Early Combination Therapy with Oral Glucose-Lowering Agents in Type 2 Diabetes

Drugs

Volumn 77, Issue 3, 2017, Pages 247-264

  Bianchi, Cristina ^a   Daniele, Giuseppe ^a   Dardano, Angela ^a   Miccoli, Roberto ^a   Del Prato, Stefano ^a  

^a UNIVERSITY OF PISA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

2,4 THIAZOLIDINEDIONE DERIVATIVE; COLESEVELAM; DIPEPTIDYL PEPTIDASE IV INHIBITOR; GLUCOSE; HEMOGLOBIN A1C; METFORMIN; NATEGLINIDE; SODIUM GLUCOSE COTRANSPORTER 2 INHIBITOR; SULFONYLUREA DERIVATIVE; ANTIDIABETIC AGENT;

ABDOMINAL PAIN; ARTICLE; COMBINATION DRUG THERAPY; DIARRHEA; DISEASE COURSE; GASTROINTESTINAL SYMPTOM; GLUCOSE BLOOD LEVEL; GLYCEMIC CONTROL; HUMAN; HYPOGLYCEMIA; NAUSEA; NON INSULIN DEPENDENT DIABETES MELLITUS; SIDE EFFECT; TREATMENT OUTCOME; VOMITING; WEIGHT GAIN; DIABETES MELLITUS, TYPE 2; ORAL DRUG ADMINISTRATION;

ADMINISTRATION, ORAL; DIABETES MELLITUS, TYPE 2; DRUG THERAPY, COMBINATION; HUMANS; HYPOGLYCEMIC AGENTS;

EID: 85011634291     PISSN: 00126667     EISSN: 11791950     Source Type: Journal    
DOI: 10.1007/s40265-017-0694-4     Document Type: Article

References (97)

1. Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, Peters AL, Tsapas A, Wender R, Matthews DR. Management of hyperglycaemia in type 2 diabetes: 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;58:429–42.
2. 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;352:854–65.
3. Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, Hadden D, Turner RC, Holman RR. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000;321:405–12.
4. Thomsen RW, Baggesen LM, Svensson E, Pedersen L, Nørrelund H, Buhl ES, Haase CL, Johnsen SP. Early glycaemic control among patients with type 2 diabetes and initial glucose-lowering treatment: a 13-year population-based cohort study. Diabetes Obes Metab. 2015;17(8):771–80.
5. Cook MN, Girman CJ, Stein PP, Alexander CM. Initial monotherapy with either metformin or sulphonylureas often fails to achieve or maintain current glycaemic goals in patients with Type 2 diabetes in UK primary care. Diabet Med. 2007;24:350–8.
6. Matthews DR, Cull CA, Stratton IM, Holman RR, Turner RC, For the UK Prospective Diabetes Study Group. UKPDS 26: sulphonylurea failure in non-insulin-dependent diabetic patients over six years. Diabet Med. 1998;15:297–303.
7. Turner RC, Cull CA, Frighi V, Holman RR. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). UK Prospective Diabetes Study (UKPDS) Group. JAMA 1999;281(21):2005–2012.
8. Shah BR, Hux JE, Laupacis A, Zinman B, van Walraven C. Clinical inertia in response to inadequate glycemic control: do specialists differ from primary care physicians? Diabetes Care. 2005;28:600–6.
9. Brown JB, Nichols GA, Perry A. The burden of treatment failure in type 2 diabetes. Diabetes Care. 2004;27:1535–40.
10. Khunti K, Wolden ML, Thorsted BL, Andersen M, Davies MJ. Clinical inertia in people with type 2 diabetes: a retrospective cohort study of more than 80,000 people. Diabetes Care. 2013;36(11):3411–7.
11. DeFronzo RA, Eldor R, Abdul-Ghani M. Pathophysiologic approach to therapy in patients with newly diagnosed type 2 diabetes. Diabetes Care. 2013;36(Suppl. 2):S127–38.
