684
Views
10
CrossRef citations to date
0
Altmetric
Reviews

Clinical use of dipeptidyl peptidase-4 and sodium-glucose cotransporter 2 inhibitors in combination therapy for type 2 diabetes mellitus

Pages 463-479 | Received 01 Apr 2015, Accepted 21 Apr 2015, Published online: 08 May 2015

References

  • American Diabetes Association . Fast facts: data and statistics about diabetes. Available from http://professional.diabetes.org/admin/UserFiles/0%20-%20Sean/14_fast_facts.pdf. Last accessed 16 March 2015
  • 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
  • Centers for Disease Control and Prevention . National diabetes statistics report: estimates of diabetes and its burden in the United States. 2014. Available from http://www.cdc.gov/diabetes/pubs/statsreport14/national-diabetes-report-web.pdf. Last accessed 16 March 2015
  • American Diabetes Association . Standards of medical care in diabetes-2015. Diabetes Care 2015;38:S1–94
  • Garber AJ , Abrahamson MJ , Barzilay JI , Blonde L , Bloomgarden ZT , Bush MA , et al. American Association of Clinical Endocrinologists’ comprehensive diabetes management algorithm 2013 consensus statement--executive summary. Endocr Pract 2013;19:536–57
  • Glucophage® (metformin) . Full Prescribing Information, Bristol-Myers Squibb Company. Princeton, NJ: 2009
  • DeFronzo RA , Goodman AM . Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. The Multicenter Metformin Study Group. N Engl J Med 1995;333:541–9
  • Neumiller JJ , Wood L , Campbell RK . Dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes mellitus. Pharmacotherapy 2010;30:463–84
  • Drucker DJ . Enhancing incretin action for the treatment of type 2 diabetes. Diabetes Care 2003;26:2929–40
  • Wilding JP , Hardy K . Glucagon-like peptide-1 analogues for type 2 diabetes. BMJ 2011;342:d410
  • Calanna S , Christensen M , Holst JJ , Laferrère B , Gluud LL , Vilsbøll T , Knop FK . Secretion of glucagon-like peptide-1 in patients with type 2 diabetes mellitus: systematic review and meta-analyses of clinical studies. Diabetologia 2013;56:965–72
  • Toft-Nielsen MB , Damholt MB , Madsbad S , Hilsted LM , Hughes TE , Michelsen BK , Holst JJ . Determinants of the impaired secretion of glucagon-like peptide-1 in type 2 diabetic patients. J Clin Endocrinol Metab 2001;86:3717–23
  • Kjems LL , Holst JJ , Volund A , Madsbad S . The influence of GLP-1 on glucose-stimulated insulin secretion: effects on beta-cell sensitivity in type 2 and nondiabetic subjects. Diabetes 2003;52:380–6
  • Nisal K , Kela R , Khunti K , Davies MJ . Comparison of efficacy between incretin-based therapies for type 2 diabetes mellitus. BMC Med 2012;10:152
  • Mathieu C . The scientific evidence: vildagliptin and the benefits of islet enhancement. Diabetes Obes Metab 2009;11:9–17
  • Poucher SM , Cheetham S , Francis J , Zinker B , Kirby M , Vickers SP . Effects of saxagliptin and sitagliptin on glycaemic control and pancreatic beta-cell mass in a streptozotocin-induced mouse model of type 2 diabetes. Diabetes Obes Metab 2012;14:918–26
  • Craddy P , Palin HJ , Johnson KI . Comparative effectiveness of dipeptidylpeptidase-4 inhibitors in type 2 diabetes: a systematic review and mixed treatment comparison. Diabetes Ther 2014;5:1–41
  • Nauck MA . Update on developments with SGLT2 inhibitors in the management of type 2 diabetes. Drug Des Devel Ther 2014;8:1335–80
  • Rahmoune H , Thompson PW , Ward JM , Smith CD , Hong G , Brown J . Glucose transporters in human renal proximal tubular cells isolated from the urine of patients with non-insulin-dependent diabetes. Diabetes 2005;54:3427–34
  • Kasichayanula S , Chang M , Hasegawa M , Liu X , Yamahira N , LaCreta FP , et al. Pharmacokinetics and pharmacodynamics of dapagliflozin, a novel selective inhibitor of sodium-glucose co-transporter type 2, in Japanese subjects without and with type 2 diabetes mellitus. Diabetes Obes Metab 2011;13:357–65
