et al. Standards of specialized diabetes care. Edited by Dedov II, Shestakova MV, Mayorov AY. 8th edition. Diabetes mellitus. 2017;20(1S):1-121. (In Russ.)] doi: 10.14341/DM8146Дедов И.И., Шестакова М.В., Майоров А.Ю., и др. Алгоритмы специализированной медицинской помощи больным сахарным диабетом / Под редакцией И.И. Дедова, М.В. Шестаковой, А.Ю. Майорова. – 8-й выпуск // Сахарный диабет. – 2017. – Т. 20. – №1S. – C. 1-121. [Dedov II, Shestakova MV, Mayorov AY, et al. Standards of specialized diabetes care. Edited by Dedov II, Shestakova MV, Mayorov AY. 8th edition. Diabetes mellitus. 2017;20(1S):1-121. (In Russ.)] doi: 10.14341/DM8146Athyros VG, Mitsiou EK, Tziomalos K, et al. Impact of managing atherogenic dyslipidemia on cardiovascular outcome across different stages of diabetic nephropathy. Expert Opin Pharmacother. 2010;11(5): 723–730. doi: 10.1517/14656560903575654Athyros VG, Mitsiou EK, Tziomalos K, et al. Impact of managing atherogenic dyslipidemia on cardiovascular outcome across different stages of diabetic nephropathy. Expert Opin Pharmacother. 2010;11(5): 723–730. doi: 10.1517/14656560903575654Alter ML, Ott IM, von Websky K, et al. DPP-4 inhibition on top of angiotensin receptor blockade offers a new therapeutic approach for diabetic nephropathy. Kidney Blood Press Res. 2012;36(1):119-130. doi: 10.1159/000341487Alter ML, Ott IM, von Websky K, et al. DPP-4 inhibition on top of angiotensin receptor blockade offers a new therapeutic approach for diabetic nephropathy. Kidney Blood Press Res. 2012;36(1):119-130. doi: 10.1159/000341487Fujita H, Tania H, Murayama H et al. DPP-4 inhibition with alogliptin on top of angiotensin II type 1 receptor blockade ameliorates albuminuria via up-regulation of SDF-1α in type 2 diabetic patients with incipient nephropathy. Endocrine Journal. 2014;61(2):159-166. doi: 10.1507/endocrj.EJ13-0305Fujita H, Tania H, Murayama H et al. DPP-4 inhibition with alogliptin on top of angiotensin II type 1 receptor blockade ameliorates albuminuria via up-regulation of SDF-1α in type 2 diabetic patients with incipient nephropathy. Endocrine Journal. 2014;61(2):159-166. doi: 10.1507/endocrj.EJ13-0305Корбут А.И., Климонтов В.В. Терапия, основанная на инкретинах: почечные эффекты // Сахарный диабет. – 2016. – Т. 19. – №1. – C. 53-63. [Korbut AI, Klimontov VV. Incretin-based therapy: renal effects. Diabetes mellitus. 2016;19(1):53-63. (In Russ.)] doi: 10.14341/DM7727Корбут А.И., Климонтов В.В. Терапия, основанная на инкретинах: почечные эффекты // Сахарный диабет. – 2016. – Т. 19. – №1. – C. 53-63. [Korbut AI, Klimontov VV. Incretin-based therapy: renal effects. Diabetes mellitus. 2016;19(1):53-63. (In Russ.)] doi: 10.14341/DM7727Groop PH, Cooper ME, Perkovic V, et al. Dipeptidyl peptidase-4 inhibition with linagliptin and effects on hyperglycaemia and albuminuria in patients with type 2 diabetes and renal dysfunction: Rationale and design of the MARLINA-T2DTM trial. Diab Vasc Dis Res. 2015;12(6):455-462. doi: 10.1177/1479164115579002Groop PH, Cooper ME, Perkovic V, et al. Dipeptidyl peptidase-4 inhibition with linagliptin and effects on hyperglycaemia and albuminuria in patients with type 2 diabetes and renal dysfunction: Rationale and design of the MARLINA-T2DTM trial. Diab Vasc Dis Res. 2015;12(6):455-462. doi: 10.1177/1479164115579002Wanner C, Inzucchi SE, Lachin JM, et al. Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes. N Engl J Med. 2016;375(4):323-334. doi: 10.1056/NEJMoa1515920Wanner C, Inzucchi SE, Lachin JM, et al. Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes. N Engl J Med. 2016;375(4):323-334. doi: 10.1056/NEJMoa1515920Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med. 2017;377:644-657. doi: 10.1056/NEJMoa1611925Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med. 2017;377:644-657. doi: 10.1056/NEJMoa1611925Дедов И.И., Шестакова М.В., Викулова О.К. Эпидемиология сахарного диабета в Российской Федерации: клинико-статистический анализ по данным Федерального регистра сахарного диабета // Сахарный диабет. – 2017. – Т. 20. – №1. – C. 13-41 [Dedov II, Shestakova MV, Vikulova OK. Epidemiology of diabetes mellitus in Russian Federation: clinical and statistical report according to the federal diabetes registry. Diabetes mellitus. 2017;20(1):13-41. (In Russ.)] doi: 10.14341/DM8664Дедов И.И., Шестакова М.В., Викулова О.К. Эпидемиология сахарного диабета в Российской Федерации: клинико-статистический анализ по данным Федерального регистра сахарного диабета // Сахарный диабет. – 2017. – Т. 20. – №1. – C. 13-41 [Dedov II, Shestakova MV, Vikulova OK. Epidemiology of diabetes mellitus in Russian Federation: clinical and statistical report according to the federal diabetes registry. Diabetes mellitus. 2017;20(1):13-41. (In Russ.)] doi: 10.14341/DM8664Butler JM, Guthrie SM, Koc M, et al. SDF-1 is both necessary and sufficient to promote proliferative retinopathy. J Clin Invest. 2005;115(1):86–93. doi: 10.1172/JCI22869Butler JM, Guthrie SM, Koc M, et al. SDF-1 is both necessary and sufficient to promote proliferative retinopathy. J Clin Invest. 2005;115(1):86–93. doi: 10.1172/JCI22869Dietrich N, Kolibabka M, Busch S, et al. The DPP4 Inhibitor Linagliptin Protects from Experimental Diabetic Retinopathy. PLoS One. 2016;11(12):e0167853. doi: 10.1371/journal.pone.0167853Dietrich N, Kolibabka M, Busch S, et al. The DPP4 Inhibitor Linagliptin Protects from Experimental Diabetic Retinopathy. PLoS One. 2016;11(12):e0167853. doi: 10.1371/journal.pone.0167853Kolaczynski WM, Hankins M, Ong SH, et al. Microvascular Outcomes in Patients with Type 2 Diabetes Treated with Vildagliptin vs. Sulfonylurea: A Retrospective Study Using German Electronic Medical Records. Diabetes Ther. 2016;7(3):483-496. doi: 10.1007/s13300-016-0177-8Kolaczynski WM, Hankins M, Ong SH, et al. Microvascular Outcomes in Patients with Type 2 Diabetes Treated with Vildagliptin vs. Sulfonylurea: A Retrospective Study Using German Electronic Medical Records. Diabetes Ther. 2016;7(3):483-496. doi: 10.1007/s13300-016-0177-8Wanner C, Lee C, Woerle HJ, et al. Empagliflozin and microvascular outcomes in EMPA-REG OUTCOME. Diabetologia. 2016;59(Suppl 1):483-484. doi: 10.1007/s00125-016-4046-9Wanner C, Lee C, Woerle HJ, et al. Empagliflozin and microvascular outcomes in EMPA-REG OUTCOME. Diabetologia. 2016;59(Suppl 1):483-484. doi: 10.1007/s00125-016-4046-9Stratton IM, Adler AI, Neil HA, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000;321(7258):405-412. doi: 10.1136/bmj.321.7258.405Stratton IM, Adler AI, Neil HA, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000;321(7258):405-412. doi: 10.1136/bmj.321.7258.405Juutilainen A, Lehto S, Ronnemaa T, et al. Retinopathy predicts cardiovascular mortality in type 2 diabetic men and women. Diabetes Care. 2007;30(2):292–299. doi: 10.2337/dc06-1747Juutilainen A, Lehto S, Ronnemaa T, et al. Retinopathy predicts cardiovascular mortality in type 2 diabetic men and women. Diabetes Care. 2007;30(2):292–299. doi: 10.2337/dc06-1747Emerging Risk Factors Collaboration; Di Angelantonio E, Gao P, et al. Glycated hemoglobin measurement and prediction of cardiovascular disease. JAMA. 2014;311(12):1225–33. doi: 10.1001/jama.2014.1873Emerging Risk Factors Collaboration; Di Angelantonio E, Gao P, et al. Glycated hemoglobin measurement and prediction of cardiovascular disease. JAMA. 2014;311(12):1225–33. doi: 