12. DeFronzo RA. Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes. 2009;58:773–95.
13. Del Prato S, Felton AM, Munro N, Nesto R, Zimmet P, Zinman B, Global Partnership for Effective Diabetes Management. Improving glucose management: ten steps to get more patients with type 2 diabetes to glycaemic goal. Int J Clin Pract. 2005;59(11):1345–55.
14. Garber AJ, Abrahamson MJ, Barzilay JI, Blonde L, Bloomgarden ZT, Bush MA, Dagogo-Jack S, DeFronzo RA, Einhorn D, Fonseca VA, Garber JR, Garvey WT, Grunberger G, Handelsman Y, Henry RR, Hirsch IB, Jellinger PS, McGill JB, Mechanick JI, Rosenblit PD, Umpierrez GE, American Association of Clinical Endocrinologists (AACE).; American College of Endocrinology (ACE). Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm—2016 Executive summary. Endocr Pract. 2016;22(1):84–113.
15. Garber AJ, Donovan DS Jr, Dandona P, Bruce S, Park JS. Efficacy of glyburide/metformin tablets compared with initial monotherapy in type 2 diabetes. J Clin Endocrinol Metab. 2003;88:3598–604.
16. Garber AJ, Larsen J, Schneider SH, Piper BA, Henry D. Simultaneous glyburide/metformin therapy is superior to component monotherapy as an initial pharmacological treatment for type 2 diabetes. Diabetes Obes Metab. 2002;4(4):286. Diabetes Obes Metab. 2002;4(3):201–8.
17. Horton ES, Foley JE, Shen SG, Baron MA. Efficacy and tolerability of initial combination therapy with nateglinide and metformin in treatment-naive patients with type 2 diabetes. Curr Med Res Opin. 2004;20:883–9.
18. Schwarz SL, Gerich JE, Marcellari A, Jean-Louis L, Purkayastha D, Baron MA. Nateglinide, alone or in combination with metformin, is effective and well tolerated in treatment-naïve elderly patients with type 2 diabetes. Diabetes Obes Metab. 2008;10(8):652–60.
19. Gerich J, Raskin P, Jean-Louis L, Purkayastha D, Baron MA. PRESERVE-beta: two-year efficacy and safety of initial combination therapy with nateglinide or glyburide plus metformin. Diabetes Care. 2005;28(9):2093–9.
20. Ahrén B, Foley JE. Improved glucose regulation in type 2 diabetic patients with DPP-4 inhibitors: focus on alpha and beta cell function and lipid metabolism. Diabetologia. 2016;59(5):907–17.
21. Tella SH, Rendell MS. DPP-4 inhibitors: focus on safety. Expert Opin Drug Saf. 2015;14(1):127–40.
22. Viollet B, Foretz M. Revisiting the mechanisms of metformin action in the liver. Ann Endocrinol (Paris). 2013;74(2):123–9.
23. Hur KY, Lee MS. New mechanisms of metformin action: focusing on mitochondria and the gut. J Diabetes Investig. 2015;6(6):600–9.
24. Ross SA, Caballero AE, Del Prato S, Gallwitz B, Lewis-D’Agostino D, Bailes Z, Thiemann S, Patel S, Woerle HJ, von Eynatten M. Initial combination of linagliptin and metformin compared with linagliptin monotherapy in patients with newly diagnosed type 2 diabetes and marked hyperglycaemia: a randomized, double-blind, active-controlled, parallel group, multinational clinical trial. Diabetes Obes Metab. 2015;17:136–44.
25. Goldstein BJ, Feinglos MN, Lunceford JK, Johnson J, Williams-Herman DE, Sitagliptin 036 Study Group. Effect of initial combination therapy with sitagliptin, a dipeptidyl peptidase-4 inhibitor, and metformin on glycemic control in patients with type 2 diabetes. Diabetes Care. 2007;30(8):1979–87.
26. Williams-Herman D, Johnson J, Teng R, Luo E, Davies MJ, Kaufman KD, Goldstein BJ, Amatruda JM. Efficacy and safety of initial combination therapy with sitagliptin and metformin in patients with type 2 diabetes: a 54-week study. Curr Med Res Opin. 2009;25(3):569–83.