  • Ferrannini E , Ramos SJ , Salsali A , Tang W , List JF . Dapagliflozin monotherapy in type 2 diabetic patients with inadequate glycemic control by diet and exercise: a randomized, double-blind, placebo-controlled, phase 3 trial. Diabetes Care 2010;33:2217–24
  • Nauck MA , Ellis GC , Fleck PR , Wilson CA , Mekki Q ; Alogliptin Study 008 Group . Efficacy and safety of adding the dipeptidyl peptidase-4 inhibitor alogliptin to metformin therapy in patients with type 2 diabetes inadequately controlled with metformin monotherapy: a multicentre, randomised, double-blind, placebo-controlled study. Int J Clin Pract 2009;63:46–55
  • 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;16:1239–46
  • Pratley RE , Kipnes MS , Fleck PR , Wilson C , Mekki Q ; Alogliptin Study 007 Group . Efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin in patients with type 2 diabetes inadequately controlled by glyburide monotherapy. Diabetes Obes Metab 2009;11:167–76
  • Pratley RE , Fleck P , Wilson C . Efficacy and safety of initial combination therapy with alogliptin plus metformin versus either as monotherapy in drug-naive patients with type 2 diabetes: a randomized, double-blind, 6-month study. Diabetes Obes Metab 2014;16:613–21
  • Rosenstock J , Inzucchi SE , Seufert J , Fleck PR , Wilson CA , Mekki Q . Initial combination therapy with alogliptin and pioglitazone in drug-naive patients with type 2 diabetes. Diabetes Care 2010;33:2406–8
  • DeFronzo RA , Burant CF , Fleck P , Wilson C , Mekki Q , Pratley RE . Efficacy and tolerability of the DPP-4 inhibitor alogliptin combined with pioglitazone, in metformin-treated patients with type 2 diabetes. J Clin Endocrinol Metab 2012;97:1615–22
  • Bosi E , Ellis GC , Wilson CA , Fleck PR . Alogliptin as a third oral antidiabetic drug in patients with type 2 diabetes and inadequate glycaemic control on metformin and pioglitazone: a 52-week, randomized, double-blind, active-controlled, parallel-group study. Diabetes Obes Metab 2011;13:1088–96
  • Rosenstock J , Rendell MS , Gross JL , Fleck PR , Wilson CA , Mekki Q . Alogliptin added to insulin therapy in patients with type 2 diabetes reduces HbA1C without causing weight gain or increased hypoglycaemia. Diabetes Obes Metab 2009;11:1145–52
  • Pratley RE , Reusch JE , Fleck PR , Wilson CA , Mekki Q ; Alogliptin Study 009 Group . Efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin added to pioglitazone in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled study. Curr Med Res Opin 2009;25:2361–71
  • 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
  • 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;13:653–61
  • Taskinen MR , Rosenstock J , Tamminen I , Kubiak R , Patel S , Dugi KA , Woerle HJ . Safety and efficacy of linagliptin as add-on therapy to metformin in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled study. Diabetes Obes Metab 2011;13:65–74
  • Gallwitz B , Rosenstock J , Rauch T , Bhattacharya S , Patel S , von Eynatten M , et al. 2-year efficacy and safety of linagliptin compared with glimepiride in patients with type 2 diabetes inadequately controlled on metformin: a randomised, double-blind, non-inferiority trial. Lancet 2012;380:475–83
  • Bajaj M , Gilman R , Patel S , Kempthorne-Rawson J , Lewis-D’Agostino D , Woerle HJ . Linagliptin improved glycaemic control without weight gain or hypoglycaemia in patients with type 2 diabetes inadequately controlled by a combination of metformin and pioglitazone: a 24-week randomized, double-blind study. Diabet Med 2014;31:1505–14
  • Owens DR , Swallow R , Dugi KA , Woerle HJ . Efficacy and safety of linagliptin in persons with type 2 diabetes inadequately controlled by a combination of metformin and sulphonylurea: a 24-week randomized study. Diabet Med 2011;28:1352–61
  • Yki-Jarvinen H , Rosenstock J , Duran-Garcia S , Pinnetti S , Bhattacharya S , Thiemann S , et al. Effects of adding linagliptin to basal insulin regimen for inadequately controlled type 2 diabetes: a ≥52-week randomized, double-blind study. Diabetes Care 2013;36:3875–81
  • Barnett AH , Huisman H , Jones R , von Eynatten M , Patel S , Woerle HJ . Linagliptin for patients aged 70 years or older with type 2 diabetes inadequately controlled with common antidiabetes treatments: a randomised, double-blind, placebo-controlled trial. Lancet 2013;382:1413–23
  • DeFronzo RA , Hissa MN , Garber AJ , Luiz Gross J , Yuyan Duan R , Ravichandran S , et al. The efficacy and safety of saxagliptin when added to metformin therapy in patients with inadequately controlled type 2 diabetes with metformin alone. Diabetes Care 2009;32:1649–55
  • Jadzinsky M , Pfutzner 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;11:611–22
  • Yang W , Pan CY , Tou C , Zhao J , Gause-Nilsson I . Efficacy and safety of saxagliptin added to metformin in Asian people with type 2 diabetes mellitus: a randomized controlled trial. Diabetes Res Clin Pract 2011;94:217–24
  • Goke B , Gallwitz B , Eriksson J , Hellqvist A , Gause-Nilsson I ; D1680C00001 Investigators . Saxagliptin is non-inferior to glipizide in patients with type 2 diabetes mellitus inadequately controlled on metformin alone: a 52-week randomised controlled trial. Int J Clin Pract 2010;64:1619–31
  • Chacra AR , Tan GH , Apanovitch A , Ravichandran S , List J , Chen R ; CV181-040 Investigators . Saxagliptin added to a submaximal dose of sulphonylurea improves glycaemic control compared with uptitration of sulphonylurea in patients with type 2 diabetes: a randomised controlled trial. Int J Clin Pract 2009;63:1395–406
  • Hollander P , Li J , Allen E , Chen R ; CV181-013 Investigators . Saxagliptin added to a thiazolidinedione improves glycemic control in patients with type 2 diabetes and inadequate control on thiazolidinedione alone. J Clin Endocrinol Metab 2009;94:4810–9
  • Barnett AH , Charbonnel B , Donovan M , Fleming D , Chen R . Effect of saxagliptin as add-on therapy in patients with poorly controlled type 2 diabetes on insulin alone or insulin combined with metformin. Curr Med Res Opin 2012;28:513–23
  • Moses RG , Kalra S , Brook D , Sockler J , Monyak J , Visvanathan J , 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;16:443–50
  • Charbonnel B , Karasik A , Liu J , Wu M , Meininger G ; Sitagliptin Study 020 Group . Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes inadequately controlled with metformin alone. Diabetes Care 2006;29:2638–43
  • 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;30:1979–87
  • Nauck MA , Meininger G , Sheng D , Terranella L , Stein PP ; Sitagliptin Study 024 Group . Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, compared with the sulfonylurea, glipizide, in patients with type 2 diabetes inadequately controlled on metformin alone: a randomized, double-blind, non-inferiority trial. Diabetes Obes Metab 2007;9:194–205
  • Rosenstock J , Brazg R , Andryuk PJ , Lu K , Stein P ; Sitagliptin Study 019 Group . Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing pioglitazone therapy in patients with type 2 diabetes: a 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Clin Ther 2006;28:1556–68
  • Hermansen K , Kipnes M , Luo E , Fanurik D , Khatami H , Stein P ; Sitagliptin Study 035 Group . Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, in patients with type 2 diabetes mellitus inadequately controlled on glimepiride alone or on glimepiride and metformin. Diabetes Obes Metab 2007;9:733–45
  • Vilsboll T , Rosenstock J , Yki-Jarvinen H , Cefalu WT , Chen Y , Luo E , et al. Efficacy and safety of sitagliptin when added to insulin therapy in patients with type 2 diabetes. Diabetes Obes Metab 2010;12:167–77
