Similar efficacy and safety of once-weekly dulaglutide in patients with type 2 diabetes aged ≥65 and M A Boustani  1 , I Pittman 4th  2 , M Yu  3 , V T Thieu  4 , O J Varnado  4 , R Juneja  4 Affiliations Expand Affiliations 1 Indiana University, Indianapolis, IN, USA. 2 Providence Medical Group, Terre Haute, IN, USA. 3 Eli Lilly and Company, Toronto, ON, Canada. 4 Eli Lilly and Company, Indianapolis, IN, USA. PMID: 27161178 PMCID: PMC5089646 DOI: 10.1111/dom.12687 Free PMC article Item in Clipboard

M A Boustani, I Pittman 4th, M Yu, V T Thieu, O J Varnado, R Juneja, M A Boustani, I Pittman 4th, M Yu, V T Thieu, O J Varnado, R Juneja

Abstract

Aims: To evaluate the efficacy and safety of dulaglutide 1.5 and 0.75 mg in elderly patients (aged ≥65 years) with type 2 diabetes (T2D) in six phase III clinical trials.

Methods: Patients were grouped into two age groups: ≥65 and <65 years. Pooled analysis for glycated haemoglobin (HbA1c) change from baseline, percentage of patients achieving HbA1c targets, and gastrointestinal tolerability were evaluated at 26 weeks for each dulaglutide dose. Change in weight from baseline and rates of hypoglycaemia were evaluated for each individual study.

Results: A total of 958 of 5171 (18.5%) patients were aged ≥65 years. The reductions in HbA1c were similar between age groups for dulaglutide 1.5 mg-treated patients {least squares [LS] mean for patients aged ≥65 years: -1.24 [95% confidence interval (CI) -1.36, -1.12] and for patients aged <65 years: -1.29 [95% CI -1.38, -1.20]} and for dulaglutide 0.75 mg-treated patients [LS mean for patients aged ≥65 years: -1.16 (95% CI -1.29, -1.03) and for patients aged <65 years: -1.10 (95% CI -1.19, -1.01)] at 26 weeks. The percentages of patients who achieved HbA1c targets of <7, <8 or <9% were also similar in the two groups with both dulaglutide doses. Patients aged ≥65 years had similar weight change to patients aged <65 years. Severe hypoglycaemic events were infrequent. A similar incidence of gastrointestinal adverse events was observed in each age group with both dulaglutide doses.

Conclusion: Both dulaglutide doses were well tolerated, with similar efficacy in patients with T2D aged ≥65 years to those aged <65 years. Dulaglutide can be considered a safe and effective treatment option for use in older adults.

Trial registration: ClinicalTrials.gov NCT01064687 NCT01075282 NCT01126580 NCT01191268 NCT00734474 NCT01624259.

Keywords: dulaglutide; type 2 diabetes.

© 2016 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
Pooled analysis of glycated haemoglobin (HbA1c) change from baseline to 26 weeks. HbA1c change from baseline to 26 weeks for pooled analysis from AWARD‐1 through AWARD‐6 for dulaglutide 1.5 mg and AWARD‐1 through AWARD‐5 for dulaglutide 0.75 mg. Data presented as least squares means and standard errors. DU, dulaglutide.
Figure 2
Figure 2
Glycated haemoglobin (HbA1c) change from baseline to 26 weeks by individual study. Data presented as LS means and 95% CIs. AWARD, Assessment of Weekly AdministRation of LY2189265 (dulaglutide) in Diabetes; BL, baseline; HbAlc, glycated haemoglobin; MET, metformin; SU, sulphonylurea; TZD, thiazolidinedione; yrs, years.
Figure 3
Figure 3
Change in weight from baseline to 26 weeks by individual study. Data presented as least squares means and 95% confidence intervals. AWARD, Assessment of Weekly AdministRation of LY2189265 (dulaglutide) in Diabetes; BL, baseline; MET, metformin; SU, sulphonylurea; TZD, thiazolidinedione.