27. Williams-Herman D, Johnson J, Teng R, Golm G, Kaufman KD, Goldstein BJ, Amatruda JM. Efficacy and safety of sitagliptin and metformin as initial combination therapy and as monotherapy over 2 years in patients with type 2 diabetes. Diabetes Obes Metab. 2010;12:442–51.
28. Jadzinsky M, Pfützner A, Paz-Pacheco E, Xu Z, Allen E, Chen R, CV181-039 Investigators. Saxagliptin given in combination with metformin as initial therapy improves glycaemic control in patients with type 2 diabetes compared with either monotherapy: a randomized controlled trial. Diabetes Obes Metab. 2009;11(6):611–22.
29. Pfützner A, Paz-Pacheco E, Allen E, Frederich R, Chen R, CV181039 Investigators. Initial combination therapy with saxagliptin and metformin provides sustained glycaemic control and is well tolerated for up to 76 weeks. Diabetes Obes Metab. 2011;13(6):567–76.
30. Bosi E, Dotta F, Jia Y, Goodman M. Vildagliptin plus metformin combination therapy provides superior glycaemic control to individual monotherapy in treatment-naive patients with type 2 diabetes mellitus. Diabetes Obes Metab. 2009;11:506–15.
31. Olansky L, Reasner C, Seck TL, Williams-Herman DE, Chen M, Terranella L, Mehta A, Kaufman KD, Goldstein BJ. A treatment strategy implementing combination therapy with sitagliptin and metformin results in superior glycaemic control versus metformin monotherapy due to a low rate of addition of antihyperglycaemic agents. Diabetes Obes Metab. 2011;13(9):841–9.
32. Haak T, Meinicke T, Jones R, Weber S, von Eynatten M, Woerle HJ. Initial combination of linagliptin and metformin improves glycaemic control in type 2 diabetes: a randomized, double-blind, placebo-controlled study. Diabetes Obes Metab. 2012;14:565–74.
33. Haak T, Meinicke T, Jones R, Weber S, von Eynatten M, Woerle HJ. Initial combination of linagliptin and metformin in patients with type 2 diabetes: efficacy and safety in a randomised, double-blind 1-year extension study. Int J Clin Pract. 2013;67(12):1283–93.
34. Pratley RE, Fleck P, Wilson C. Efficacy and safety of initial combination therapy with alogliptin plus metformin versus either as monotherapy in drug-naïve patients with type 2 diabetes: a randomized, double-blind, 6-month study. Diabetes Obes Metab. 2014;16(7):613–21.
35. Wainstein J, Katz L, Engel SS, Xu L, Golm GT, Hussain S, O’Neill EA, Kaufman KD, Goldstein BJ. Initial therapy with the fixed-dose combination of sitagliptin and metformin results in greater improvement in glycaemic control compared with pioglitazone monotherapy in patients with type 2 diabetes. Diabetes Obes Metab. 2012;14(5):409–18.
36. Pérez-Monteverde A, Seck T, Xu L, Lee MA, Sisk CM, Williams-Herman DE, Engel SS, Kaufman KD, Goldstein BJ. Efficacy and safety of sitagliptin and the fixed-dose combination of sitagliptin and metformin vs. pioglitazone in drug-naïve patients with type 2 diabetes. Int J Clin Pract. 2011;65(9):930–8.
37. Reasner C, Olansky L, Seck TL, Williams-Herman DE, Chen M, Terranella L, Johnson-Levonas AO, Kaufman KD, Goldstein BJ. The effect of initial therapy with the fixed-dose combination of sitagliptin and metformin compared with metformin monotherapy in patients with type 2 diabetes mellitus. Diabetes Obes Metab. 2011;13(7):644–52.
38. Wu D, Li L, Liu C. Efficacy and safety of dipeptidyl peptidase-4 inhibitors and metformin as initial combination therapy and as monotherapy in patients with type 2 diabetes mellitus: a meta-analysis. Diabetes Obes Metab. 2014;16:30–7.
