Combination SGLT2 inhibitor and GLP-1 receptor agonist therapy: a complementary approach to the treatment of type 2 diabetes

Postgraduate Medicine

Volumn 129, Issue 7, 2017, Pages 686-697

  Busch, Robert S ^a   Kane, Michael P ^b  

^a ALBANY MEDICAL CENTER   (United States)

^b ALBANY COLLEGE OF PHARMACY AND HEALTH SCIENCES   (United States)

Author keywords

Combination therapy; complementary actions; dual therapy; GLP 1 receptor agonists; SGLT2 inhibitors; type 2 diabetes

Indexed keywords

CANAGLIFLOZIN; DAPAGLIFLOZIN; EMPAGLIFLOZIN; EXENDIN 4; GLUCAGON LIKE PEPTIDE 1 RECEPTOR AGONIST; HEMOGLOBIN A1C; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; INSULIN GLARGINE; LIRAGLUTIDE; LIXISENATIDE; LOW DENSITY LIPOPROTEIN CHOLESTEROL; METFORMIN; SEMAGLUTIDE; SODIUM GLUCOSE COTRANSPORTER 2 INHIBITOR; SULFONYLUREA; ANTIDIABETIC AGENT; GLUCAGON LIKE PEPTIDE 1 RECEPTOR; SODIUM GLUCOSE COTRANSPORTER;

ACUTE CORONARY SYNDROME; BODY WEIGHT; CARDIOVASCULAR RISK; DRUG EFFICACY; DRUG SAFETY; GLUCOSE INTOLERANCE; GLYCEMIC CONTROL; HAZARD RATIO; HEART FAILURE; HYPERLIPIDEMIA; HYPERTENSION; HYPOGLYCEMIA; KIDNEY DISEASE; META ANALYSIS (TOPIC); NON INSULIN DEPENDENT DIABETES MELLITUS; OBESITY; PHARMACODYNAMICS; REVIEW; SYSTOLIC BLOOD PRESSURE; WATER LOSS; ADULT; AGED; AGONISTS; ALTERNATIVE MEDICINE; COMPLICATION; DIABETIC COMPLICATION; FEMALE; HUMAN; MALE; MIDDLE AGED; VERY ELDERLY;

ADULT; AGED; AGED, 80 AND OVER; COMPLEMENTARY THERAPIES; DIABETES COMPLICATIONS; DIABETES MELLITUS, TYPE 2; FEMALE; GLUCAGON-LIKE PEPTIDE-1 RECEPTOR; HUMANS; HYPOGLYCEMIC AGENTS; MALE; MIDDLE AGED; SODIUM-GLUCOSE TRANSPORT PROTEINS;

EID: 85021428641     PISSN: 00325481     EISSN: 19419260     Source Type: Journal    
DOI: 10.1080/00325481.2017.1342509     Document Type: Review

References (90)

