Safety and efficacy of the dipeptidyl peptidase-4 inhibitor linagliptin in elderly patients with type 2 diabetes: A comprehensive analysis of data from 1331 individuals aged≥65years

Diabetes, Obesity and Metabolism

Volumn 16, Issue 11, 2014, Pages 1078-1086

  Schernthaner, G ^a   Barnett, A H ^b   Patel, S ^c   Hehnke, U ^d   von Eynatten, M ^e   Woerle, H J ^d  

^a KRANKENANSTALT RUDOLFSTIFTUNG   (Austria)

^b UNIVERSITY HOSPITALS BIRMINGHAM NHS FOUNDATION TRUST   (United Kingdom)

^c BOEHRINGER INGELHEIM LTD   (United Kingdom)

^d BOEHRINGER INGELHEIM PHARMA GMBH AND CO KG   (Germany)

^e BOEHRINGER INGELHEIM PHARMACEUTICALS INC   (United States)

Author keywords

Diabetes mellitus; DPP IV inhibitor

Indexed keywords

ALANINE AMINOTRANSFERASE; ASPARTATE AMINOTRANSFERASE; HEMOGLOBIN A1C; LINAGLIPTIN; PLACEBO; DIPEPTIDYL PEPTIDASE IV INHIBITOR; GLUCOSE BLOOD LEVEL; GLYCOSYLATED HEMOGLOBIN; HEMOGLOBIN A1C PROTEIN, HUMAN; PURINE DERIVATIVE; QUINAZOLINE DERIVATIVE;

ABNORMAL URINE COMPOSITION; ACUTE KIDNEY FAILURE; AGED; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ARTICLE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; BLADDER DISEASE; BLADDER SPASM; CARDIOVASCULAR MORTALITY; CEREBROVASCULAR ACCIDENT; CHROMATURIA; CHRONIC KIDNEY FAILURE; CONGENITAL MALFORMATION; CONTROLLED STUDY; CYSTITIS; CYSTITIS GLANDULARIS; CYSTITIS NON INFECTIVE; DIABETIC NEPHROPATHY; DRUG EFFICACY; DRUG FATALITY; DRUG HYPERSENSITIVITY; DRUG SAFETY; DYSURIA; ENURESIS; FEMALE; GERIATRIC PATIENT; HEART INFARCTION; HEMATURIA; HEMOGLOBIN BLOOD LEVEL; HUMAN; HYDRONEPHROSIS; HYPOGLYCEMIA; KETONURIA; KIDNEY COLIC; KIDNEY DISEASE; KIDNEY FAILURE; KIDNEY PAIN; KIDNEY TUMOR; LEUKOCYTURIA; MAJOR CLINICAL STUDY; MALE; MICROALBUMINURIA; NEPHROLITHIASIS; NOCTURIA; NON INSULIN DEPENDENT DIABETES MELLITUS; PANCREATITIS; PHASE 3 CLINICAL TRIAL (TOPIC); POLLAKISURIA; PROTEINURIA; PYURIA; RANDOMIZED CONTROLLED TRIAL (TOPIC); SIDE EFFECT; TREATMENT OUTCOME; UNSTABLE ANGINA PECTORIS; URETER STONE; URINARY BLADDER POLYP; URINARY URGENCY; URINE INCONTINENCE; URINE RETENTION; CHEMICALLY INDUCED; CLINICAL TRIAL; COMORBIDITY; DIABETES MELLITUS, TYPE 2; DOUBLE BLIND PROCEDURE; DRUG EFFECTS; GLUCOSE BLOOD LEVEL; INCIDENCE; PHASE 3 CLINICAL TRIAL; RANDOMIZED CONTROLLED TRIAL; VERY ELDERLY;

AGED; AGED, 80 AND OVER; BLOOD GLUCOSE; COMORBIDITY; DIABETES MELLITUS, TYPE 2; DIPEPTIDYL-PEPTIDASE IV INHIBITORS; DOUBLE-BLIND METHOD; FEMALE; HEMOGLOBIN A, GLYCOSYLATED; HUMANS; HYPOGLYCEMIA; INCIDENCE; MALE; PURINES; QUINAZOLINES; TREATMENT OUTCOME;

