Dapagliflozin once daily plus exenatide once weekly in obese adults without diabetes: Sustained reductions in body weight, glycaemia and blood pressure over 1 year

Diabetes, Obesity and Metabolism

Volumn 19, Issue 9, 2017, Pages 1276-1288

  Lundkvist, Per ^a   Pereira, Maria J ^a   Katsogiannos, Petros ^a   Sjöström, C David ^b   Johnsson, Eva ^b   Eriksson, Jan W ^a  

^a UPPSALA UNIVERSITY   (Sweden)

^b ASTRAZENECA R AND D   (Sweden)

Author keywords

dapagliflozin; exenatide; obesity; prediabetes

Indexed keywords

DAPAGLIFLOZIN; EXENDIN 4; GLUCOSE; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; PLACEBO; 2-(3-(4-ETHOXYBENZYL)-4-CHLOROPHENYL)-6-HYDROXYMETHYLTETRAHYDRO-2H-PYRAN-3,4,5-TRIOL; AGENTS AFFECTING WATER, MOLECULE OR ION TRANSPORT; ANTIDIABETIC AGENT; ANTIOBESITY AGENT; BENZHYDRYL DERIVATIVE; GHRELIN; GHRL PROTEIN, HUMAN; GLUCOSIDE; PEPTIDE; SODIUM GLUCOSE COTRANSPORTER; VENOM;

ABDOMINAL PAIN; ADULT; AGED; ANGIONEUROTIC EDEMA; ARTICLE; BODY COMPOSITION; BODY MASS; CHOLESTEROL BLOOD LEVEL; CLINICAL ARTICLE; CLINICAL EFFECTIVENESS; COLON ADENOCARCINOMA; CONTROLLED STUDY; DECREASED APPETITE; DIZZINESS; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; EYE ALLERGY; FATIGUE; FEMALE; GASTROINTESTINAL HEMORRHAGE; GENITAL TRACT INFECTION; GLUCOSE BLOOD LEVEL; GLYCEMIC CONTROL; HUMAN; INCREASED APPETITE; INJECTION SITE CYST; INJECTION SITE ERYTHEMA; INJECTION SITE MASS; INJECTION SITE NODULE; INJECTION SITE PAIN; INJECTION SITE PRURITUS; INJECTION SITE RASH; INJECTION SITE REACTION; INJECTION SITE SWELLING; MALAISE; MALE; NAUSEA; NUCLEAR MAGNETIC RESONANCE IMAGING; OBESITY; PHASE 2 CLINICAL TRIAL; PRURITUS; RANDOMIZED CONTROLLED TRIAL; SKIN ULCER; SYSTOLIC BLOOD PRESSURE; TREATMENT DURATION; TREATMENT OUTCOME; URINARY TRACT INFECTION; VASCULITIS; WAIST CIRCUMFERENCE; WEIGHT CHANGE; WEIGHT REDUCTION; AGONISTS; ANTAGONISTS AND INHIBITORS; BODY WEIGHT LOSS; CARDIOVASCULAR DISEASE; COMBINATION DRUG THERAPY; DRUG ADMINISTRATION; DRUG EFFECTS; FOLLOW UP; IMPAIRED GLUCOSE TOLERANCE; METABOLISM; MIDDLE AGED; PATHOPHYSIOLOGY; PROOF OF CONCEPT; RISK FACTOR; SWEDEN;

ADIPOSITY; ANTI-OBESITY AGENTS; BENZHYDRYL COMPOUNDS; BODY MASS INDEX; CARDIOVASCULAR DISEASES; DOUBLE-BLIND METHOD; DRUG ADMINISTRATION SCHEDULE; DRUG THERAPY, COMBINATION; FEMALE; FOLLOW-UP STUDIES; GHRELIN; GLUCOSIDES; HUMANS; HYPOGLYCEMIC AGENTS; MALE; MEMBRANE TRANSPORT MODULATORS; MIDDLE AGED; OBESITY; PEPTIDES; PREDIABETIC STATE; PROOF OF CONCEPT STUDY; RISK FACTORS; SODIUM-GLUCOSE TRANSPORT PROTEINS; SWEDEN; VENOMS; WEIGHT LOSS;