39. Staels B, Handelsman Y, Fonseca V. Bile acid sequestrants for lipid and glucose control. Curr Diab Rep. 2010 ;10(1), pp. 70–7, doi:10.1007/s11892-009-0087-5
40. Rosenstock J, Fonseca VA, Garvey WT, Goldberg RB, Handelsman Y, Abby SL, Lai YL, Jin X, Misir S, Nagendran S, Jones MR. Initial combination therapy with metformin and colesevelam for achievement of glycemic and lipid goals in early type 2 diabetes. Endocr Pract. 2010;16(4):629–40.
41. Rosenstock J, Hernandez-Triana E, Handelsman Y, Misir S, Jones MR, Nagendran S. Initial combination therapy with metformin plus colesevelam in drug-naïve Hispanic patients with early type 2 diabetes. Postgrad Med. 2012;124(4):7–13.
42. Natali A, Ferrannini E. Effects of metformin and thiazolidinediones on suppression of hepatic glucose production and stimulation of glucose uptake in type 2 diabetes: a systematic review. Diabetologia. 2006;49(3):434–41.
43. Chou HS, Palmer JP, Jones AR, Waterhouse B, Ferreira-Cornwell C, Krebs J, Goldstein BJ. Initial treatment with fixed-dose combination rosiglitazone/glimepiride in patients with previously untreated type 2 diabetes. Diabetes Obes Metab. 2008;10:626–37.
44. Rosenstock J, Kim SW, Baron MA, Camisasca RP, Cressier F, Couturier A, Dejager S. Efficacy and tolerability of initial combination therapy with vildagliptin and pioglitazone compared with component monotherapy in patients with type 2 diabetes. Diabetes Obes Metab. 2007;9(2):175–85.
45. Rosenstock J, Inzucchi SE, Seufert J, Fleck PR, Wilson CA, Mekki Q. Initial combination therapy with alogliptin and pioglitazone in drug-naïve patients with type 2 diabetes. Diabetes Care. 2010;33(11):2406–8.
46. Van Raalte DH, van Genugten RE, Eliasson B, Möller-Goede DL, Mari A, Tura A, Wilson C, Fleck P, Taskinen MR, Smith U, Diamant M. The effect of alogliptin and pioglitazone combination therapy on various aspects of β-cell function in patients with recent-onset type 2 diabetes. Eur J Endocrinol. 2014;170(4):565–74.
47. Gomis R, Espadero RM, Jones R, Woerle HJ, Dugi KA. Efficacy and safety of initial combination therapy with linagliptin and pioglitazone in patients with inadequately controlled type 2 diabetes: a randomized, double-blind, placebo-controlled study. Diabetes Obes Metab. 2011;13(7):653–61.
48. Kahn SE, Haffner SM, Heise MA, Herman WH, Holman RR, Jones NP, Kravitz BG, Lachin JM, O’Neill MC, Zinman B, Viberti G, ADOPT Study Group. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med. 2006;355(23):2427–43.
49. Yoon KH, Shockey GR, Teng R, Golm GT, Thakkar PR, Meehan AG, Williams-Herman DE, Kaufman KD, Amatruda JM, Steinberg H. Effect of initial combination therapy with sitagliptin, a dipeptidyl peptidase-4 inhibitor, and pioglitazone on glycemic control and measures of β-cell function in patients with type 2 diabetes. Int J Clin Pract. 2011;65(2):154–64.
50. Yoon KH, Steinberg H, Teng R, Golm GT, Lee M, O’Neill EA, Kaufman KD, Goldstein BJ. Efficacy and safety of initial combination therapy with sitagliptin and pioglitazone in patients with type 2 diabetes: a 54-week study. Diabetes Obes Metab. 2012;14(8):745–52.
51. Rosenstock J, Rood J, Cobitz A, Biswas N, Chou H, Garber A. Initial treatment with rosiglitazone/metformin fixed-dose combination therapy compared with monotherapy with either rosiglitazone or metformin in patients with uncontrolled type 2 diabetes. Diabetes Obes Metab. 2006;8:650–60.