EID: 84922090477     PISSN: 14628902     EISSN: 14631326     Source Type: Journal    
DOI: 10.1111/dom.12321     Document Type: Article

References (39)

1. Centers for Disease Control and Prevention. National diabetes fact sheet: national estimates and general information on diabetes and prediabetes in the United States, 2011. Atlanta, Georgia: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, 2011. Available from URL: http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2011.pdf. Accessed 15 November 2013.
2. 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.
3. Munshi MN, Segal AR, Suhl E et al. Assessment of barriers to improve diabetes management in older adults: a randomized controlled study. Diabetes Care 2013; 36: 543-549.
4. Zhao Y, Campbell CR, Fonseca V, Shi L. Impact of hypoglycemia associated with antihyperglycemic medications on vascular risks in veterans with type 2 diabetes. Diabetes Care 2012; 35: 1126-1132.
5. McCoy RG, Van Houten HK, Ziegenfuss JY, Shah ND, Wermers RA, Smith SA. Increased mortality of patients with diabetes reporting severe hypoglycemia. Diabetes Care 2012; 35: 1897-1901.
6. Zoungas S, Patel A, Chalmers J et al. Severe hypoglycemia and risks of vascular events and death. N Engl J Med 2010; 363: 1410-1418.
7. Hsu PF, Sung SH, Cheng HM et al. Association of clinical symptomatic hypoglycemia with cardiovascular events and total mortality in type 2 diabetes: a nationwide population-based study. Diabetes Care 2013; 36: 894-900.
8. Stahn A, Pistrosch F, Ganz X et al. Relationship between hypoglycemic episodes and ventricular arrhythmias in patients with type 2 diabetes and cardiovascular diseases: silent hypoglycemias and silent arrhythmias. Diabetes Care 2014; 37: 516-520.
9. Tsujimoto T, Yamamoto-Honda R, Kajio H et al. Vital signs, QT prolongation, and newly diagnosed cardiovascular disease during severe hypoglycemia in type 1 and type 2 diabetic patients. Diabetes Care 2014; 37: 217-225.
10. Frier BM, Schernthaner G, Heller SR. Hypoglycemia and cardiovascular risks. Diabetes Care 2011; 34(Suppl 2): S132-137.
11. Yaffe K, Falvey CM, Hamilton N et al. Association between hypoglycemia and dementia in a biracial cohort of older adults with diabetes mellitus. JAMA 2013; 173: 1300-1306.
12. Ahren B. Avoiding hypoglycemia: a key to success for glucose-lowering therapy in type 2 diabetes. Vasc Health Risk Manage 2013; 9: 155-163.
13. Sinclair A, Morley JE, Rodriguez-Manas L et al. Diabetes mellitus in older people: position statement on behalf of the International Association of Gerontology and Geriatrics (IAGG), the European Diabetes Working Party for Older People (EDWPOP), and the International Task Force of Experts in Diabetes. J Am Med Dir Assoc 2012; 13: 497-502.
14. Inzucchi SE, Bergenstal RM, Buse JB et al. Management of hyperglycaemia 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). Diabetologia 2012; 55: 1577-1596.
15. Greco D, Pisciotta M, Gambina F, Maggio F. Severe hypoglycaemia leading to hospital admission in type 2 diabetic patients aged 80 years or older. Exp Clin Endocrinol Diab 2010; 118: 215-219.
16. Shorr RI, Ray WA, Daugherty JR, Griffin MR. Incidence and risk factors for serious hypoglycemia in older persons using insulin or sulfonylureas. Arch Intern Med 1997; 157: 1681-1686.
17. Budnitz DS, Lovegrove MC, Shehab N, Richards CL. Emergency hospitalizations for adverse drug events in older Americans. N Engl J Med 2011; 365: 2002-2012.
18. Bertoni AG, Krop JS, Anderson GF, Brancati FL. Diabetes-related morbidity and mortality in a national sample of U.S. elders. Diabetes Care 2002; 25: 471-475.
19. Kirkman MS, Briscoe VJ, Clark N et al. Diabetes in older adults. Diabetes Care 2012; 35: 2650-2664.