10.1001/jama.2014.1873Boussageon R, Bejan-Angoulvant T, Saadatian-Elahi M, et al. Effect of intensive glucose lowering treatment on all cause mortality, cardiovascular death, and microvascular events in type 2 diabetes: meta-analysis of randomised controlled trials. BMJ. 2011;343:d4169. doi: 10.1136/bmj.d4169Boussageon R, Bejan-Angoulvant T, Saadatian-Elahi M, et al. Effect of intensive glucose lowering treatment on all cause mortality, cardiovascular death, and microvascular events in type 2 diabetes: meta-analysis of randomised controlled trials. BMJ. 2011;343:d4169. doi: 10.1136/bmj.d4169Gaede P, Vedel P, Larsen N, et al. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Eng J Med. 2003;348(5):383–393. doi: 10.1056/NEJMoa021778Gaede P, Vedel P, Larsen N, et al. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Eng J Med. 2003;348(5):383–393. doi: 10.1056/NEJMoa021778Guidance for Industry. Diabetes mellitus—evaluating cardiovascular risk in new antidiabetic therapies to treat type 2 diabetes. 2008. Silver Spring: U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER); 2008. Available from: https://www.fda.gov/downloads/Drugs/.../Guidances/ucm071627.pdf.Guidance for Industry. Diabetes mellitus—evaluating cardiovascular risk in new antidiabetic therapies to treat type 2 diabetes. 2008. Silver Spring: U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER); 2008. Available from: https://www.fda.gov/downloads/Drugs/.../Guidances/ucm071627.pdf.Scirica BM, Bhatt DL, Braunwald E, et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Eng J Med. 2013;369(14):1317–1326. doi: 10.1056/NEJMoa1307684Scirica BM, Bhatt DL, Braunwald E, et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Eng J Med. 2013;369(14):1317–1326. doi: 10.1056/NEJMoa1307684White WB, Cannon CP, Heller SR, et al. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Eng J Med. 2013;369(14):1327–1335. doi: 10.1056/NEJMoa1305889White WB, Cannon CP, Heller SR, et al. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Eng J Med. 2013;369(14):1327–1335. doi: 10.1056/NEJMoa1305889Green JB, Bethel MA, Armstrong PW, et al. Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N Eng J Med. 2015;373(3):232–242. doi: 10.1056/NEJMoa1501352Green JB, Bethel MA, Armstrong PW, et al. Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N Eng J Med. 2015;373(3):232–242. doi: 10.1056/NEJMoa1501352Pfeffer MA, Claggett B, Diaz R, et al. Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N Eng J Med. 2015;373(23):2247–2257. doi: 10.1056/NEJMoa1509225Pfeffer MA, Claggett B, Diaz R, et al. Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N Eng J Med. 2015;373(23):2247–2257. doi: 10.1056/NEJMoa1509225Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Eng J Med. 2016;375(4):311–322. doi: 10.1056/NEJMoa1603827Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Eng J Med. 2016;375(4):311–322. doi: 10.1056/NEJMoa1603827Marso SP, Bain SC, Consoli A, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016;375(19):1834–1844. doi: 10.1056/NEJMoa1607141Marso SP, Bain SC, Consoli A, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016;375(19):1834–1844. doi: 10.1056/NEJMoa1607141Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Eng J Med. 2015;373(22):2117–2128. doi: 10.1056/NEJMoa1504720Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Eng J Med. 2015;373(22):2117–2128. doi: 10.1056/NEJMoa1504720Дедов И.И., Шестакова М.В. Феномен «метаболической памяти» в прогнозировании риска развития сосудистых осложнений при сахарном диабете // Терапевтический архив. – 2015. – Т. 87. – №10. – С. 4-10. [Dedov II, Shestakova MV. The metabolic memory phenomenon in predicting a risk for vascular complications in diabetes mellitus. Ter Arkh. 2015;87(10):4-10. doi: 10.17116/terarkh201587104-10Дедов И.