References

    1. Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 2004; 27: 1047–1053.
    1. Inzucchi SE, Bergenstal RM, Buse JB et al. Management of hyperglycemia in type 2 diabetes: a patient‐centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2012; 35: 1364–1379.
    1. 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.
    1. Gregg EW, Yaffe K, Cauley JA et al. Is diabetes associated with cognitive impairment and cognitive decline among older women? Study of Osteoporotic Fractures Research Group. Arch Intern Med 2000; 160: 174–180.
    1. Gregg EW, Mangione CM, Cauley JA et al. Diabetes and incidence of functional disability in older women. Diabetes Care 2002; 25: 61–67.
    1. Gregg EW, Sorlie P, Paulose‐Ram R et al. Prevalence of lower‐extremity disease in the US adult population > =40 years of age with and without diabetes: 1999‐2000 national health and nutrition examination survey. Diabetes Care 2004; 27: 1591–1597.
    1. Kirkman MS, Briscoe VJ, Clark N et al. Diabetes in older adults: a consensus report. J Am Geriatr Soc 2012; 60: 2342–2356.
    1. Menz HB, Lord SR, St George R, Fitzpatrick RC. Walking stability and sensorimotor function in older people with diabetic peripheral neuropathy. Arch Phys Med Rehabil 2004; 85: 245–252.
    1. Richardson JK, Thies S, Ashton‐Miller JA. An exploration of step time variability on smooth and irregular surfaces in older persons with neuropathy. Clin Biomech (Bristol, Avon) 2008; 23: 349–356.
    1. Richardson JK, Thies SB, DeMott TK, Ashton‐Miller JA. Gait analysis in a challenging environment differentiates between fallers and nonfallers among older patients with peripheral neuropathy. Arch Phys Med Rehabil 2005; 86: 1539–1544.
    1. Halter JB, Morrow LA. Use of sulfonylurea drugs in elderly patients. Diabetes Care 1990; 13: 86–92.
    1. American Diabetes Association. Standards of medical care in diabetes–2012. Diabetes Care 2012; 35(Suppl. 1): S11–63.
    1. Sinclair AJ, Paolisso G, Castro M, Bourdel‐Marchasson I, Gadsby R, Rodriguez ML. European Diabetes Working Party for Older People 2011 clinical guidelines for type 2 diabetes mellitus. Executive summary. Diabetes Metab 2011; 37 Suppl. 3: S27–S38.
    1. Bryan J, Crane A, Vila‐Carriles WH, Babenko AP, Aguilar‐Bryan L. Insulin secretagogues, sulfonylurea receptors and K(ATP) channels. Curr Pharm Des 2005; 11: 2699–2716.
    1. Kahn SE, Haffner SM, Heise MA et al. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med 2006; 355: 2427–2443.
    1. Ober SK, Watts S, Lawrence RH. Insulin use in elderly diabetic patients. Clin Interv Aging 2006; 1: 107–113.
    1. Bode B. Liraglutide: a review of the first once‐daily GLP‐1 receptor agonist. Am J Manag Care 2011; 17: S59–S70.
    1. Pencek R, Blickensderfer A, Li Y, Brunell SC, Chen S. Exenatide once weekly for the treatment of type 2 diabetes: effectiveness and tolerability in patient subpopulations. Int J Clin Pract 2012; 66: 1021–1032.
    1. Raccah D, Miossec P, Esposito V, Niemoeller E, Cho M, Gerich J. Efficacy and safety of lixisenatide in elderly (>/=65 years old) and very elderly (>/=75 years old) patients with type 2 diabetes: an analysis from the GetGoal phase III programme. Diabetes Metab Res Rev 2015; 31: 204–211.
    1. Russo E, Penno G, Del Prato S. Managing diabetic patients with moderate or severe renal impairment using DPP‐4 inhibitors: focus on vildagliptin. Diabetes Metab Syndr Obes 2013; 6: 161–170.