20. Cukierman T, Gerstein HC, Williamson JD. Cognitive decline and dementia in diabetes-systematic overview of prospective observational studies. Diabetologia 2005; 48: 2460-2469.
21. Barzilai N, Guo H, Mahoney EM et al. Efficacy and tolerability of sitagliptin monotherapy in elderly patients with type 2 diabetes: a randomized, double-blind, placebo-controlled trial. Curr Med Res Opin 2011; 27: 1049-1058.
22. Schweizer A, Dejager S, Bosi E. Comparison of vildagliptin and metformin monotherapy in elderly patients with type 2 diabetes: a 24-week, double-blind, randomized trial. Diabetes Obes Metab 2009; 11: 804-812.
23. Rosenstock J, Wilson C, Fleck P. Alogliptin versus glipizide monotherapy in elderly type 2 diabetes patients with mild hyperglycemia: a prospective, double-blind, randomized, 1-year study. Diabetes Obes Metab 2013; 15: 906-914.
24. Strain WD, Lukashevich V, Kothny W, Hoellinger MJ, Paldanius PM. Individualised treatment targets for elderly patients with type 2 diabetes using vildagliptin add-on or lone therapy (INTERVAL): a 24 week, randomised, double-blind, placebo-controlled study. Lancet 2013; 382: 409-416.
25. Graefe-Mody U, Retlich S, Friedrich C. Clinical pharmacokinetics and pharmacodynamics of linagliptin. Clin Pharmacokinet 2012; 51: 411-427.
26. 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: 1413-1423.
27. Del Prato S, Barnett AH, Huisman H, Neubacher D, Woerle HJ, Dugi KA. Effect of linagliptin monotherapy on glycaemic control and markers of beta-cell function in patients with inadequately controlled type 2 diabetes: a randomized controlled trial. Diabetes Obes Metab 2011; 13: 258-267.
28. Taskinen MR, Rosenstock J, Tamminen I et al. 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.
29. 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: 1352-1361.
30. Yki-Jarvinen H, Durán-Garcia S, Pinnetti S et al. Efficacy and safety of linagliptin as add-on therapy to basal insulin in patients with type 2 diabetes. Diabetes 2012; 61(Suppl 1): A255.
31. McGill JB, Sloan L, Newman J et al. Long-term efficacy and safety of linagliptin in patients with type 2 diabetes and severe renal impairment: a 1-year, randomized, double-blind, placebo-controlled study. Diabetes Care 2013; 36: 237-244.
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: 565-574.
33. Schernthaner G, Barnett AH, Emser A et al. Safety and tolerability of linagliptin: a pooled analysis of data from randomized controlled trials in 3572 patients with type 2 diabetes mellitus. Diabetes Obes Metab 2012; 14: 470-478.
34. Inzucchi S, Nauck M, von Eynatten M, Hehnke U, Woerle H-J, Henry R. Lower Risk of Hypoglycemia in Elderly Type 2 Diabetes Patients when Linagliptin was Added to Basal Insulin: An Exploratory Analysis. Chicago: American Diabetes Association Scientific Sessions, 2013.
35. Munshi MN, Segal AR, Suhl E et al. Frequent hypoglycemia among elderly patients with poor glycemic control. Arch Intern Med 2011; 171: 362-364.
36. Seaquist ER, Anderson J, Childs B et al. Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association and the Endocrine Society. Diabetes Care 2013; 36: 1384-1395.
37. Groop PH, Cooper ME, Perkovic V, Emser A, Woerle HJ, von Eynatten M. Linagliptin lowers albuminuria on top of recommended standard treatment in patients with type 2 diabetes and renal dysfunction. Diabetes Care 2013: 3460-3468.
38. Johansen OE, Neubacher D, von Eynatten M, Patel S, Woerle HJ. Cardiovascular safety with linagliptin in patients with type 2 diabetes mellitus: a pre-specified, prospective, and adjudicated meta-analysis of a phase 3 programme. Cardiovasc Diabetol 2012; 11: 3.
39. Marx N, Rosenstock J, Kahn SE et al. Baseline characteristics of participants enrolled in the cardiovascular outcome study of linagliptin versus glimepiride in early type 2 diabetes (CAROLINA). Diabetologia 2013; 56(Suppl 1): S36.