  • Fonseca V , Staels B , Morgan JD 2nd , Shentu Y , Golm GT , Johnson-Levonas AO , et al. Efficacy and safety of sitagliptin added to ongoing metformin and pioglitazone combination therapy in a randomized, placebo-controlled, 26-week trial in patients with type 2 diabetes. J Diabetes Complications 2013;27:177–83
  • Onglyza® (saxagliptin) . Full Prescribing Information, Bristol-Myers Squibb and AstraZeneca Pharmaceuticals LP. Princeton, NJ, and Wilmington, DE: 2014
  • Januvia® (sitagliptin) . Full Prescribing Information, Merck. Whitehouse Station, NJ: 2015
  • Tradjenta® (linagliptin) . Full Prescribing Information, Boehringer Ingelheim. Ridgefield, CT: 2014
  • Nesina® (alogliptin) . Full Prescribing Information. Takeda Pharmaceuticals America, Inc; Deerfield, IL: 2013
  • Lavalle-Gonzalez FJ , Januszewicz A , Davidson J , Tong C , Qiu R , Canovatchel W , Meininger G . Efficacy and safety of canagliflozin compared with placebo and sitagliptin in patients with type 2 diabetes on background metformin monotherapy: a randomised trial. Diabetologia 2013;56:2582–92
  • Cefalu WT , Leiter LA , Yoon KH , Arias P , Niskanen L , Xie J , et al. Efficacy and safety of canagliflozin versus glimepiride in patients with type 2 diabetes inadequately controlled with metformin (CANTATA-SU): 52 week results from a randomised, double-blind, phase 3 non-inferiority trial. Lancet 2013;382:941–50
  • Schernthaner G , Gross JL , Rosenstock J , Guarisco M , Fu M , Yee J , et al. Canagliflozin compared with sitagliptin for patients with type 2 diabetes who do not have adequate glycemic control with metformin plus sulfonylurea: a 52-week randomized trial. Diabetes Care 2013;36:2508–15
  • Wilding JP , Charpentier G , Hollander P , González-Gálvez G , Mathieu C , Vercruysse F , et al. Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin and sulphonylurea: a randomised trial. Int J Clin Pract 2013;67:1267–82
  • Forst T , Guthrie R , Goldenberg R , Yee J , Vijapurkar U , Meininger G , Stein P . Efficacy and safety of canagliflozin over 52 weeks in patients with type 2 diabetes on background metformin and pioglitazone. Diabetes Obes Metab 2014;16:467–77
  • Bode B , Stenlof K , Sullivan D , Fung A , Usiskin K . Efficacy and safety of canagliflozin treatment in older subjects with type 2 diabetes mellitus: a randomized trial. Hosp Pract (1995) 2013;41:72–84
  • Yale JF , Bakris G , Cariou B , Yue D , David-Neto E , Xi L , et al. Efficacy and safety of canagliflozin in subjects with type 2 diabetes and chronic kidney disease. Diabetes Obes Metab 2013;15:463–73
  • Bailey CJ , Gross JL , Pieters A , Bastien A , List JF . Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with metformin: a randomised, double-blind, placebo-controlled trial. Lancet 2010;375:2223–33
  • 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;66:446–56
  • Nauck MA , Del Prato S , Meier JJ , Durán-García S , Rohwedder K , Elze M , Parikh SJ . Dapagliflozin versus glipizide as add-on therapy in patients with type 2 diabetes who have inadequate glycemic control with metformin: a randomized, 52-week, double-blind, active-controlled noninferiority trial. Diabetes Care 2011;34:2015–22
  • Rosenstock J , Vico M , Wei L , Salsali A , List JF . Effects of dapagliflozin, an SGLT2 inhibitor, on HbA1c, body weight, and hypoglycemia risk in patients with type 2 diabetes inadequately controlled on pioglitazone monotherapy. Diabetes Care 2012;35:1473–8
  • Strojek K , Yoon KH , Hruba V , Elze M , Langkilde AM , Parikh S . Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with glimepiride: a randomized, 24-week, double-blind, placebo-controlled trial. Diabetes Obes Metab 2011;13:928–38
  • Rosenstock J , Hansen L , Zee P , Li Y , Cook W , Hirshberg B , Iqbal N . Dual add-on therapy in type 2 diabetes poorly controlled with metformin monotherapy: a randomized double-blind trial of saxagliptin plus dapagliflozin addition versus single addition of saxagliptin or dapagliflozin to metformin. Diabetes Care 2015;38:376–83