1. Defronzo RA., Banting Lecture. From the triumvirate to the ominous octet:a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes. 2009;58:773–795.
2. American Diabetes Association. Standards of medical care in diabetes - 2017. Diabetes Care. 2017;40(Suppl 1):S1–S135.
3. Haffner SM, Lehto S, Rönnemaa T, et al. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med. 1998;339:229–234.
4. Garber AJ, Abrahamson MJ, Barzilay JI, et al. 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;22:84–113.
5. Handelsman Y, Bloomgarden ZT, Grunberger G, et al. American Association of Clinical Endocrinologists and American College of Endocrinology–clinical practice guidelines for developing a diabetes mellitus comprehensive care plan–2015. Endocr Pract. 2015;21(Suppl 1):1–87.
6. Wilding JPH, Rajeev SP, DeFronzo RA. Positioning SGLT2 inhibitors/incretin-based therapies in the treatment algorithm. Diabetes Care. 2016;39(Suppl 2):S154–S164.
7. 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.
8. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373:2117–2128.
9. Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375:311–322.
10. Tahrani AA, Barnett AH, Bailey CJ. Pharmacology and therapeutic implications of current drugs for type 2 diabetes mellitus. Nat Rev Endocrinol. 2016;12:566–592.
11. Baggio LL, Drucker DJ. Biology of incretins:GLP-1 and GIP. Gastroenterology. 2007;132:2131–2157.
12. Nauck MA, Meier JJ. GLP-1 receptor agonists and SGLT2 inhibitors:a couple at last? Lancet Diabetes Endocrinol. 2016;4:963–964.
13. Inzucchi 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;38:140–149.
14. Drucker DJ. Deciphering metabolic messages from the gut drives therapeutic innovation:the 2014 Banting Lecture. Diabetes. 2015;64:317–326.
15. Campbell JE, Drucker DJ. Pharmacology, physiology, and mechanisms of incretin hormone action. Cell Metab. 2013;17:819–837.
16. Ussher JR, Drucker DJ. Cardiovascular actions of incretin-based therapies. Circ Res. 2014;114:1788–1803.
17. Zhao T, Parikh P, Bhashyam S, et al. Direct effects of glucagon-like peptide-1 on myocardial contractility and glucose uptake in normal and postischemic isolated rat hearts. J Pharmacol Exp Ther. 2006;317:1106–1113.
18. Ban K, Noyan-Ashraf MH, Hoefer J, et al. Cardioprotective and vasodilatory actions of glucagon-like peptide 1 receptor are mediated through both glucagon-like peptide 1 receptor-dependent and -independent pathways. Circulation. 2008;117:2340–2350.
19. Avogaro A, Vigili de Kreutzenberg S, Fadini GP. Cardiovascular actions of GLP-1 and incretin-based pharmacotherapy. Curr Diabetes Rep. 2014;14:483.
20. Nikolaidis LA, Elahi D, Hentosz T, et al. Recombinant glucagon-like peptide-1 increases myocardial glucose uptake and improves left ventricular performance in conscious dogs with pacing-induced dilated cardiomyopathy. Circulation. 2004;110:955–961.
21. Timmers L, Henriques JP, de Kleijn DP, et al. Exenatide reduces infarct size and improves cardiac function in a porcine model of ischemia and reperfusion injury. J Am Coll Cardiol. 2009;53:501–510.
22. Sonne DP, Engstrøm T, Treiman M. Protective effects of GLP-1 analogues exendin-4 and GLP-1 (9-36)amide against ischemia-reperfusion injury in rat heart. Regul Pept. 2008;146:243–249.
23. Marso SP, Bain SC, Consoli A, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016;375:1834–1844.
24. Invokana® (canagliflozin) tablets:US prescribing information. Titusville (NJ):Janssen Pharmaceuticals Inc.; 2017.
25. Farxiga® (dapagliflozin) tablets:US prescribing information. Wilmington (DE):AstraZeneca Pharmaceuticals LP; 2017.
26. Jardiance® (empagliflozin) tablets:US prescribing information. Ridgefield (CT):Boehringer Ingelheim; 2016.
27. Ferrannini E, Mark M, Mayoux E. CV protection in the EMPA-REG OUTCOME trial:a “thrifty substrate” hypothesis. Diabetes Care. 2016;39:1108–1114.
28. Inzucchi SE, Zinman B, Wanner C, et al. SGLT-2 inhibitors and cardiovascular risk:proposed pathways and review of ongoing outcome trials. Diabetes Vasc Dis Res. 2015;12:90–100.