52. Borges JL, Bilezikian JP, Jones-Leone AR, et al. A randomised, parallel group, double-blind, multicentre study comparing the efficacy and safety of Avandamet (rosiglitazone/metformin) and metformin on long-term glycaemic control and bone mineral density after 80 weeks of treatment in drug-naive type 2 diabetes mellitus patients. Diabetes Obes Metab. 2011;13:1036–46.
53. Perez A, Zhao Z, Jacks R, Spanheimer R. Efficacy and safety of pioglitazone/metformin fixed-dose combination therapy compared with pioglitazone and metformin monotherapy in treating patients with T2DM. Curr Med Res Opin. 2009;25:2915–23.
54. Ferrannini E, Muscelli E, Frascerra S, Baldi S, Mari A, Heise T, Broedl UC, Woerle HJ. Metabolic response to sodium-glucose cotransporter 2 inhibition in type 2 diabetic patients. J Clin Invest. 2014;124(2):499–508.
55. Neschen S, Scheerer M, Seelig A, Huypens P, Schultheiss J, Wu M, Wurst W, Rathkolb B, Suhre K, Wolf E, Beckers J, Hrabé de Angelis M. Metformin supports the antidiabetic effect of a sodium glucose cotransporter 2 inhibitor by suppressing endogenous glucose production in diabetic mice. Diabetes. 2015;64(1):284–90.
56. 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(5):446–56.
57. Hadjadj S, Rosenstock J, Mainicke T, Woerle HJ, Broedl UC. Initial combination of empagliflozin and metformin in patients with type 2 diabetes. Diabetes Care. 2016;39(10):1718–28.
58. Rosenstock J, Chuck L, González-Ortiz M, Merton K, Craig J, Capuano G, Qiu R. Initial combination therapy with canagliflozin plus metformin versus each component as monotherapy for drug-naïve type 2 diabetes. Diabetes Care. 2016;39(3):353–62.
59. Rosenstock J, Vico M, Wei L, Salsali A, List JF. Effects of dapagliflozin, an SGLT2 inhibitor, on HbA(1c), body weight, and hypoglycemia risk in patients with type 2 diabetes inadequately controlled on pioglitazone monotherapy. Diabetes Care. 2012;35(7):1473–8.
60. Kovacs CS, Seshiah V, Swallow R, Jones R, Rattunde H, Woerle HJ, Broedl UC, EMPA-REG PIO™ trial investigators. Empagliflozin improves glycaemic and weight control as add-on therapy to pioglitazone or pioglitazone plus metformin in patients with type 2 diabetes: a 24-week, randomized, placebo-controlled trial. Diabetes Obes Metab. 2014;16(2):147–58.
61. Lewin A, DeFronzo RA, Patel S, Liu D, Kaste R, Woerle HJ, Broedl UC. Initial combination of empagliflozin and linagliptin in subjects with type 2 diabetes. Diabetes Care. 2015;38:394–402.
62. Phung OJ, Scholle JM, Talwar M, Coleman CI. Effect of noninsulin antidiabetic drugs added to metformin therapy on glycemic control, weight gain, and hypoglycemia in type 2 diabetes. JAMA. 2010;303(14):1410–8.
63. 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(5):410–7.
64. Avogaro A, Fadini GP, Sesti G, Bonora E, Del Prato S. Continued effort to translate cardiovascular outcome trials into clinical practice. Cardiovasc Diabetol. 2016;15(1):111.
65. Nathan DM, Buse JB, Kahn SE, Krause-Steinrauf H, Larkin ME, Staten M, Wexler D, Lachin JM, GRADE Study Research Group. Rationale and design of the glycemia reduction approaches in diabetes: a comparative effectiveness study (GRADE). Diabetes Care. 2013;36(8):2254–61.
66. Abdul-Ghani MA, Puckett C, Triplitt C, Maggs D, Adams J, Cersosimo E, DeFronzo RA. 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;17:268–75.
67. Zinman B, Harris SB, Neuman J, Gerstein HC, Retnakaran RR, Raboud J, Qi Y, Hanley AJ. Low-dose combination therapy with rosiglitazone and metformin to prevent type 2 diabetes mellitus (CANOE trial): a double-blind randomised controlled study. Lancet. 2010;376(9735):103–11.
68. Scheen AJ. DPP-4 inhibitors plus SGLT-2 inhibitor as combination therapy for type 2 diabetes: from rationale to to clinical aspects. Expert Opin Drug Metab Toxicol. 2016;12(12):1407–17.
69. Wu D, Li L, Liu C. Efficacy and safety of dipeptidyl peptidase-4 inhibitors and metformin as initial combination therapy and as monotherapy in patients with type 2 diabetes mellitus: a meta-analysis. Diabetes Obes Metab. 2014;16(1):30–7.
70. Palmer SC, Mavridis D, Nicolucci A, Johnson DW, Tonelli M, Craig JC, Maggo J, Gray V, De Berardis G, Ruospo M, Natale P, Saglimbene V, Badve SV, Cho Y, Nadeau-Fredette AC, Burke M, Faruque L, Lloyd A, Ahmad N, Liu Y, Tiv S, Wiebe N, Strippoli GF. Comparison of clinical outcomes and adverse events associated with glucose-lowering drugs in patients with type 2 diabetes: a meta-analysis. JAMA. 2016;316(3):313–24.
71. Capoccia K, Odegard PS, Letassy N. Medication adherence with diabetes medication: a systematic review of the literature. Diabetes Educ. 2016;42(1):34–71.
72. Claxton AJ, Cramer J, Pierce C. A systematic review of the associations between dose regimens and medication compliance. Clin Ther. 2001;23(8):1296–310.
73. Rozenfeld Y, Hunt JS, Plauschinat C, Wong KS. Oral antidiabetic medication adherence and glycemic control in managed care. Am J Manag Care. 2008;14(2):71–5.
74. Li J, Lian H. Recent development of single preparations and fixed-dose combination tablets for the treatment of non-insulin-dependent diabetes mellitus: a comprehensive summary for antidiabetic drugs. Arch Pharm Res. 2016;39(6):731–46.
75. Han S, Iglay K, Davies MJ, Zhang Q, Radican L. Glycemic effectiveness and medication adherence with fixed-dose combination or coadministered dual therapy of antihyperglycemic regimens: a meta-analysis. Curr Med Res Opin. 2012;28(6):969–77.
76. Del Prato S, Marchetti P, Bonadonna RC. Phasic insulin release and metabolic regulation in type 2 diabetes. Diabetes. 2002;51(Suppl. 1):S109–16.
77. Prospective UK, Diabetes Study Group. U.K. prospective diabetes study 16. Overview of 6 years’ therapy of type II diabetes: a progressive disease. Diabetes. 1995;44:1249–58.
78. Festa A, Williams K, D’Agostino R Jr, Wagenknecht LE, Haffner SM. The natural course of β-cell function in nondiabetic and diabetic individuals: the Insulin Resistance Atherosclerosis Study. Diabetes. 2006;55:1114–20.
79. Drucker DJ. The biology of incretin hormones. Cell Metab. 2006;3:153–65.
80. Dhillon S. Sitagliptin: a review of its use in the management of type 2 diabetes mellitus. Drugs. 2010;70:489–512.
81. Foley JE, Bunck MC, Möller-Goede DL, Poelma M, Nijpels G, Eekhoff EM, Schweizer A, Heine RJ, Diamant M. Beta cell function following 1 year vildagliptin or placebo treatment and after 12 week washout in drug-naive patients with type 2 diabetes and mild hyperglycaemia: a randomised controlled trial. Diabetologia. 2011;54(8):1985–91.
82. Heise T, Larbig M, Patel S, Seck T, Hehnke U, Woerle HJ, Dugi K. The dipeptidyl peptidase-4 inhibitor linagliptin lowers postprandial glucose and improves measures of β-cell function in type 2 diabetes. Diabetes Obes Metab. 2014;16(10):1036–9.