  • Jabbour SA , Hardy E , Sugg J , Parikh S ; Study 10 Group . Dapagliflozin is effective as add-on therapy to sitagliptin with or without metformin: a 24-week, multicenter, randomized, double-blind, placebo-controlled study. Diabetes Care 2014;37:740–50
  • Wilding JP , Woo V , Soler NG , Pahor A , Sugg J , Rohwedder K , et al. Long-term efficacy of dapagliflozin in patients with type 2 diabetes mellitus receiving high doses of insulin: a randomized trial. Ann Intern Med 2012;156:405–15
  • Matthaei S , Bowering K , Rohwedder K , Grohl A , Parikh S ; Study 05 Group . Dapagliflozin improves glycemic control and reduces body weight as add-on therapy to metformin plus sulfonylurea: a 24-week randomized, double-blind clinical trial. Diabetes Care 2015;38:365–72
  • Leiter LA , Cefalu WT , de Bruin TW , Gause-Nilsson I , Sugg J , Parikh SJ . Dapagliflozin added to usual care in individuals with type 2 diabetes mellitus with preexisting cardiovascular disease: a 24-week, multicenter, randomized, double-blind, placebo-controlled study with a 28-week extension. J Am Geriatr Soc 2014;62:1252–62
  • Kohan DE , Fioretto P , Tang W , List JF . Long-term study of patients with type 2 diabetes and moderate renal impairment shows that dapagliflozin reduces weight and blood pressure but does not improve glycemic control. Kidney Int 2014;85:962–71
  • Häring HU , Merker L , Seewaldt-Becker E , Weimer M , Meinicke T , Broedl UC , et al. Empagliflozin as add-on to metformin in patients with type 2 diabetes: a 24-week, randomized, double-blind, placebo-controlled trial. Diabetes Care 2014;37:1650–9
  • Ridderstrale 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 randomised, active-controlled, double-blind, phase 3 trial. Lancet Diabetes Endocrinol 2014;2:691–700
  • Lewin A , DeFronzo R , 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
  • Haring HU , Merker L , Seewaldt-Becker E , Weimer M , Meinicke T , Woerle HJ , et al. Empagliflozin as add-on to metformin plus sulfonylurea in patients with type 2 diabetes: a 24-week, randomized, double-blind, placebo-controlled trial. Diabetes Care 2013;36:3396–404
  • Kovacs CS , Seshiah V , Swallow R , Jones R , Rattunde H , Woerle HJ , et al. 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;16:147–58
  • DeFronzo RA , Lewin A , Patel S , Liu D , Kaste R , Woerle HJ , Broedl UC . Combination of empagliflozin and linagliptin as second-line therapy in subjects with type 2 diabetes inadequately controlled on metformin. Diabetes Care 2015;38:384–93
  • Barnett AH , Mithal A , Manassie J , Jones R , Rattunde H , Woerle HJ , et al. Efficacy and safety of empagliflozin added to existing antidiabetes treatment in patients with type 2 diabetes and chronic kidney disease: a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol 2014;2:369–84
  • Farxiga® (dapagliflozin) . Full Prescribing Information, Bristol-Myers Squibb and AstraZeneca. Princeton, NJ, and Wilmington, DE: 2015
  • Jardiance® (empagliflozin) . Full Prescribing Information, Boehringer Ingelheim Pharmaceuticals and Eli Lilly and Company. Ingelheim, Germany, and Indianapolis, IN: 2014
  • Invokana® (canagliflozin) . Full Prescribing Information. Janssen Pharmaceuticals; Titusville, NJ: 2015
  • Multicenter trial to evaluate the effect of dapagliflozin on the incidence of cardiovascular events (DECLARE-TIMI58) . Available from http://clinicaltrials.gov/ct2/show/NCT01730534?term=declare&rank=2. Last accessed 16 March 2015
  • Fujita Y , Inagaki N . Renal sodium glucose cotransporter 2 inhibitors as a novel therapeutic approach to treatment of type 2 diabetes: clinical data and mechanism of action. J Diabetes Investig 2014;5:265–75