29. Merovci A, Solis-Herrera C, Daniele G, et al. Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production. J Clin Invest. 2014;124:509–514.
30. Abdul-Ghani M, Del Prato S, Chilton R, et al. SGLT2 inhibitors and cardiovascular risk:lessons learned from the EMPA-REG OUTCOME study. Diabetes Care. 2016;39:717–725.
31. Plosker GL. Dapagliflozin:a review of its use in patients with type 2 diabetes. Drugs. 2014;74:2191–2209.
32. DeFronzo RA. The EMPA-REG study:what has it told us? A diabetologist’s perspective. J Diabetes Complications. 2016;30:1–2.
33. McMurray J. EMPA-REG - the “diuretic hypothesis”. J Diabetes Complications. 2016;30:3–4.
34. 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.
35. Mearns 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:e0125879.
36. Zaccardi F, Htike ZZ, Webb DR, et al. 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.
37. Zhong X, Zhang T, Liu Y, et al. Effects of three injectable antidiabetic agents on glycaemic control, weight change and drop-out in type 2 diabetes suboptimally controlled with metformin and/or a sulfonylurea:a network meta-analysis. Diabetes Res Clin Pract. 2015;109:451–460.
38. 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.
39. Liu F-P, Dong -J-J, Yang Q, et al. Glucagon-like peptide 1 receptor agonist therapy is more efficacious than insulin glargine for poorly controlled type 2 diabetes:a systematic review and meta-analysis. J Diabetes. 2015;7:322–328.
40. Palmer SC, Mavridis D, Nicolucci A, et al. Comparison of clinical outcomes and adverse events associated with glucose-lowering drugs in patients with type 2 diabetes:a meta-analysis. JAMA. 2016;316:313–324.
41. Potts JE, Gray LJ, Brady EM, et al. The effect of glucagon-like peptide 1 receptor agonists on weight loss in type 2 diabetes:a systematic review and mixed treatment comparison meta-analysis. PLoS One. 2015;10:e0126769.
42. Sun F, Wu S, Wang J, et al. Effect of glucagon-like peptide-1 receptor agonists on lipid profiles among type 2 diabetes:a systematic review and network meta-analysis. Clin Ther. 2015;37:225–241.
43. Sun F, Chai S, Li L, et al. Effects of glucagon-like peptide-1 receptor agonists on weight loss in patients with type 2 diabetes:a systematic review and network meta-analysis. J Diabetes Res. 2015;2015:157201.
44. Liu XY, Zhang N, Chen R, et al. Efficacy and safety of sodium-glucose cotransporter 2 inhibitors in type 2 diabetes:a meta-analysis of randomized controlled trials for 1 to 2years. J Diabetes Complications. 2015;29:1295–1303.
45. Shyangdan DS, Uthman OA, Waugh N. SGLT-2 receptor inhibitors for treating patients with type 2 diabetes mellitus:a systematic review and network meta-analysis. BMJ Open. 2016;6:e009417.
46. Vasilakou D, Karagiannis T, Athanasiadou E, et al. Sodium-glucose cotransporter 2 inhibitors for type 2 diabetes:a systematic review and meta-analysis. Ann Intern Med. 2013;159:262–274.
47. Zaccardi F, Webb DR, Htike ZZ, et al. Efficacy and safety of sodium-glucose co-transporter-2 inhibitors in type 2 diabetes mellitus:systematic review and network meta-analysis. Diabetes Obes Metab. 2016;18:783–794.
48. Neeland IJ, McGuire DK, Chilton R, et al. Empagliflozin reduces body weight and indices of adipose distribution in patients with type 2 diabetes mellitus. Diabetes Vasc Dis Res. 2016;13:119–126.
49. Fadini GP, Bonora BM, Zatti G, et al. Effects of the SGLT2 inhibitor dapagliflozin on HDL cholesterol, particle size, and cholesterol efflux capacity in patients with type 2 diabetes:a randomized placebo-controlled trial. Cardiovasc Diabetol. 2017;16:42.
50. Grimm M, Han J, Weaver C, et al. Efficacy, safety, and tolerability of exenatide once weekly in patients with type 2 diabetes mellitus:an integrated analysis of the DURATION trials. Postgrad Med. 2013;125:47–57.
51. Blonde L, Klein EJ, Han J, et al. Interim analysis of the effects of exenatide treatment on A1C, weight and cardiovascular risk factors over 82 weeks in 314 overweight patients with type 2 diabetes. Diabetes Obes Metab. 2006;8:436–447.
52. Wanner C, Inzucchi SE, Lachin JM, et al. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med. 2016;375:323–334.