EID: 85020067582     PISSN: 14628902     EISSN: 14631326     Source Type: Journal    
DOI: 10.1111/dom.12954     Document Type: Article

References (58)

1. World Health Organization. Obesity and overweight: fact sheet no. 311. 2016. http://www.who.int/mediacentre/factsheets/fs311/en/. Accessed February 2, 2016.
2. International Diabetes Federation. IDF Diabetes Altas. 7th ed; 2015. http://www.diabetesatlas.org/. Accessed February 15, 2016.
3. Diabetes Prevention Program Research Group. Long-term effects of lifestyle intervention or metformin on diabetes development and microvascular complications over 15-year follow-up: the Diabetes Prevention Program Outcomes Study. Lancet Diabetes Endocrinol. 2015;3:866-875.
4. Johns DJ, Hartmann-Boyce J, Jebb SA, Aveyard P. Diet or exercise interventions vs combined behavioral weight management programs: a systematic review and meta-analysis of direct comparisons. J Acad Nutr Diet. 2014;114:1557-1568.
5. Hartmann-Boyce J, Johns DJ, Jebb SA, Summerbell C, Aveyard P. Behavioural weight management programmes for adults assessed by trials conducted in everyday contexts: systematic review and meta-analysis. Obes Rev. 2014;15:920-932.
6. Dhurandhar EJ, Kaiser KA, Dawson JA, Alcorn AS, Keating KD, Allison DB. Predicting adult weight change in the real world: a systematic review and meta-analysis accounting for compensatory changes in energy intake or expenditure. Int J Obes. 2015;39:1181-1187.
7. Krentz AJ, Fujioka K, Hompesch M. Evolution of pharmacological obesity treatments: focus on adverse side-effect profiles. Diabetes Obes Metab. 2016;18:558-570.
8. Halpern B, Oliveira ES, Faria AM, et al. Combinations of drugs in the treatment of obesity. Pharmaceuticals. 2010;3:2398-2415.
9. Bays HE, Weinstein R, Law G, Canovatchel W. Canagliflozin: effects in overweight and obese subjects without diabetes mellitus. Obesity. 2014;22:1042-1049.
10. Zhang F, Tong Y, Su N, et al. Weight loss effect of glucagon-like peptide-1 mimetics on obese/overweight adults without diabetes: a systematic review and meta-analysis of randomized controlled trials. J Diabetes. 2015;7:329-339.
11. Lambers Heerspink HJ, de Zeeuw D, Wie L, Leslie B, List J. Dapagliflozin a glucose-regulating drug with diuretic properties in subjects with type 2 diabetes. Diabetes Obes Metab. 2013;15:853-862.
12. Ferrannini G, Hach T, Crowe S, Sanghvi A, Hall KD, Ferrannini E. Energy balance after sodium-glucose cotransporter 2 inhibition. Diabetes Care. 2015;38:1730-1735.
13. van Bloemendaal L, Ten Kulve JS, la Fleur SE, Ijzerman RG, Diamant M. Effects of glucagon-like peptide 1 on appetite and body weight: focus on the CNS. J Endocrinol. 2014;221:T1-T16.
14. Bailey CJ, Morales Villegas EC, Woo V, Tang W, Ptaszynska A, List JF. Efficacy and safety of dapagliflozin monotherapy in people with type 2 diabetes: a randomized double-blind placebo-controlled 102-week trial. Diabet Med. 2015;32:531-541.
15. Bolinder J, Ljunggren O, Johansson L, et al. Dapagliflozin maintains glycaemic control while reducing weight and body fat mass over 2 years in patients with type 2 diabetes mellitus inadequately controlled on metformin. Diabetes Obes Metab. 2014;16:159-169.
16. Wilding JP, Woo V, Rohwedder K, Sugg J, Parikh S. Dapagliflozin in patients with type 2 diabetes receiving high doses of insulin: efficacy and safety over 2 years. Diabetes Obes Metab. 2014;16:124-136.
17. Diamant M, Van Gaal L, Guerci B, et al. Exenatide once weekly versus insulin glargine for type 2 diabetes (DURATION-3): 3-year results of an open-label randomised trial. Lancet Diabetes Endocrinol. 2014;2:464-473.