83. Mannucci E, Ognibene A, Cremasco F, et al. Effect of metformin on glucagon-like peptide 1 (GLP-1) and leptin levels in obese nondiabetic subjects. Diabetes Care. 2001;24:489–94.
84. Williams-Herman D, Xu L, Teng R, Golm GT, Johnson J, Davies MJ, Kaufman KD, Goldstein BJ. Effect of initial combination therapy with sitagliptin and metformin on β-cell function in patients with type 2 diabetes. Diabetes Obes Metab. 2012;14(1):67–76.
85. Kahn SE, Lachin JM, Zinman B, Haffner SM, Aftring RP, Paul G, Kravitz BG, Herman WH, Viberti G, Holman RR, ADOPT Study Group. Effects of rosiglitazone, glyburide, and metformin on β-cell function and insulin sensitivity in ADOPT. Diabetes. 2011;60(5):1552–60.
86. Lupi R, Del Guerra S, Marselli L, Bugliani M, Boggi U, Mosca F, Marchetti P, Del Prato S. Rosiglitazone prevents the impairment of human islet function induced by fatty acids: evidence for a role of PPARgamma2 in the modulation of insulin secretion. Am J Physiol Endocrinol Metab. 2004;286(4):E560–7.
87. Del Prato S, Nauck M, Durán-Garcia S, Maffei L, Rohwedder K, Theuerkauf A, Parikh S. 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(6):581–90.
88. Del Prato S, Foley JE, Kothny W, Kozlovski P, Stumvoll M, Paldánius PM, Matthews DR. Study to determine the durability of glycaemic control with early treatment with a vildagliptin-metformin combination regimen vs. standard-of-care metformin monotherapy-the VERIFY trial: a randomized double-blind trial. Diabet Med. 2014;31(10):1178–84.
89. 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(9139):1558. Lancet. 1998;352(9139):1558.
90. Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, Mattheus M, Devins T, Johansen OE, Woerle HJ, Broedl UC, Inzucchi SE, EMPA-REG OUTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117–28.
91. Wanner C, Inzucchi SE, Lachin JM, Fitchett D, von Eynatten M, Mattheus M, Johansen OE, Woerle HJ, Broedl UC, Zinman B, EMPA-REG OUTCOME Investigators. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med. 2016;375(4):323–34.
92. Neal B, Perkovic V, de Zeeuw D, Mahaffey KW, Fulcher G, Stein P, Desai M, Shaw W, Jiang J, Vercruysse F, Meininger G, Matthews D. Rationale, design, and baseline characteristics of the Canagliflozin Cardiovascular Assessment Study (CANVAS)—a randomized placebo-controlled trial. Am Heart J. 2013;166(2):217–23.
93. Multicenter Trial to Evaluate the Effect of Dapagliflozin on the Incidence of Cardiovascular Events (DECLARE-TIMI58). https://clinicaltrials.gov/ct2/show/NCT01730534?term=dapagliflozin+cardiovascular&cond=%22Myocardial+Infarction%22&rank=1. Accessed 20 Dec 2016.
94. Cahn A, Cefalu WT. Clinical considerations for use of initial combination therapy in type 2 diabetes. Diabetes Care. 2016;39(Suppl 2):S137–45.
95. Raz I, Riddle MC, Rosenstock J, Buse JB, Inzucchi SE, Home PD, Del Prato S, Ferrannini E, Chan JC, Leiter LA, Leroith D, Defronzo R, Cefalu WT. Personalized management of hyperglycemia in type 2 diabetes: reflections from a Diabetes Care Editors’ Expert Forum. Diabetes Care. 2013;36(6):1779–88.
96. Lyssenko V, Bianchi C, Del Prato S. Personalized therapy by phenotype and genotype. Diabetes Care. 2016;39(Suppl 2):S127–36.
97. Scheen AJ. Precision medicine: the future in diabetes care? Diabetes Res Clin Pract. 2016;117:12–21.