53. Scheen AJ. Evaluating SGLT2 inhibitors for type 2 diabetes:pharmacokinetic and toxicological considerations. Expert Opin Drug Metab Toxicol. 2014;10:647–663.
54. Thomas MC. Renal effects of dapagliflozin in patients with type 2 diabetes. Ther Adv Endocrinol Metab. 2014;5:53–61.
55. Pfeffer MA, Claggett B, Diaz R, et al. Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N Engl J Med. 2015;373:2247–2257.
56. Holman RR, Bethel MA, George J, et al. Rationale and design of the EXenatide Study of Cardiovascular Event Lowering (EXSCEL) trial. Am Heart J. 2016;174:103–110.
57. Eli Lilly and Company [Internet]. The effect of dulaglutide on major cardiovascular events in patients with type 2 diabetes:Researching cardiovascular Events with a Weekly Incretin in Diabetes (REWIND). ClinicalTrials.gov record:NCT01394952 [cited 2016 Nov 14]. Available from:https://www.clinicaltrials.gov/ct2/show/NCT01394952
58. GlaxoSmithKline [Internet]. A long term, randomised, double blind, placebo-controlled study to determine the effect of albiglutide, when added to standard blood glucose lowering therapies, on major cardiovascular events in patients with type 2 diabetes mellitus (HARMONY outcomes). ClinicalTrials.gov record:NCT02465515 [cited 2016 Nov 14]. Available from:https://www.clinicaltrials.gov/ct2/show/NCT02465515
59. AstraZeneca [Internet]. Dapagliflozin effect on cardiovascular events a multicenter, randomized, double-blind, placebo-controlled trial to evaluate the effect of dapagliflozin 10 mg once daily on the incidence of cardiovascular death, myocardial infarction or ischemic stroke in patients with type 2 diabetes. ClinicalTrials.gov record:NCT01730534 [cited 2016 Nov 14]. Available from:https://www.clinicaltrials.gov/ct2/show/NCT01730534
60. Janssen Research & Development [Internet]. A randomized, multicenter, double-blind, parallel, placebo-controlled study of the effects of JNJ-28431754 on cardiovascular outcomes in adult subjects with type 2 diabetes mellitus. [cited 2016 Nov 14]. Available from:https://www.clinicaltrials.gov/ct2/show/NCT01032629
61. Ogawa W, Sakaguchi K. Euglycemic diabetic ketoacidosis induced by SGLT2 inhibitors:possible mechanism and contributing factors. J Diabetes Investig. 2016;7:135–138.
62. Handelsman Y, Henry RR, Bloomgarden ZT, et al. American Association of Clinical Endocrinologists and American College of Endocrinology position statement on the association of SGLT-2 inhibitors and diabetic ketoacidosis. Endocr Pract. 2016;22:753–762.
63. Ferrannini G, Hach T, Crowe S, et al. Energy balance after sodium-glucose cotransporter 2 inhibition. Diabetes Care. 2015;38:1730–1735.
64. Hollander P, Bays HE, Rosenstock J, et al. Coadministration of canagliflozin and phentermine for weight management in overweight and obese individuals without diabetes:a randomized clinical trial. Diabetes Care. 2017;40:632–639.
65. Frías JP, Guja C, Hardy E, et al. Exenatide once weekly plus dapagliflozin once daily versus exenatide or dapagliflozin alone in patients with type 2 diabetes inadequately controlled with metformin monotherapy (DURATION-8):a 28 week, multicentre, double-blind, phase 3, randomised controlled trial. Lancet Diabetes Endocrinol. 2016;4:1004–1016.
66. Fulcher G, Matthews DR, Perkovic V, et al. Efficacy and safety of canagliflozin when used in conjunction with incretin-mimetic therapy in patients with type 2 diabetes. Diabetes Obes Metab. 2016;18:82–91.
67. Lundkvist P, Sjöström CD, Amini A, et al. Dapagliflozin once-daily and exenatide once-weekly dual therapy:a 24-week randomized, placebo-controlled, phase II study examining effects on body weight and prediabetes in obese adults without diabetes. Diab Obes Metab. 2017;19:49–60.
68. Lundkvist P, Pereira MJ, Katsogiannos P, et al. Dapagliflozin once daily plus exenatide once weekly in obese adults without diabetes:sustained reductions in bodyweight, glycaemia, and blood pressure over 1 year. Diabetes Obes Metab. 2017 Mar 27. Epub ahead of print. doi:10.1111/dom.12954.