И., Шестакова М.В. Феномен «метаболической памяти» в прогнозировании риска развития сосудистых осложнений при сахарном диабете // Терапевтический архив. – 2015. – Т. 87. – №10. – С. 4-10. [Dedov II, Shestakova MV. The metabolic memory phenomenon in predicting a risk for vascular complications in diabetes mellitus. Ter Arkh. 2015;87(10):4-10. doi: 10.17116/terarkh201587104-10Stratton IM, Adler AI, Neil HA, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000;321(7258):405-412. doi: 10.1136/bmj.321.7258.405Stratton IM, Adler AI, Neil HA, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000;321(7258):405-412. doi: 10.1136/bmj.321.7258.405Holman RR, Paul SK, Bethel MA, et al. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008; 359:1577-1589. doi: 10.1056/NEJMoa0806470Holman RR, Paul SK, Bethel MA, et al. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008; 359:1577-1589. doi: 10.1056/NEJMoa0806470Action to Control Cardiovascular Risk in Diabetes Study Group; Gerstein HC, Miller ME, Byington RP, et al. Effects of Intensive Glucose Lowering in Type 2 Diabetes. N Engl J Med. 2008;358(24):2545-2559. doi: 10.1056/NEJMoa0802743Action to Control Cardiovascular Risk in Diabetes Study Group; Gerstein HC, Miller ME, Byington RP, et al. Effects of Intensive Glucose Lowering in Type 2 Diabetes. N Engl J Med. 2008;358(24):2545-2559. doi: 10.1056/NEJMoa0802743Mita T, Katakami N, Yoshii H, et al. Alogliptin, a Dipeptidyl Peptidase 4 Inhibitor, Prevents the Progression of Carotid Atherosclerosis in Patients With Type 2 Diabetes: The Study of Preventive Effects of Alogliptin on Diabetic Atherosclerosis (SPEAD-A). Diabetes Care. 2016;39(1):139-148. doi: 10.2337/dc15-0781Mita T, Katakami N, Yoshii H, et al. Alogliptin, a Dipeptidyl Peptidase 4 Inhibitor, Prevents the Progression of Carotid Atherosclerosis in Patients With Type 2 Diabetes: The Study of Preventive Effects of Alogliptin on Diabetic Atherosclerosis (SPEAD-A). Diabetes Care. 2016;39(1):139-148. doi: 10.2337/dc15-0781Laiteerapong N, Karter AJ, Moffet HH, et al. Ten-year hemoglobin A1c trajectories and outcomes in type 2 diabetes mellitus: The Diabetes & Aging Study. J Diabetes Complications. 2017;31(1):94–100. doi: 10.1016/j.jdiacomp.2016.07.023Laiteerapong N, Karter AJ, Moffet HH, et al. Ten-year hemoglobin A1c trajectories and outcomes in type 2 diabetes mellitus: The Diabetes & Aging Study. J Diabetes Complications. 2017;31(1):94–100. doi: 10.1016/j.jdiacomp.2016.07.023Mearns ES, Sobieraj DM, White CM, et al. 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(4):e0125879. doi: 10.1371/journal.pone.0125879Mearns ES, Sobieraj DM, White CM, et al. 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(4):e0125879. doi: 10.1371/journal.pone.0125879Lingvay I. Sodium glucose cotransporter 2 and dipeptidyl peptidase-4 inhibition: promise of a dynamic duo. Endocr Pract. 2017;23(7): 831-840. doi: 10.4158/EP161725.RALingvay I. Sodium glucose cotransporter 2 and dipeptidyl peptidase-4 inhibition: promise of a dynamic duo. Endocr Pract. 2017;23(7): 831-840. doi: 10.4158/EP161725.RAScheen AJ. DPP-4 inhibitor plus SGLT-2 inhibitor as combination therapy for type 2 diabetes: from rationale to clinical aspects. Expert Opin Drug Metab Toxicol. 2016;12(12):1407-1417. doi: 10.1080/17425255.2016.1215427Scheen AJ. DPP-4 inhibitor plus SGLT-2 inhibitor as combination therapy for type 2 diabetes: from rationale to clinical aspects. Expert Opin Drug Metab Toxicol. 2016;12(12):1407-1417. doi: 10.1080/17425255.2016.1215427

The authors declare that there are no conflicts of interest present.