18. Henry RR, Klein EJ, Han J, Iqbal N. Efficacy and tolerability of exenatide once weekly over 6 years in patients with type 2 diabetes: an uncontrolled open-label extension of the DURATION-1 study. Diabetes Technol Ther. 2016;18:677-686.
19. Wysham CH, MacConell LA, Maggs DG, Zhou M, Griffin PS, Trautmann ME. Five-year efficacy and safety data of exenatide once weekly: long-term results from the DURATION-1 randomized clinical trial. Mayo Clin Proc. 2015;90:356-365.
20. Lundkvist P, Sjöström CD, Amini S, Pereira MJ, Johnsson E, Eriksson JW. 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. Diabetes Obes Metab. 2017;19:49-60.
21. Liu-Seifert H, Andersen SW, Lipkovich I, Holdridge KC, Siemers E. A novel approach to delayed-start analyses for demonstrating disease-modifying effects in Alzheimer's disease. PLoS ONE. 2015;10:e0119632.
22. Leibel RL, Rosenbaum M, Hirsch J. Changes in energy expenditure resulting from altered body weight. N Engl J Med. 1995;332:621-628.
23. Boswell RG, Kober H. Food cue reactivity and craving predict eating and weight gain: a meta-analytic review. Obes Rev. 2016;17:159-177.
24. Apovian CM, Aronne LJ, Bessesen DH, et al. Pharmacological management of obesity: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2015;100:342-362.
25. Khera R, Murad MH, Chandar AK, et al. Association of pharmacological treatments for obesity with weight loss and adverse events: a systematic review and meta-analysis. JAMA. 2016;315:2424-2434.
26. Kasichayanula S, Liu X, Lacreta F, Griffen SC, Boulton DW. Clinical pharmacokinetics and pharmacodynamics of dapagliflozin, a selective inhibitor of sodium-glucose co-transporter type 2. Clin Pharmacokinet. 2014;53:17-27.
27. Astrup A, Rossner S, Van Gaal L, et al. Effects of liraglutide in the treatment of obesity: a randomised, double-blind, placebo-controlled study. Lancet. 2009;374:1606-1616.
28. Astrup A, Carraro R, Finer N, et al. Safety, tolerability and sustained weight loss over 2 years with the once-daily human GLP-1 analog, liraglutide. Int J Obes. 2012;36:843-854.
29. Pi-Sunyer X, Astrup A, Fujioka K, et al. A randomized, controlled trial of 3.0 mg of liraglutide in weight management. N Engl J Med. 2015;373:11-22.
30. Torgerson JS, Hauptman J, Boldrin MN, Sjöström L. XENical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Diabetes Care. 2004;27:155-161.
31. Krempf M, Louvet JP, Allanic H, Miloradovich T, Joubert JM, Attali JR. Weight reduction and long-term maintenance after 18 months treatment with orlistat for obesity. Int J Obes Relat Metab Disord. 2003;27:591-597.
32. Broom I, Wilding J, Stott P, Myers N. Randomised trial of the effect of orlistat on body weight and cardiovascular disease risk profile in obese patients: UK Multimorbidity Study. Int J Clin Pract. 2002;56:494-499.
33. Rossner S, Sjöström L, Noack R, Meinders AE, Noseda G. Weight loss, weight maintenance, and improved cardiovascular risk factors after 2 years treatment with orlistat for obesity. European Orlistat Obesity Study Group. Obes Res. 2000;8:49-61.
34. Hauptman J, Lucas C, Boldrin MN, Collins H, Segal KR. Orlistat in the long-term treatment of obesity in primary care settings. Arch Fam Med. 2000;9:160-167.
35. Davidson MH, Hauptman J, DiGirolamo M, et al. Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat: a randomized controlled trial. JAMA. 1999;281:235-242.
36. Sjöström L, Rissanen A, Andersen T, et al. Randomised placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients. European Multicentre Orlistat Study Group. Lancet. 1998;352:167-172.