  • Liu X , Xiao Q , Zhang L , Yang Q , Liu X , Xu L , Cheng W . The long-term efficacy and safety of DPP-IV inhibitors monotherapy and in combination with metformin in 18 980 patients with type-2 diabetes mellitus-a meta-analysis. Pharmacoepidemiol Drug Saf 2014;23:687–98
  • Leiter LA , Yoon KH , Arias P , Langslet G , Xie J , Balis DA , 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;38:355–64
  • Goke B , Gallwitz B , Eriksson JG , Hellqvist A , Gause-Nilsson I . Saxagliptin vs. glipizide as add-on therapy in patients with type 2 diabetes mellitus inadequately controlled on metformin alone: long-term (52-week) extension of a 52-week randomised controlled trial. Int J Clin Pract 2013;67:307–16
  • Buse JB , Henry RR , Han J , Kim DD , Fineman MS , Baron AD ; Exenatide-113 Clinical Study Group . Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes. Diabetes Care 2004;27:2628–35
  • Roberts VL , Stewart J , Issa M , Lake B , Melis R . Triple therapy with glimepiride in patients with type 2 diabetes mellitus inadequately controlled by metformin and a thiazolidinedione: results of a 30-week, randomized, double-blind, placebo-controlled, parallel-group study. Clin Ther 2005;27:1535–47
  • Pi-Sunyer FX . The impact of weight gain on motivation, compliance, and metabolic control in patients with type 2 diabetes mellitus. Postgrad Med 2009;121:94–107
  • Merovci A , Solis-Herrera C , Daniele G , Eldor R , Fiorentino TV , Tripathy D , et al. Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production. J Clin Invest 2014;124:509–14
  • Ferrannini E , Muscelli E , Frascerra S , Baldi S , Mari A , Heise T , et al. Metabolic response to sodium-glucose cotransporter 2 inhibition in type 2 diabetic patients. J Clin Invest 2014;124:499–508
  • Hansen L , Iqbal N , Ekholm E , Cook W , Hirshberg B . Postprandial dynamics of plasma glucose, insulin, and glucagon in patients with type 2 diabetes treated with saxagliptin plus dapagliflozin add-on to metformin therapy. Endocr Pract 2014;20:1187–97
  • Scirica BM , Bhatt DL , Braunwald E , Steg PG , Davidson J , Hirshberg B , et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med 2013;369:1317–26
  • White WB , Cannon CP , Heller SR , Nissen SE , Bergenstal RM , Bakris GL , et al. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med 2013;369:1327–35
  • Zannad F , Cannon C , Cushman WC , Bakris GL , Menon V , Perez AT , et al. Heart failure and mortality outcomes in patients with type 2 diabetes taking alogliptin versus placebo in EXAMINE: a multicentre, randomised, double-blind trial. Lancet 2015. [Epub ahead of print]
  • Inzucchi SE , Bergenstal RM , Buse JB , Diamant M , Ferrannini E , Nauck M , 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;38:140–9
  • Rosenstock J , Marx N , Kahn SE , Zinman B , Kastelein JJ , Lachin JM , et al. Cardiovascular outcome trials in type 2 diabetes and the sulphonylurea controversy: rationale for the active-comparator CAROLINA trial. Diab Vasc Dis Res 2013;10:289–301
  • Green JB , Bethel MA , Paul SK , Ring A , Kaufman KD , Shapiro DR , et al. Rationale, design, and organization of a randomized, controlled Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) in patients with type 2 diabetes and established cardiovascular disease. Am Heart J 2013;166:983–989 e7
  • Cardiovascular and renal microvascular outcome study with linagliptin in patients with type 2 diabetes mellitus high vascular risk (CARMELINA) . US National Institutes of Health, ClinicalTrials.gov [online]. Available from http://clinicaltrials.gov/ct2/show/NCT01897532?term=NCT01897532&rank=1, Last accessed 16 March 2015
  • Jurczak MJ , Lee HY , Birkenfeld AL , Jornayvaz FR , Frederick DW , Pongratz RL , et al. SGLT2 deletion improves glucose homeostasis and preserves pancreatic beta-cell function. Diabetes 2011;60:890–8

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.