69. Saroka RM, Kane MP, Busch RS, et al. SGLT-2 inhibitor therapy added to GLP-1 agonist therapy in the management of T2DM. Endocr Pract. 2015;21:1315–1322.
70. McGovern AP, Dutta N, Watters K, et al. Additive weight loss effect with a combination of an oral sodium-glucose cotransporter 2 (SGLT2) inhibitor and a glucagon-like peptide 1 (GLP-1) agonist in type 2 diabetes [abstract A6]. Diabet Med. 2015;32:2–3.
71. García-Rubi E. Real life experience with the combination of exenatide LAR and dapagliflozin in obese type 2 diabetic patients in Mexico City [abstract 223]. Abstract presented at:26th American Association of Clinical Endocrinologists (AACE) Annual Scientific & Clinical Congress; 2016 May 3–7; Austin, TX.
72. Kalra S, Gupta Y. Choosing injectable therapy:the metabolic fulcrum. J Pak Med Assoc. 2016;66:908–909.
73. Kalra S, Gupta Y, Kishor K. The cardiovascular phenotype:impact on choice of glucose-lowering therapy. J Pak Med Assoc. 2016;66:480–482.
74. Cho YM. Incretin physiology and pathophysiology from an Asian perspective. J Diabetes Investig. 2015;6:495–507.
75. Yabe D, Seino Y, Fukushima M, et al. Beta cell dysfunction versus insulin resistance in the pathogenesis of type 2 diabetes in East Asians. Curr Diabetes Rep. 2015;15:602.
76. Gauthier B, Singh SR, Virani A, et al. Perspectives and experiences of health care professionals and patients regarding treatments for type 2 diabetes. Can Pharm J (Ott). 2014;147:45–54.
77. Qiao Q, Grandy S, Hiller J, et al. Clinical and patient-related variables associated with initiating GLP-1 receptor agonist therapy in type 2 diabetes patients in primary care in Germany. Plos One. 2016;11:e0152281.
78. 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.
79. Ampudia-Blasco FJ, Benhamou PY, Charpentier G, et al. A decision support tool for appropriate glucose-lowering therapy in patients with type 2 diabetes. Diabetes Technol Ther. 2015;17:194–202.
80. Hauber AB, Nguyen H, Posner J, et al. A discrete-choice experiment to quantify patient preferences for frequency of glucagon-like peptide-1 receptor agonist injections in the treatment of type 2 diabetes. Curr Med Res Opin. 2016;32:251–262.
81. Janssen EM, Segal JB, Bridges JF. A framework for instrument development of a choice experiment:an application to type 2 diabetes. Patient. 2016;9:465–479.
82. Shillington AC, Col N, Bailey RA, et al. Development of a patient decision aid for type 2 diabetes mellitus for patients not achieving glycemic control on metformin alone. Patient Prefer Adherence. 2015;9:609–617.
83. Tziomalos K. Adherence to antihyperglycemic treatment:a work in progress. Exp Opin Pharmacother. 2016;17:1579–1580.
84. Farmer AJ, Rodgers LR, Lonergan M, et al. Adherence to oral glucose-lowering therapies and associations with 1-year HbA1c:a retrospective cohort analysis in a large primary care database. Diabetes Care. 2016;39:258–263.
85. Cai J, Wang Y, Baser O, et al. Comparative persistence and adherence with newer anti-hyperglycemic agents to treat patients with type 2 diabetes in the United States. J Med Econ. 2016;19:1–12.
86. Saundankar V, Peng X, Fu H, et al. Predictors of change in adherence status from 1 year to the next among patients with type 2 diabetes mellitus on oral antidiabetes drugs. J Manag Care Spec Pharm. 2016;22:467–482.
87. Yavuz DG, Bilen H, Sancak S, et al. Impact of telephonic interviews on persistence and daily adherence to insulin treatment in insulin-naive type 2 diabetes patients:dropout study. Patient Prefer Adherence. 2016;10:851–861.
88. Qiao Q, Ouwens MJ, Grandy S, et al. Adherence to GLP-1 receptor agonist therapy administered by once-daily or once-weekly injection in patients with type 2 diabetes in Germany. Diabetes Metab Syndr Obes. 2016;9:201–205.
89. Lopez JM, Annunziata K, Bailey RA, et al. Impact of hypoglycemia on patients with type 2 diabetes mellitus and their quality of life, work productivity, and medication adherence. Patient Prefer Adherence. 2014;8:683–692.
90. Spain CV, Wright JJ, Hahn RM, et al. Self-reported barriers to adherence and persistence to treatment with injectable medications for type 2 diabetes. Clin Ther. 2016;38:1653–1664.