37. Fidler MC, Sanchez M, Raether B, et al. A one-year randomized trial of lorcaserin for weight loss in obese and overweight adults: the BLOSSOM trial. J Clin Endocrinol Metab. 2011;96:3067-3077.
38. Smith SR, Weissman NJ, Anderson CM, et al. Multicenter, placebo-controlled trial of lorcaserin for weight management. N Engl J Med. 2010;363:245-256.
39. Apovian CM, Aronne L, Rubino D, et al. A randomized, phase 3 trial of naltrexone SR/bupropion SR on weight and obesity-related risk factors (COR-II). Obesity. 2013;21:935-943.
40. Wadden TA, Foreyt JP, Foster GD, et al. Weight loss with naltrexone SR/bupropion SR combination therapy as an adjunct to behavior modification: the COR-BMOD trial. Obesity. 2011;19:110-120.
41. Greenway FL, Fujioka K, Plodkowski RA, et al. Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2010;376:595-605.
42. Allison DB, Gadde KM, Garvey WT, et al. Controlled-release phentermine/topiramate in severely obese adults: a randomized controlled trial (EQUIP). Obesity. 2012;20:330-342.
43. 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.
44. Wu JH, Foote C, Blomster J, et al. Effects of sodium-glucose cotransporter-2 inhibitors on cardiovascular events, death, and major safety outcomes in adults with type 2 diabetes: a systematic review and meta-analysis. Lancet Diabetes Endocrinol. 2016;4:411-419.
45. 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.
46. 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.
47. Sonesson C, Johansson PA, Johnsson E, Gause-Nilsson I. Cardiovascular effects of dapagliflozin in patients with type 2 diabetes and different risk categories: a meta-analysis. Cardiovasc Diabetol. 2016;15:37.
48. Monami M, Dicembrini I, Nardini C, Fiordelli I, Mannucci E. Effects of glucagon-like peptide-1 receptor agonists on cardiovascular risk: a meta-analysis of randomized clinical trials. Diabetes Obes Metab. 2014;16:38-47.
49. 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.
50. Rajasekeran H, Lytvyn Y, Cherney DZ. Sodium-glucose cotransporter 2 inhibition and cardiovascular risk reduction in patients with type 2 diabetes: the emerging role of natriuresis. Kidney Int. 2016;89:524-526.
51. Mudaliar S, Alloju S, Henry RR. Can a shift in fuel energetics explain the beneficial cardiorenal outcomes in the EMPA-REG OUTCOME Study? A unifying hypothesis. Diabetes Care. 2016;39:1115-1122.
52. Gilbert RE. SGLT2 inhibitors: beta blockers for the kidney? Lancet Diabetes Endocrinol. 2016;4:814.
53. Irace C, De Luca S, Shehaj E, et al. Exenatide improves endothelial function assessed by flow mediated dilation technique in subjects with type 2 diabetes: results from an observational research. Diab Vasc Dis Res. 2013;10:72-77.
54. Mendis B, Simpson E, MacDonald I, Mansell P. Investigation of the haemodynamic effects of exenatide in healthy male subjects. Br J Clin Pharmacol. 2012;74:437-444.
55. 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.
56. Del Prato S, Nauck M, Durán-Garcia S, et al. Long-term glycaemic response and tolerability of dapagliflozin versus a sulphonylurea as add-on therapy to metformin in patients with type 2 diabetes: 4-year data. Diabetes Obes Metab. 2015;17:581-590.
57. Ptaszynska A, Johnsson KM, Parikh SJ, de Bruin TW, Apanovitch AM, List JF. Safety profile of dapagliflozin for type 2 diabetes: pooled analysis of clinical studies for overall safety and rare events. Drug Saf. 2014;37:815-829.
58. Horowitz M, Aroda VR, Han J, Hardy E, Rayner C. Upper and/or lower GI adverse events with long- vs short-acting GLP-1 receptor agonists: incidence, co-incidence, effects on HbA1c and weight [abstract 15]. Diabetologia. 2015;58 (suppl):S7.