    1. Barrington P, Chien JY, Showalter HD et al. A 5‐week study of the pharmacokinetics and pharmacodynamics of LY2189265, a novel, long‐acting glucagon‐like peptide‐1 analogue, in patients with type 2 diabetes. Diabetes Obes Metab 2011; 13: 426–433.
    1. Barrington P, Chien JY, Tibaldi F, Showalter HD, Schneck K, Ellis B. LY2189265, a long‐acting glucagon‐like peptide‐1 analogue, showed a dose‐dependent effect on insulin secretion in healthy subjects. Diabetes Obes Metab 2011; 13: 434–438.
    1. Matfin G, Van Brunt K, Zimmermann AG, Threlkeld R, Ignaut DA. Safe and effective use of the once weekly dulaglutide single‐dose pen in injection‐naive patients with type 2 diabetes. J Diabetes Sci Technol 2015; 9: 1071–1079.
    1. Trulicity [Summary of Product Characteristics]. Houten, The Netherlands: Eli Lilly and Company; 2014.
    1. Umpierrez G, Tofe Povedano S, Perez Manghi F, Shurzinske L, Pechtner V. Efficacy and safety of dulaglutide monotherapy versus metformin in type 2 diabetes in a randomized controlled trial (AWARD‐3). Diabetes Care 2014; 37: 2168–2176.
    1. Nauck M, Weinstock RS, Umpierrez GE, Guerci B, Skrivanek Z, Milicevic Z. Efficacy and safety of dulaglutide versus sitagliptin after 52 weeks in type 2 diabetes in a randomized controlled trial (AWARD‐5). Diabetes Care 2014; 37: 2149–2158.
    1. Blonde L, Jendle J, Gross J et al. Once‐weekly dulaglutide versus bedtime insulin glargine, both in combination with prandial insulin lispro, in patients with type 2 diabetes (AWARD‐4): a randomised, open‐label, phase 3, non‐inferiority study. Lancet 2015; 385: 2057–2066.
    1. Giorgino F, Benroubi M, Sun JH, Zimmermann AG, Pechtner V. Efficacy and safety of once‐weekly dulaglutide versus insulin glargine in patients with type 2 diabetes on metformin and glimepiride (AWARD‐2). Diabetes Care 2015; 38: 2241–2249.
    1. Wysham C, Blevins T, Arakaki R et al. Efficacy and safety of dulaglutide added onto pioglitazone and metformin versus exenatide in type 2 diabetes in a randomized controlled trial (AWARD‐1). Diabetes Care 2014; 37: 2159–2167.
    1. Dungan KM, Povedano ST, Forst T et al. Once‐weekly dulaglutide versus once‐daily liraglutide in metformin‐treated patients with type 2 diabetes (AWARD‐6): a randomised, open‐label, phase 3, non‐inferiority trial. Lancet 2014; 384: 1349–1357.
    1. Fonseca V, McDuffie R, Calles J et al. Determinants of weight gain in the action to control cardiovascular risk in diabetes trial. Diabetes Care 2013; 36: 2162–2168.
    1. Brodows RG. Benefits and risks with glyburide and glipizide in elderly NIDDM patients. Diabetes Care 1992; 15: 75–80.
    1. Bode BW, Brett J, Falahati A, Pratley RE. Comparison of the efficacy and tolerability profile of liraglutide, a once‐daily human GLP‐1 analog, in patients with type 2 diabetes >/=65 and <65 years of age: a pooled analysis from phase III studies. Am J Geriatr Pharmacother 2011; 9: 423–433.
    1. Barbagallo M, Dominguez LJ. Type 2 diabetes mellitus and Alzheimer's disease. World J Diabetes 2014; 5: 889–893.
    1. Crane PK, Walker R, Larson EB. Glucose levels and risk of dementia. N Engl J Med 2013; 369: 1863–1864.
    1. Dominguez LJ, Paolisso G, Barbagallo M. Glucose control in the older patient: from intensive, to effective and safe. Aging Clin Exp Res 2010; 22: 274–280.

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa